An automatic deep learning-based workflow for glioblastoma survival prediction using pre-operative multimodal MR images

We proposed a fully automatic workflow for glioblastoma (GBM) survival prediction using deep learning (DL) methods. 285 glioma (210 GBM, 75 low-grade glioma) patients were included. 163 of the GBM patients had overall survival (OS) data. Every patient had four pre-operative MR scans and manually drawn tumor contours. For automatic tumor segmentation, a 3D convolutional neural network (CNN) was trained and validated using 122 glioma patients. The trained model was applied to the remaining 163 GBM patients to generate tumor contours. The handcrafted and DL-based radiomic features were extracted from auto-contours using explicitly designed algorithms and a pre-trained CNN respectively. 163 GBM patients were randomly split into training (n=122) and testing (n=41) sets for survival analysis. Cox regression models with regularization techniques were trained to construct the handcrafted and DL-based signatures. The prognostic power of the two signatures was evaluated and compared. The 3D CNN achieved an average Dice coefficient of 0.85 across 163 GBM patients for tumor segmentation. The handcrafted signature achieved a C-index of 0.64 (95% CI: 0.55-0.73), while the DL-based signature achieved a C-index of 0.67 (95% CI: 0.57-0.77). Unlike the handcrafted signature, the DL-based signature successfully stratified testing patients into two prognostically distinct groups (p-value<0.01, HR=2.80, 95% CI: 1.26-6.24). The proposed 3D CNN generated accurate GBM tumor contours from four MR images. The DL-based signature resulted in better GBM survival prediction, in terms of higher C-index and significant patient stratification, than the handcrafted signature. The proposed automatic radiomic workflow demonstrated the potential of improving patient stratification and survival prediction in GBM patients

Targeted metabolome and transcriptome analyses reveal changes in gibberellin and related cell wall-acting enzyme-encoding genes during stipe elongation in Flammulina filiformis

Flammulina filiformis, a typical agaric fungus, is a widely cultivated and consumed edible mushroom. Elongation of its stipe (as the main edible part) is closely related to its yield and commercial traits; however, the endogenous hormones during stipe elongation and their regulatory mechanisms are not well understood. Gibberellin (GA) plays an important role in the regulation of plant growth, but little has been reported in macro fungi. In this study, we first treated F. filiformis stipes in the young stage with PBZ (an inhibitor of GA) and found that PBZ significantly inhibited elongation of the stipe. Then, we performed GA-targeted metabolome and transcriptome analyses of the stipe at both the young and elongation stages. A total of 13 types of GAs were detected in F. filiformis; the contents of ten of them, namely, GA3, GA4, GA8, GA14, GA19, GA20, GA24, GA34, GA44, and GA53, were significantly decreased, and the contents of three (GA5, GA9, and GA29) were significantly increased during stipe elongation. Transcriptome analysis showed that the genes in the terpenoid backbone biosynthesis pathway showed varying expression patterns: HMGS, HMGR, GPS, and FPPS were significantly upregulated, while CPS/KS had no significant difference in transcript level during stipe elongation. In total, 37 P450 genes were annotated to be involved in GA biosynthesis; eight of them were upregulated, twelve were downregulated, and the rest were not differentially expressed. In addition, four types of differentially expressed genes involved in stipe elongation were identified, including six signal transduction genes, five cell cycle-controlling genes, twelve cell wall-related enzymes and six transcription factors. The results identified the types and content of GAs and the expression patterns of their synthesis pathways during elongation in F. filiformis and revealed the molecular mechanisms by which GAs may affect the synthesis of cell wall components and the cell cycle of the stipe through the downstream action of cell wall-related enzymes, transcription factors, signal transduction and cell cycle control, thus regulating stipe elongation. This study is helpful for understanding the roles of GAs in stipe development in mushrooms and lays the foundation for the rational regulation of stipe length in agaric mushrooms during production

Albumin Binding Function: The Potential Earliest Indicator for Liver Function Damage

Background. Currently there is no indicator that can evaluate actual liver lesion for early stages of viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and cirrhosis. Aim of this study was to investigate if albumin binding function could better reflect liver function in these liver diseases. Methods. An observational study was performed on 193 patients with early NAFLD, viral hepatitis, and cirrhosis. Cirrhosis patients were separated according to Child-Pugh score into A, B, and C subgroup. Albumin metal ion binding capacity (Ischemia-modified albumin transformed, IMAT) and fatty acid binding capacity (total binding sites, TBS) were detected. Results. Both IMAT and TBS were significantly decreased in patients with NAFLD and early hepatitis. In hepatitis group, they declined prior to changes of liver enzymes. IMAT was significantly higher in cirrhosis Child-Pugh class A group than hepatitis patients and decreased in Child-Pugh class B and class C patients. Both IMAT/albumin and TBS/albumin decreased significantly in hepatitis and NAFLD group patients. Conclusions. This is the first study to discover changes of albumin metal ion and fatty acid binding capacities prior to conventional biomarkers for liver damage in early stage of liver diseases. They may become potential earliest sensitive indicators for liver function evaluation

Antioxidant effect of yeast on lipid oxidation in salami sausage

Salami is a kind of fermented meat product with rich nutrition and unique flavor. Because it is rich in fat, it is easy to oxidize to produce bad flavor. Compared with the way of adding artificial or natural antioxidants to reduce the degree of sausage oxidation, the antioxidant characteristics of developing the starter itself deserve more attention. In this study, firstly the antioxidant activities of 5 strains of yeast were measured in vitro, and then the mixture of yeast and Lactobacillus rhamnosus YL-1 was applied to fermented sausage model. The effect of the starter in the sausage model was investigated through physicochemical parameters, degree of fat oxidation, free fatty acid content, and though volatile flavor compound analysis, sensory evaluation and various indexes after storage were observed. Metagenomics was used to explore metabolic pathways, functional genes and key enzymes related to lipid oxidizing substances in sausage in yeast. The results showed that Wickerhamomyces anomalus Y12-3 and Y12-4 had strong tolerance to H2O2, and had higher SOD and CAT enzyme activities. The addition of yeast effectively reduced the material value of peroxidation value and active thiobarbiturate in salami. In flavor analysis, the content of flavor compounds associated with lipid oxidation, such as hexanal, heptanal, nonanal and (E)-2-decenal were significantly lower with the use of Debaryomyces hansenii Y4-1 and Y12-3. Meanwhile, the possible pathways of yeast metabolism of flavor substances related to lipid oxidation (mainly aldehydes) were discussed with the help of metagenomic techniques. According to the results of metagenomics, fatty acid degradation (ko00071) metabolic pathway was related to the degradation of aldehydes through aldehyde dehydrogenase, which was the potential key enzyme

Evaluation of current algorithms for segmentation of scar tissue from late Gadolinium enhancement cardiovascular magnetic resonance of the left atrium: an open-access grand challenge

Background: Late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can be used to visualise regions of fibrosis and scarring in the left atrium (LA) myocardium. This can be important for treatment stratification of patients with atrial fibrillation (AF) and for assessment of treatment after radio frequency catheter ablation (RFCA). In this paper we present a standardised evaluation benchmarking framework for algorithms segmenting fibrosis and scar from LGE CMR images. The algorithms reported are the response to an open challenge that was put to the medical imaging community through an ISBI (IEEE International Symposium on Biomedical Imaging) workshop. Methods: The image database consisted of 60 multicenter, multivendor LGE CMR image datasets from patients with AF, with 30 images taken before and 30 after RFCA for the treatment of AF. A reference standard for scar and fibrosis was established by merging manual segmentations from three observers. Furthermore, scar was also quantified using 2, 3 and 4 standard deviations (SD) and full-width-at-half-maximum (FWHM) methods. Seven institutions responded to the challenge: Imperial College (IC), Mevis Fraunhofer (MV), Sunnybrook Health Sciences (SY), Harvard/Boston University (HB), Yale School of Medicine (YL), King’s College London (KCL) and Utah CARMA (UTA, UTB). There were 8 different algorithms evaluated in this study. Results: Some algorithms were able to perform significantly better than SD and FWHM methods in both pre- and post-ablation imaging. Segmentation in pre-ablation images was challenging and good correlation with the reference standard was found in post-ablation images. Overlap scores (out of 100) with the reference standard were as follows: Pre: IC = 37, MV = 22, SY = 17, YL = 48, KCL = 30, UTA = 42, UTB = 45; Post: IC = 76, MV = 85, SY = 73, HB = 76, YL = 84, KCL = 78, UTA = 78, UTB = 72. Conclusions: The study concludes that currently no algorithm is deemed clearly better than others. There is scope for further algorithmic developments in LA fibrosis and scar quantification from LGE CMR images. Benchmarking of future scar segmentation algorithms is thus important. The proposed benchmarking framework is made available as open-source and new participants can evaluate their algorithms via a web-based interface

An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia

Von Willebrand factor-binding protein (vWbp), secreted by Staphylococcus aureus (S. aureus), can activate host prothrombin, convert fibrinogen to fibrin clots, induce blood clotting, and contribute to pathophysiology of S. aureus-related diseases, including infective endocarditis, staphylococcal sepsis and pneumonia. Therefore, vWbp is an promising drug target in the treatment of S. aureus-related infections. Here, we report that dryocrassin ABBA (ABBA), a natural compound derived from Dryopteris crassirhizoma, can significantly inhibit the coagulase activity of vWbp in vitro by directly interacting with vWbp without killing the bacteria or inhibiting the expression of the vWbp. Using molecular dynamics simulations, we demonstrate that ABBA binds to the “central cavity” in the elbow of vWbp by interacting with Arg-70, His-71, Ala-72, Gly-73, Tyr-74, Glu-75, Tyr-83, and Gln-87 in vWbp, thus interfering with the binding of vWbp to prothrombin. Furthermore, in vivo studies demonstrated that ABBA can attenuate injury and inflammation of mouse lung tissues caused by S. aureus and increase survival of mice. Together these findings indicate that ABBA is a promising lead drug for the treatment of S. aureus-related infections. This is the first report of potential inhibitor which inhibit the coagulase activity of vWbp by directly interacting with vWbp

The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair

p400 unwinds chromatin from nucleosomes flanking double-strand breaks to facilitate recruitment of the DNA repair components brca1 and 53BP1

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Activation of Hif1α by the Prolylhydroxylase Inhibitor Dimethyoxalyglycine Decreases Radiosensitivity

Hypoxia inducible factor 1α (Hif1α) is a stress responsive transcription factor, which regulates the expression of genes required for adaption to hypoxia. Hif1α is normally hydroxylated by an oxygen-dependent prolylhydroxylase, leading to degradation and clearance of Hif1α from the cell. Under hypoxic conditions, the activity of the prolylhydroxylase is reduced and Hif1α accumulates. Hif1α is also constitutively expressed in tumor cells, where it is associated with resistance to ionizing radiation. Activation of the Hif1α transcriptional regulatory pathway may therefore function to protect normal cells from DNA damage caused by ionizing radiation. Here, we utilized the prolylhydroxylase inhibitor dimethyloxalylglycine (DMOG) to elevate Hif1α levels in mouse embryonic fibroblasts (MEFs) to determine if DMOG could function as a radioprotector. The results demonstrate that DMOG increased Hif1α protein levels and decreased the sensitivity of MEFs to ionizing radiation. Further, the ability of DMOG to function as a radioprotector required Hif1α, indicating a key role for Hif1α's transcriptional activity. DMOG also induced the Hif1α -dependent accumulation of several DNA damage response proteins, including CHD4 and MTA3 (sub-units of the NuRD deacetylase complex) and the Suv39h1 histone H3 methyltransferase. Depletion of Suv39h1, but not CHD4 or MTA3, reduced the ability of DMOG to protect cells from radiation damage, implicating increased histone H3 methylation in the radioprotection of cells. Finally, treatment of mice with DMOG prior to total body irradiation resulted in significant radioprotection of the mice, demonstrating the utility of DMOG and related prolylhydroxylase inhibitors to protect whole organisms from ionizing radiation. Activation of Hif1α through prolylhydroxylase inhibition therefore identifies a new pathway for the development of novel radiation protectors