Search results for "random"
showing 10 items of 3931 documents
A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests
2021
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 t…
Polyvascular disease: A narrative review of current evidence and a consideration of the role of antithrombotic therapy.
2020
Abstract Background and aims Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. Methods MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with c…
Two-Stage Bayesian Approach for GWAS With Known Genealogy
2019
Genome-wide association studies (GWAS) aim to assess relationships between single nucleotide polymorphisms (SNPs) and diseases. They are one of the most popular problems in genetics, and have some peculiarities given the large number of SNPs compared to the number of subjects in the study. Individuals might not be independent, especially in animal breeding studies or genetic diseases in isolated populations with highly inbred individuals. We propose a family-based GWAS model in a two-stage approach comprising a dimension reduction and a subsequent model selection. The first stage, in which the genetic relatedness between the subjects is taken into account, selects the promising SNPs. The se…
Alternative Splice Forms of CYLD Mediate Ubiquitination of SMAD7 to Prevent TGFB Signaling and Promote Colitis
2018
Background & Aims The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosus, and variants have been associated with Crohn disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined the expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. Methods We performed immunohistochemical analyses of colon tissues from patients with untreated CD and patients without inflammatory bowel diseases (controls). We obtained mice that expressed splice forms of CYLD (sCYLD mice) without or with SMAD7 (sCYLD/SMAD7 mice) from tr…
Quality and antioxidant response of gilthead seabream (Sparus aurata L.) to dietary supplements of fenugreek (Trigonella foenum graecum) alone or com…
2017
The present study was conducted to determine the potential effect of the dietary intake of fenugreek (Trigonella foenum graecum) seeds alone or in combination with Bacillus licheniformis, Lactobacillus plantarum or B. subtilis on gilthead seabream quality and antioxidant response after 2 and 3 weeks of experimental feeding. The results showed that the supplements did not affect the percentage of the fatty acid profiles of muscle, demonstrating that all the additives tested can be administrated without any negative effect on biochemical composition and quality of gilthead seabream. The quantification of thiobarbituric acid reactive substances in muscle demonstrated the significant beneficial…
Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.
2017
Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects …
Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects
2020
Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxi…
Expanding role of cytomegalovirus as a human pathogen
2016
Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality in transplant recipients, despite major advancements in preventative strategies. Antiviral prophylaxis and pre-emptive antiviral therapeutic regimens are associated with a high incidence of late-onset end-organ disease and cause drug-related toxicity when overused. Therefore, the identification of risk factors for CMV replication is required. Genetic and immunological factors that predispose individuals to CMV-related clinical complications have been identified and may be instrumental for optimizing CMV treatment in the future. Evidence suggests a causal pathogenetic link between CMV-related complications and i…
The effect of a membrane-mimicking environment on the interactions of Cu2+ with an amyloidogenic fragment of chicken prion protein
2017
Prion proteins (PrP) from different species have the ability to tightly bind Cu2+ ions. Copper coordination sites are located in the disordered and flexible N-terminal region which contains several His anchoring sites. Among them, two His residues are found in the so called amyloidogenic PrP region which is believed to play a key role in the process leading to oligomer and fibril formation. Both chicken and human amyloidogenic regions have a hydrophobic C-terminal region rich in Ala and Val amino acids. Recent findings revealed that this domain undergoes random coil to α-helix structuring upon interaction with membrane models. This interaction might strongly impact metal binding abilities e…
Molecular Diversity Required for the Formation of Autocatalytic Sets
2019
Systems chemistry deals with the design and study of complex chemical systems. However, such systems are often difficult to investigate experimentally. We provide an example of how theoretical and simulation-based studies can provide useful insights into the properties and dynamics of complex chemical systems, in particular of autocatalytic sets. We investigate the issue of the required molecular diversity for autocatalytic sets to exist in random polymer libraries. Given a fixed probability that an arbitrary polymer catalyzes the formation of other polymers, we calculate this required molecular diversity theoretically for two particular models of chemical reaction systems, and then verify …