30 research outputs found
Prenatal exposure of a girl with autism spectrum disorder to 'horsetail' (Equisetum arvense) herbal remedy and alcohol: a case report
Pan-cancer analysis of whole genomes
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
Cassava postharvest physiological deterioration: a complex phenomenon involving calcium signaling, reactive oxygen species and programmed cell death
Molecular characterization and protective efficacy of silent information regulator 2A from Eimeria tenella
How reproducible are surface areas calculated from the BET equation?
Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer-Emmett-Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro- and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This round-robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called "BET surface identification" (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible
Optimal switch location in mobile communication networks using hybrid genetic algorithms
The optimal positioning of switches in a mobile communication network is an
important task, which can save costs and improve the performance of the network.
In this paper we propose a model for establishing which are the best nodes of the
network for allocating the available switches, and several hybrid genetic algorithms
to solve the problem. The proposed model is based on the so called capacitated pmedian
problem, which have been previously tackled in the literature. This problem
can be split in two subproblems: the selection of the best set of switches, and a
terminal assignment problem to evaluate each selection of switches. The hybrid
genetic algorithms for solving the problem are formed by a conventional genetic
algorithm, with a restricted search, and several local search heuristics. In this work
we also develop novel heuristics for solving the terminal assignment problem in a fast
and accurate way. Finally, we show that our novel approaches, hybridized with the
genetic algorithm, outperform existing algorithms in the literature for the p-median
problem.This work has been partially
supported by a Universidad de Alcal´a project number UAH-PI2005/019. X.
Yao’s work has been partially supported by a National Natural Science Foundation
of China grant, number 60428202
NMR assignment of actin depolymerizing and dynamics regulatory protein from Leishmania donovani
Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial
Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) ‘‘A way to make Europe’’ and supported by SCReN (Spanish Clinical Research Network), ISCIII, project PT17/0017/0009. Clinical trial insurance coverage was kindly donated by MARCH RS Correduría de Seguros y Reaseguros. Mikel Mancheño-Losa holds a "Río Hortega" research contract (expte. CM19/00226N
Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: study protocol of a cluster randomized trial
10.1186/s13063-022-06293-xTrials231479