Search results for "GIS"
showing 10 items of 7190 documents
Dual inhibitors of histone deacetylases and other cancer-related targets: A pharmacological perspective.
2020
International audience; Epigenetic enzymes histone deacetylases (HDACs) are clinically validated anticancer drug targets which have been studied intensively in the past few decades. Although several drugs have been approved in this field, they are still limited to a subset of hematological malignancies (in particular T-cell lymphomas), with therapeutic potential not fully realized and the drug-resistance occurred after a certain period of use. To maximize the therapeutic potential of these classes of anticancer drugs, and to extend their application to solid tumors, numerous combination therapies containing an HDACi and an anticancer agent from other mechanisms are currently ongoing in clin…
Parental risk factors of anorectal malformations: Analysis with a regional population-based control group
2015
BACKGROUND Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational diabetes, chronic cardiovascular and respiratory diseases, periconceptional folic acid and multivitamin intake. METHODS Data from the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared with data from the Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg, Germany. Controls were matched to cases by gender and birth year of the child. Crude and adjusted odds ratios (95% confidence intervals) were calculated f…
Applications of Chemoinformatics in Predictive Toxicology for Regulatory Purposes, Especially in the Context of the EU REACH Legislation
2018
Chemoinformatics methodologies such as QSAR/QSPR have been used for decades in drug discovery projects, especially for the finding of new compounds with therapeutic properties and the optimization of ADME properties on chemical series. The application of computational techniques in predictive toxicology is much more recent, and they are experiencing an increasingly interest because of the new legal requirements imposed by national and international regulations. In the pharmaceutical field, the US Food and Drug Administration (FDA) support the use of predictive models for regulatory decision-making when assessing the genotoxic and carcinogenic potential of drug impurities. In Europe, the REA…
Integrative analysis of structural variations using short-reads and linked-reads yields highly specific and sensitive predictions.
2020
Genetic diseases are driven by aberrations of the human genome. Identification of such aberrations including structural variations (SVs) is key to our understanding. Conventional short-reads whole genome sequencing (cWGS) can identify SVs to base-pair resolution, but utilizes only short-range information and suffers from high false discovery rate (FDR). Linked-reads sequencing (10XWGS) utilizes long-range information by linkage of short-reads originating from the same large DNA molecule. This can mitigate alignment-based artefacts especially in repetitive regions and should enable better prediction of SVs. However, an unbiased evaluation of this technology is not available. In this study, w…
Multidimensional frailty increases cardiovascular risk in older people: An 8-year longitudinal cohort study in the Osteoarthritis Initiative.
2021
Background:\ud \ud Cardiovascular diseases (CVDs) are the most important cause of mortality and an important cause of disability. Frailty seems to be associated with higher cardiovascular risk, but limited research has been done using a multidimensional approach to frailty. Thus, the present study aimed to investigate whether the multidimensional prognostic index (MPI), based on comprehensive geriatric assessment (CGA), is associated with CVD risk in the Osteoarthritis Initiative (OAI) study.\ud \ud Methods:\ud \ud Community-dwellers affected by knee OA or at high risk for this condition were followed for 8 years. A standardized CGA including information on functional, nutritional, mood, co…
Trace elements levels in centenarian ‘dodgers’
2016
Trace element bioavailability can play a role in several metabolic and physiological pathways known to be altered during the aging process. We aimed to explore the association of trace elements with increased lifespan by analyzing the circulating levels of seven trace elements (Cr, Cu, Fe, Mn, Mo, Se and Zn) in a cohort of healthy centenarians or ‘dodgers’ (≥100 years, free of major age-related diseases) in comparison with sex-matched younger elderly controls. Centenarians showed significant lower Cu (783.7 (76.7, 1608.9) vs 962.5 (676.3, 2064.4) μg/mL, P < 0.001), but higher Fe (1.3 (0.4, 4.7) vs 1.1 (0.5, 8.4) μg/mL, P = 0.003) and Se (85.7 (43.0, 256.7) vs 77.8 (24.3, 143.8) ng/mL, P = 0…
What drives athletes toward dietary supplement use: objective knowledge or self-perceived competence? Cross-sectional analysis of professional team-s…
2019
Background Issues related to knowledge of nutrition and dietary supplementation (DS) are understudied in professional athletes. This study aimed to examine the possible association between knowledge of nutrition and DS (KN&DS) and dietary supplement use (DSU) among professional athletes involved in team sports. Methods The sample comprised professional team-sport athletes (N = 912, age: 22.11 ± 3.37 years, 356 females) involved in four Olympic sports: basketball (N = 228), soccer (N = 324), volleyball (N = 154), and handball (N = 206). The participants were tested by previously validated questionnaires to examine their self-perceived competence on nutrition and DS (S/KN&DS), their objective…
Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency
2017
Disclaimer: This diagnostic guideline is intended as an educational resource and represents the opinions of the authors, and is not representative of recommendations or policy of the American College of Medical Genetics and Genomics (ACMG). The information should be considered a consensus based on expert opinion, as more comprehensive levels of evidence were not available in the literature in all cases. Background: Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and often fatal lysosomal storage disease. The underlying metabolic defect is deficiency of the enzyme acid sphingomyelinase that results in progressive accumulation of sphingomyelin in target tissues. ASMD manifests…
Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015
2020
The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analyse…
Association between γ marker, human leucocyte antigens and killer immunoglobulin‐like receptors and the natural course of human cytomegalovirus infec…
2017
Natural killer (NK) cells provide a major defence against cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. Also GM allotypes, able to influence the NK antibody-dependent cell-mediated cytotoxicity (ADCC), appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA. In the present report, with the aim to gain insight into the immune mechanisms controlling HCMV, we have studied t…