12 research outputs found

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    Inhibition of mild steel corrosion in HCI solution using chitosan

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    The efficiency of chitosan (a naturally occurring polymer) as a corrosion inhibitor for mild steel in 0.1 M HCl, was investigated by gravimetric, electrochemical and spectroscopic measurements (SEM observations and UV-visible analysis). The polymer was found to inhibit corrosion even at a very low concentration. Inhibition efficiency increases with a rise in temperature up to 96 % at 60°C and then drops to 93% at 70°C, while it slightly increases with an increase in chitosan concentration. Polarization curves indicate that chitosan functions as a mixed inhibitor, affecting both cathodic and anodic corrosion reactions. Impedance results indicate that chitosan was adsorbed on the metal/solution interface. Adsorption of chitosan at the mild steel surface is found to be in agreement with Langmuir adsorption isotherm model. Chemical adsorption is the proposed mechanism for corrosion inhibition considering the trend of protection efficiency with temperature. Calculated kinetic and thermodynamic parameters corroborate the proposed mechanism.Fil: Umoren, Saviour E.. University of Uyo. Faculty of Science; Nigeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Banera, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Alonso Garcia, Teodoro. Biosurfaces Unit, Cic BIOMAGUNE; EspañaFil: Gervasi, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Mirifico, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; Argentin

    Recent Advances in Sugarcane Industry Solid By-Products Valorization

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    Sugarcane is among the leading agricultural crop cultivated in tropical regions of the world. Industrial processing of sugarcane generates sugar; as well as various solid wastes (i.e. sugarcane bagasse, pressmud). Improvement of biotechnology in industrial level, offers opportunities for economic utilization of these solid residues. In the last few decades, sugarcane bagasse and pressmud have been explored in the theme of lignocellulosic bioconversion. The recalcitrance of biomass is a major drawback towards successful exploitation of lignocellulosic residues. Pretreatment by suitable/efficient processes can overcome this limitation. In this regards; physical, chemical and biological treatment systems are brought into our perspective. Chemical and physicochemical methods are capital-intensive but not environment-friendly, in contrast, method like biological treatment is eco-friendly but extremely slow. There are still major technological and economic challenges need to be addressed; e.g. bioprospecting, established more reliable genetically modified microorganisms, upgrade gene cloning and sequencing processes, yield improvement at large scale etc. Productions of value-added products from these solid wastes are discussed in such a way that pinpoints the most recent trends and the future directions. Biofuels, enzymes, organic acids and bio-sorbents production draw a clear sketch of the current and future bio-based products. Nano-biotechnology and genetic engineering could be future trends to improved processes and products. This review serves as a valuable reference material for a wide range of scientists and technologists in the relevant fields

    Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors

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    HOW DO ANIMAL DNA VIRUSES GET TO THE NUCLEUS?

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    The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

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