The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to ...randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T.
Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence.
Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (
= .74 and
= .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (
= .63) or the number of MS lesions (
= .15).
With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.
Hepatopulmonary syndrome Sayadi, A; Duhaut, L; Robert, F ...
La revue de medecine interne
45, Številka:
3
Journal Article
Recenzirano
The hepatopulmonary syndrome (HPS) is one of the lung diseases associated with cirrhosis and portal hypertension. It should be discussed for any dyspnea in cirrhotic patients. HPS is a pulmonary ...vascular disease characterized by intrapulmonary vascular dilatations (IPVD). The pathogenesis is complex and seems to rely on communications between the portal and pulmonary circulations. The diagnosis is based on a triad of liver disease and portal hypertension, evidence of IPVDs, and impaired gas exchange (alveolar-arterial oxygen difference A-aO
≥15mmHg). HPS impairs prognosis (23% survival at 5years) and patients' quality of life. Liver transplantation (LT) allows regression of IPDVD in almost 100% of cases, normalization of gas exchange and improves survival with a 5-year post-LT survival between 76 and 87%. It is the only curative treatment, indicated in patients with severe HPS, defined by an arterial partial pressure of oxygen (PaO
) below 60mmHg. When LT is not indicated or feasible, long-term oxygen therapy may be proposed as a palliative treatment. A better understanding of the pathophysiological mechanisms is needed to improve the therapeutic possibilities in a near future.
The seed beetle Callosobruchus maculatus is a significant agricultural pest and increasingly studied model of sexual conflict. Males possess genital spines that increase the transfer of seminal fluid ...proteins (SFPs) into the female body. As SFPs alter female behaviour and physiology, they are likely to modulate reproduction and sexual conflict in this species. Here, we identified SFPs using proteomics combined with a de novo transcriptome. A prior 2D‐sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis identified male accessory gland protein spots that were probably transferred to the female at mating. Proteomic analysis of these spots identified 98 proteins, a majority of which were also present within ejaculates collected from females. Standard annotation workflows revealed common functional groups for SFPs, including proteases and metabolic proteins. Transcriptomic analysis found 84 transcripts differentially expressed between the sexes. Notably, genes encoding 15 proteins were highly expressed in male abdomens and only negligibly expressed within females. Most of these sequences corresponded to ‘unknown’ proteins (nine of 15) and may represent rapidly evolving SFPs novel to seed beetles. Our combined analyses highlight 44 proteins for which there is strong evidence that they are SFPs. These results can inform further investigation, to better understand the molecular mechanisms of sexual conflict in seed beetles.
The MDS1 and ecotropic viral integration site 1 (EVI1) complex locus (MECOM) gene encodes several transcription factor variants including MDS1-EVI1, EVI1 and EVI1Δ324. Although MDS1-EVI1 has been ...associated with tumor-suppressing activity, EVI1 is a known oncogene in various cancers, whose expression is associated with poor patient survival. Although EVI1Δ324 is co-transcribed with EVI1, its activity in cancer cells is not fully understood. Previous reports described that unlike EVI1, EVI1Δ324 protein cannot transform fibroblasts because of its disrupted N-terminal zinc finger (ZNF) domain. To better understand EVI1Δ324 biology and function, we obtained genome-wide binding occupancies and expression data in ovarian cancer cells. We characterized its DNA-binding sites, binding motif and target genes. Comparative analyses with previous study show that EVI1 and EVI1Δ324 share similar transcriptional activities linked to their common C-terminus ZNF domain. They bind to an E-twenty-six family (ETS)-like motif, target to a large extent the same genes and cooperate with AP1 transcription factor. EVI1Δ324-occupied genes were 70.7% similar to EVI1-bound genes. More strikingly, EVI1 and EVI1Δ324 differentially expressed genes were 99.87% identical, indicating comparable transcriptional regulatory functions. Consistently with gene ontologies linked to these target genes, EVI1Δ324 expression in HeLa cells could enhance anchorage-independent growth, such as EVI1, showing that EVI1Δ324 expression also lead to pro-oncogenic effects. The main specific feature of EVI1 variant is its N-terminus ZNF domain that binds DNA through GATA-like motif. We found that most GATA-like EVI1 chromatin immunoprecipitation sequencing peaks are far from genes and are not involved in transcriptional regulation. These genomic regions were enriched in simple sequence repeats and displayed high meiotic recombination rates. Overall, our genomics analyses uncovered common and specific features of two major MECOM isoforms. Their influence on transcription and downstream cell proliferation was comparable. However, EVI1-specific GATA-like binding sites, from its N-terminus ZNF domain, associated with high recombination rates, suggesting possible additional oncogenic potential for EVI1 in modulating genomic stability.
The MDS1 and ecotropic viral integration site 1 (EVI1) complex locus (MECOM) gene encodes several transcription factor variants including MDS1-EVI1, EVI1 and EVI1 Delta 324. Although MDS1-EVI1 has ...been associated with tumor-suppressing activity, EVI1 is a known oncogene in various cancers, whose expression is associated with poor patient survival. Although EVI1 Delta 324 is co-transcribed with EVI1, its activity in cancer cells is not fully understood. Previous reports described that unlike EVI1, EVI1 Delta 324 protein cannot transform fibroblasts because of its disrupted N-terminal zinc finger (ZNF) domain. To better understand EVI1 Delta 324 biology and function, we obtained genome-wide binding occupancies and expression data in ovarian cancer cells. We characterized its DNA-binding sites, binding motif and target genes. Comparative analyses with previous study show that EVI1 and EVI1 Delta 324 share similar transcriptional activities linked to their common C-terminus ZNF domain. They bind to an E-twenty-six family (ETS)-like motif, target to a large extent the same genes and cooperate with AP1 transcription factor. EVI1 Delta 324-occupied genes were 70.7% similar to EVI1-bound genes. More strikingly, EVI1 and EVI1 Delta 324 differentially expressed genes were 99.87% identical, indicating comparable transcriptional regulatory functions. Consistently with gene ontologies linked to these target genes, EVI1 Delta 324 expression in HeLa cells could enhance anchorage-independent growth, such as EVI1, showing that EVI1 Delta 324 expression also lead to pro-oncogenic effects. The main specific feature of EVI1 variant is its N-terminus ZNF domain that binds DNA through GATA-like motif. We found that most GATA-like EVI1 chromatin immunoprecipitation sequencing peaks are far from genes and are not involved in transcriptional regulation. These genomic regions were enriched in simple sequence repeats and displayed high meiotic recombination rates. Overall, our genomics analyses uncovered common and specific features of two major MECOM isoforms. Their influence on transcription and downstream cell proliferation was comparable. However, EVI1-specific GATA-like binding sites, from its N-terminus ZNF domain, associated with high recombination rates, suggesting possible additional oncogenic potential for EVI1 in modulating genomic stability.
Open-pit mining method has severe environmental impacts which should be prevented, monitored, controlled, and reduced by mined-land reclamation process. After mine closure, a permanent post-mining ...land use should be implemented as an appropriate choice for using different sections of mined land. The most appropriate alternative of post-mining land use for each section of mined land is presented as the optimum post-mining land use. Pit area among different sections of mined land has more significant effects on the environment and also on defining the optimum post-mining land use for other sections of mined land. Though there are several alternatives and criteria for defining the optimum post-mining land use, the multi-attribute decision-making methods can be efficient techniques in this regard. The nature of the effective parameters used for defining the optimum post-mining land use is the same as Fuzzy numbers including incremental changes without definite limits. Thus, application of the Fuzzy multi-attribute decision-making modeling can produce more reliable results than that of other techniques. As well, pair-wise comparisons and judgments through Fuzzy numbers have proper consistency with the nature of the effective parameters; therefore, a model is developed to attain the optimum post-mining land use for pit area through Fuzzy analytical hierarchy processing. As a case study, the model was implemented in Sungun copper mine in the Northwest of Iran. Forestry–lumber production was defined as the optimum post-mining land use containing the greatest relative importance coefficient 3.019 for the pit area in this mine.
The stoichiometry of ethanol oxidation (average number of electrons transferred per molecule) is a crucial parameter in fundamental studies of ethanol oxidation and the development of direct ethanol ...fuel cells and electrolysis cells. Measurements of stoichiometry are particularly important at elevated temperatures, where these cells become more efficient. In this work, rotating disk and flow cell methods have been used to explore the temperature dependence of ethanol oxidation at Pt/C and PtRu/C electrodes. Stoichiometries determined from the slopes of Koutecky–Levich plots ranged from 2.1 to 2.8 at 24 °C and increased to a range of 3.4 to 5.6 at 80 °C. They were higher for PtRu/C, and increased more with increasing temperature. At 80 °C, there was a significant decrease in stoichiometry with increasing potential at both catalysts, indicating a decrease in selectivity for the complete oxidation of ethanol to CO
2
. Analysis of ethanol consumption and product distributions using a flow cell provided independent measurements of stoichiometry that were in reasonable agreement with values from Koutecky–Levich plots.
PurposeLupus nephritis (LN) is a major clinical challenge and cause of significant morbidity and mortality in systemic lupus erythematosus (SLE). Today >180 SLE risk loci at Genome-wide significance ...(GWS, p < 5×10–8), including risk genes involved in B-cell function, have been identified. Associations between an individual’s genetical burden and clinical manifestations in SLE can be studied using a polygenic risk score (PRS). In this study, we investigated associations between two SLE B-cell PRSs, SLE ACR-82 classification criteria, dsDNA antibodies and LN.MethodsFemale SLE patients (n=1256) and healthy controls (n=519) from Scandinavia were genotyped using Illumina’s Global Screening Array. Two PRSs were calculated1 for each individual, one including 21 GWS risk loci for SLE in genes assigned to B-cell related pathways (SLE B-cell PRS) according to the Kyoto encyclopedia of genes and genomes, Gene Ontology and Reactome databases, and one including a subset of 12 of these loci, limited to B-cell activation pathways (SLE B-cell activation PRS). High and low PRSs were defined as PRSs in the highest quartile and in quartile 1–3, respectively, and groups were compared by logistic regression (SPSS, version 28.0.1.0). A p-value < 0.05 was considered significant.ResultsIn total, 30% of patients had nephritis according to the ACR-82 criteria with an average age at nephritis onset of 33 years and dsDNA antibodies were more prevalent among patients with nephritis (78%) compared with patients without nephritis (56%) (OR 2.8 (2.0–3.9), p=2.1×10–10). The mean SLE B-cell PRS was higher in cases 2.9 (2.9–3.0) than controls 2.7 (2.6–2.7), (p = 4.1×10–11) and 11% of patients had an SLE B-cell PRS above the 95th percentile of controls. SLE was more prevalent in individuals with a high compared with a low SLE B-cell PRS (OR 1.8 (1.4–2.4), p=4.0×10–6).The immunological criterion (ACR-82) was more prevalent among patients with a high compared with low SLE B-cell PRS (OR 1.4 (1.1–1.9), p = 0.013) and a similar association was found for dsDNA antibodies (OR 1.5 (1.1–2.0), p = 0.017). Numerically, a higher prevalence of nephritis was observed in patients with high compared with low SLE B-cell PRS, but it did not reach statistical significance (OR 1.2 (0.9–1.6), p = 0.19). However, the prevalence of nephritis was higher in patients with a high compared with a low SLE B-cell activation PRS (OR 1.3 (1.0–1.8), p = 0.039), Figure 1.Abstract PO.4.94 Figure 1Prevalence of nephritis in patients with a B-cell activation PRS above the third quartile compared with patients in lower quartilesConclusionsHigh SLE polygenic risk related to B cell function is associated with development of dsDNA antibodies and nephritis in SLE. Assessing B-cell PRSs can be important in order to determine the immunologic pathways influencing the disease and to predict clinical phenotype.ReferencesReid, S. et al. High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Ann Rheum Dis 2020;79, 363–369.
PurposeLupus nephritis (LN) is a major cause of morbidity in Systemic Lupus Erythematosus (SLE) and a subset of patients still develop end stage renal disease (ESRD). Genetics is important in SLE ...pathogenesis and today >180 SLE risk loci have been identified at Genome-wide significance (GWS). Here we investigate how gene-gene interactions influence the risk of WHO class III or IV LN in patients with SLE.MethodsPatients with SLE from Sweden and Norway (n=1455) were genotyped with Illumina’s Global Screening Array. Clinical information was retrieved from medical charts, including kidney biopsy data classified according to the WHO. Eleven SLE GWS risk single nucleotide polymorphisms (SNPs) were analyzed regarding gene-gene interaction for LN; ITGAM, IRF5, STAT4, IL12A, TYK2, PTPN22, TNFSF4, BANK1, BLK, and two tag SNPs for HLA-DRB1*03:01 and HLA-DRB1*15:01. Data was analyzed using cox regression and logistic regression including the individual SNPs, sex and SLE duration as covariates (SPSS version 28.0.1.0 (142)). P-value < 0.05 was considered significant.ResultsIn total, 33% (476/1455) of patients had a history of LN, according to the ACR-82 criteria, with an average age at onset of 33 years. Kidney biopsy data was available for 301 patients and 65% (197/301) of the biopsies showed WHO class III or IV LN. Comparing patients with class III/IV LN with non-nephritis patients, we identified a significant interaction between the HLA-DRB1*03:01 and STAT4 risk alleles (OR 3.4 (1.4–8.3), p= 0.009 for 3 risk variants and OR 9.1 (1.1–73), p= 0.037 for 4 risk variants), Table 1. An interaction was also observed when including patients with 3 or 4 risk variants as one group in a model (OR 3.3 (1.4–8.0), p= 0.008). The prevalence of class III/IV LN in patients with 3–4 risk variants was 30% (24/81) compared with 16% (166/1059) in patients with 0–2 risk variants, p = 0.001. Furthermore, patients with 3–4 risk alleles displayed a decreased time from SLE diagnosis to the onset of class III/IV LN (HR 2.6 (1.1–5.8), p= 0.022) compared with patients with 0–2 risk alleles. Finally, when analyzing the 2 SNPs separately for association with class III/IV LN, no association was observed for STAT4, but patients homozygous for the HLA-DRB1*03:01 tag risk allele had an increased risk (OR 1.9 (1.0–3.5), p= 0.036).Abstract S10.2 Table 1Logistic regression. WHO class III/IV nephritis vs. non-nephritisConclusionsAn interaction between HLA-DRB1*03:01 and STAT4 risk gene variants increase the risk of WHO class III and IV LN in SLE. The results indicate an importance of gene-gene interaction for LN development and a potential role of interactions between genes in SLE pathogenesis.
Net present value (NPV) is the most popular economic indicator in evaluation of the investment projects. For the mining projects, this criterion is calculated under uncertainty associated with the ...relevant parameters of say commodity price, discount rate, etc. Accurate prediction of the NPV is a quite difficult process. This paper mainly deals with the development of a new model to predict NPV using artificial neural network (ANN) in the Zarshuran gold mine, Iran. Gold price (as the main product), silver price (as the byproduct), and discount rate were considered as input parameters for the ANN model. To reach an optimum architecture, different types of networks were examined on the basis of a trial and error mechanism. A neural network with architecture 3-15-10-1 and root mean square error of 0.092 is found to be optimum. Prediction capability of the proposed model was examined through computing determination coefficient (
R
2
= 0.987) between predicted and real NPVs. Absolute error of US$0.1 million and relative error of 1.4 % also confirmed powerfulness of the developed ANN model. According to sensitivity analysis, it was observed that the gold price is the most effective and discount rate is the least effective parameter on the NPV.
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