World Health Organization Grade II/III Glioma Molecular Status: Prediction by MRI Morphologic Features and Apparent Diffusion Coefficient

BACKGROUND: A readily implemented MRI biomarker for glioma genotyping is currently lacking. PURPOSE: To evaluate clinically available MRI parameters for predicting isocitrate dehydrogenase (IDH) status in patients with glioma. MATERIALS AND METHODS: In this retrospective study of patients studied from July 2008 to February 2019, untreated World Health Organization (WHO) grade II/III gliomas were analyzed by three neuroradiologists blinded to tissue results. Apparent diffusion coefficient (ADC) minimum (ADC_{mi}) and mean (ADC_{mean}) regions of interest were defined in tumor and normal appearing white matter (ADC_{NAWM}). visual rating of anatomic features (T1 weighted, T1 weighted with contrast enhancement, T2 weighted, and fluid-attenuated inversion recovery) was performed. Interobserver comparison (intraclass correlation coefficient and Cohen κ) was followed by nonparametric (Kruskal-Wallis analysis of variance) testing of associations between ADC metrics and glioma genotypes, including Bonferroni correction for multiple testing. Descriptors with sufficient concordance (intraclass correlation coefficient, >0.8; κ > 0.6) underwent univariable analysis. Predictive variables (P < .05) were entered into a multivariable logistic regression and tested in an additional test sample of patients with glioma. RESULTS: he study included 290 patients (median age, 40 years; interquartile range, 33–52 years; 169 male patients) with 82 IDH wild-type, 107 IDH mutant/1p19q intact, and 101 IDH mutant/1p19q codeleted gliomas. Two predictive models incorporating ADC_{mean}-to-ADC_{NAWM} ratio, age, and morphologic characteristics, with model A mandating calcification result and model B recording cyst formation, classified tumor type with areas under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.91, 0.97) and 0.96 (95% CI: 0.93, 0.98), respectively. In the test sample of 49 gliomas (nine IDH wild type, 21 IDH mutant/1p19q intact, and 19 IDH mutant/1p19q codeleted), the classification accuracy was 40 of 49 gliomas (82%; 95% CI: 71%, 92%) for model A and 42 of 49 gliomas (86%; 95% CI: 76%, 96%) for model B. CONCLUSION: Two algorithms that incorporated apparent diffusion coefficient values, age, and tumor morphologic characteristics predicted isocitrate dehydrogenase status in World Health Organization grade II/III gliomas on the basis of standard clinical MRI sequences alone

Acute torsion of the gallbladder: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The relation between the producer and consumer price indices: a two-country study

© 2017, Macmillan Publishers Ltd., part of Springer Nature. Marketing managers are often in a dilemma about which pricing index to rely on while calculating the annual increase in the prices for their product. To provide insights that can reduce this dilemma, a critical comparison of the Producer Price index and consumer price index is called for. In this study, the relation between the Producer Price Index (PPI) and Consumer Price Index (CPI) was investigated through a comparison between Turkey and UK. Unlike many other previous studies, this study tried to determine the dominant pricing approach in an economy by examining the relation between the producer and consumer prices. In this context, VAR, impulse-response, variance decomposition, and Granger causality tests were used for the analyses of time series data. The results of study showed that there was bidirectional causality between the producer and consumer prices in both countries. Therefore, it was asserted that businesses in both countries generally apply mixed pricing approach. The results thus provide some interesting insights that can aid marketing managers in their pricing decisions

Diversity of Protein and mRNA Forms of Mammalian Methionine Sulfoxide Reductase B1 Due to Intronization and Protein Processing

Background: Methionine sulfoxide reductases (Msrs) are repair enzymes that protect proteins from oxidative stress by catalyzing stereospecific reduction of oxidized methionine residues. MsrB1 is a selenocysteine-containing cytosolic/nuclear Msr with high expression in liver and kidney. Principal Findings: Here, we identified differences in MsrB1 gene structure among mammals. Human MsrB1 gene consists of four, whereas the corresponding mouse gene of five exons, due to occurrence of an additional intron that flanks the stop signal and covers a large part of the 3′-UTR. This intron evolved in a subset of rodents through intronization of exonic sequences, whereas the human gene structure represents the ancestral form. In mice, both splice forms were detected in liver, kidney, brain and heart with the five-exon form being the major form. We found that both mRNA forms were translated and supported efficient selenocysteine insertion into MsrB1. In addition, MsrB1 occurs in two protein forms that migrate as 14 and 5 kDa proteins. We found that each mRNA splice form generated both protein forms. The abundance of the 5 kDa form was not influenced by protease inhibitors, replacement of selenocysteine in the active site or mutation of amino acids in the cleavage site. However, mutation of cysteines that coordinate a structural zinc decreased the levels of 5 and 14 kDa forms, suggesting importance of protein structure for biosynthesis and/stability of these forms. Conclusions: This study characterized unexpected diversity of protein and mRNA forms of mammalian selenoprotein MsrB1

Dietary Restriction Depends on Nutrient Composition to Extend Chronological Lifespan in Budding Yeast Saccharomyces cerevisiae

10.1371/journal.pone.0064448PLoS ONE85

The Unfolded Protein Response Is Not Necessary for the G1/S Transition, but It Is Required for Chromosome Maintenance in Saccharomyces cerevisiae

BACKGROUND: The unfolded protein response (UPR) is a eukaryotic signaling pathway, from the endoplasmic reticulum (ER) to the nucleus. Protein misfolding in the ER triggers the UPR. Accumulating evidence links the UPR in diverse aspects of cellular homeostasis. The UPR responds to the overall protein synthesis capacity and metabolic fluxes of the cell. Because the coupling of metabolism with cell division governs when cells start dividing, here we examined the role of UPR signaling in the timing of initiation of cell division and cell cycle progression, in the yeast Saccharomyces cerevisiae. METHODOLOGY/PRINCIPAL FINDINGS: We report that cells lacking the ER-resident stress sensor Ire1p, which cannot trigger the UPR, nonetheless completed the G1/S transition on time. Furthermore, loss of UPR signaling neither affected the nutrient and growth rate dependence of the G1/S transition, nor the metabolic oscillations that yeast cells display in defined steady-state conditions. Remarkably, however, loss of UPR signaling led to hypersensitivity to genotoxic stress and a ten-fold increase in chromosome loss. CONCLUSIONS/SIGNIFICANCE: Taken together, our results strongly suggest that UPR signaling is not necessary for the normal coupling of metabolism with cell division, but it has a role in genome maintenance. These results add to previous work that linked the UPR with cytokinesis in yeast. UPR signaling is conserved in all eukaryotes, and it malfunctions in a variety of diseases, including cancer. Therefore, our findings may be relevant to other systems, including humans

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 &lt;/=16, 16-24, and &gt;24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients