241 research outputs found
COVID-19 research in critical care: the good, the bad, and the ugly
The extraordinary pace of research on coronavirus disease
2019 (COVID-19) has been one of the major success
stories of the pandemic. Therapeutic trials involving
thousands of patients, which usually take years to complete,
have been reported in a matter of months. National
and international registries and networks have reported
on tens of thousands of patients in near real time. However,
there have also been many challenges: hundreds of
trials have been underpowered, duplicated, or of poor
quality; excessive bureaucracy has complicated study initiation;
and only a small percentage of eligible patients
worldwide have been enrolled in studies, while many
others have been treated with off-label, unproven therapies.
All of this has been complicated by an âinfodemicâ
of low-quality medical information, accelerated by social
media.info:eu-repo/semantics/publishedVersio
Dinosolve: a protein disulfide bonding prediction server using context-based features to enhance prediction accuracy
Nature inspired meta-heuristic algorithms for deep learning: recent progress and novel perspective
Deep learning is presently attracting extra ordinary attention from
both the industry and the academia. The application of deep learning in computer
vision has recently gain popularity. The optimization of deep learning models
through nature inspired algorithms is a subject of debate in computer science. The
application areas of the hybrid of natured inspired algorithms and deep learning
architecture includes: machine vision and learning, image processing, data science,
autonomous vehicles, medical image analysis, biometrics, etc. In this paper,
we present recent progress on the application of nature inspired algorithms in
deep learning. The survey pointed out recent development issues, strengths,
weaknesses and prospects for future research. A new taxonomy is created based
on natured inspired algorithms for deep learning. The trend of the publications in
this domain is depicted; it shows the research area is growing but slowly. The
deep learning architectures not exploit by the nature inspired algorithms for
optimization are unveiled. We believed that the survey can facilitate synergy
between the nature inspired algorithms and deep learning research communities.
As such, massive attention can be expected in a near future
Burden-driven feedback control of gene expression
Cells use feedback regulation to ensure robust growth despite fluctuating demands for resources and differing environmental conditions. However, the expression of foreign proteins from engineered constructs is an unnatural burden that cells are not adapted for. Here we combined RNA-seq with an in vivo assay to identify the major transcriptional changes that occur in Escherichia coli when inducible synthetic constructs are expressed. We observed that native promoters related to the heat-shock response activated expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a dCas9-based feedback-regulation system that automatically adjusts the expression of a synthetic construct in response to burden. Cells equipped with this general-use controller maintained their capacity for native gene expression to ensure robust growth and thus outperformed unregulated cells in terms of protein yield in batch production. This engineered feedback is to our knowledge the first example of a universal, burden-based biomolecular control system and is modular, tunable and portable
The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis
DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect of M. bovis infection on the bAM DNA methylome. The methylomes of bAM infected with M. bovis were compared to those of non-infected bAM 24âhours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33-66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM
Increased sleep duration precedes the improvement of other symptom domains during the treatment of acute mania: a retrospective chart review
In Vitro Transformation of Primary Human CD34+ Cells by AML Fusion Oncogenes: Early Gene Expression Profiling Reveals Possible Drug Target in AML
Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of 4 major groups of AML fusion oncogenes on primary human CD34+ cells. As expected from their clinical similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They both caused erythroid hyperplasia and a clear block in erythroid and myeloid maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a dramatic increase in long-term proliferation and self-renewal. Gene expression profiling revealed two distinct temporal patterns of gene deregulation. Gene deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA occurred within 6 hours, followed by a dramatic drop in the numbers of deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1-ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53, specifically inhibited the proliferation and self-renewal of primary human CD34+ cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in cell transformation by AML1-ETO. These data show that differences among AML fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells and that early gene expression profiling in these cells can reveal potential drug targets in AML
Global economic burden of unmet surgical need for appendicitis
Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US 73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was 75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially
Lower versus higher dose of enteral caloric intake in adult critically ill patients: a systematic review and meta-analysis
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