A deep convolutional neural network for segmentation of whole-slide pathology images identifies novel tumour cell-perivascular niche interactions that are associated with poor survival in glioblastoma.

BACKGROUND: Glioblastoma is the most aggressive type of brain cancer with high-levels of intra- and inter-tumour heterogeneity that contribute to its rapid growth and invasion within the brain. However, a spatial characterisation of gene signatures and the cell types expressing these in different tumour locations is still lacking. METHODS: We have used a deep convolutional neural network (DCNN) as a semantic segmentation model to segment seven different tumour regions including leading edge (LE), infiltrating tumour (IT), cellular tumour (CT), cellular tumour microvascular proliferation (CTmvp), cellular tumour pseudopalisading region around necrosis (CTpan), cellular tumour perinecrotic zones (CTpnz) and cellular tumour necrosis (CTne) in digitised glioblastoma histopathological slides from The Cancer Genome Atlas (TCGA). Correlation analysis between segmentation results from tumour images together with matched RNA expression data was performed to identify genetic signatures that are specific to different tumour regions. RESULTS: We found that spatially resolved gene signatures were strongly correlated with survival in patients with defined genetic mutations. Further in silico cell ontology analysis along with single-cell RNA sequencing data from resected glioblastoma tissue samples showed that these tumour regions had different gene signatures, whose expression was driven by different cell types in the regional tumour microenvironment. Our results further pointed to a key role for interactions between microglia/pericytes/monocytes and tumour cells that occur in the IT and CTmvp regions, which may contribute to poor patient survival. CONCLUSIONS: This work identified key histopathological features that correlate with patient survival and detected spatially associated genetic signatures that contribute to tumour-stroma interactions and which should be investigated as new targets in glioblastoma. The source codes and datasets used are available in GitHub: https://github.com/amin20/GBM_WSSM .

Epileptic Seizures Detection in EEG Signals Using Fusion Handcrafted and Deep Learning Features.

Epilepsy is a brain disorder disease that affects people's quality of life. Electroencephalography (EEG) signals are used to diagnose epileptic seizures. This paper provides a computer-aided diagnosis system (CADS) for the automatic diagnosis of epileptic seizures in EEG signals. The proposed method consists of three steps, including preprocessing, feature extraction, and classification. In order to perform the simulations, the Bonn and Freiburg datasets are used. Firstly, we used a band-pass filter with 0.5-40 Hz cut-off frequency for removal artifacts of the EEG datasets. Tunable-Q Wavelet Transform (TQWT) is used for EEG signal decomposition. In the second step, various linear and nonlinear features are extracted from TQWT sub-bands. In this step, various statistical, frequency, and nonlinear features are extracted from the sub-bands. The nonlinear features used are based on fractal dimensions (FDs) and entropy theories. In the classification step, different approaches based on conventional machine learning (ML) and deep learning (DL) are discussed. In this step, a CNN-RNN-based DL method with the number of layers proposed is applied. The extracted features have been fed to the input of the proposed CNN-RNN model, and satisfactory results have been reported. In the classification step, the K-fold cross-validation with k = 10 is employed to demonstrate the effectiveness of the proposed CNN-RNN classification procedure. The results revealed that the proposed CNN-RNN method for Bonn and Freiburg datasets achieved an accuracy of 99.71% and 99.13%, respectively.

Predicting protein structural classes based on complex networks and recurrence analysis.

Protein sequences are divided into four structural classes. The determination of class is a challenging and beneficial task in the bioinformatics field. Several methods have been proposed to this end, but most utilize too many features and produce unsuitable results. In the present, features are extracted based on the predicted secondary structures. At first, predicted secondary structure sequences are mapped into two time series by the chaos game representation. Then, a recurrence matrix is calculated from each of the time series. The recurrence matrix is identified with the adjacency matrix of a complex network and measures are applied for the characterization of complex networks to these recurrence matrixes. For a given protein sequence, a total of 24 characteristic features can be calculated and these are fed into Fisher's discriminated analysis algorithm for classification. To examine the proposed method, two widely used low similarity benchmark datasets design and test its performance. A comparison with the results of existing methods shows that the current study's approach provides a satisfactory performance for protein structural class prediction.

Anthelmintic Activity of Ethanolic and Aqueous Extracts of Khaya grandifoliola Stem Bark against Heligmosomoides polygyrus: In Vitro and In Silico Approaches.

Background: Parasitic infection remains a serious health trade for humans and livestock. The purpose of this study was to present scientific proof of the anthelmintic properties of Khaya grandifoliola, which the native population uses to cure helminthiasis. Method: Fresh Heligmosomoides polygyrus eggs were isolated from faecal samples of experimentally infected mice. The faecal material was cultured, and L1 and L2 larval stages were recovered after 48 and 120 hours, respectively. Using the worm microtracker, the anthelminthic efficacy of the extracts against H. polygyrus was assessed. Two different extracts (aqueous and ethanol extracts) were prepared. For the ovicidal and larvicidal activities, 100 µL of various concentrations of plant extracts, levamisole and 1.5% dimethyl sulfoxide (DMSO), were introduced into a 96-well microplate titer followed by the addition of 100 µL of embryonated eggs (60 eggs) for the ovicidal activity and 100 µL of L 1 or L 2 larvae (50 larvae) for the larvicidal activity. The movement of the worm was monitored for 24 hours in the worm microtracker at 27°C. The Glide module of the Schrodinger Maestro software was used to perform docking studies. Results: For the aqueous extracts, the highest percentage of inhibition of hatching was 42.77 ± 12% at 7.5 mg/mL. The IC50 values for the ethanol (0.36 mg/mL) extract showed that the ethanol extract had a good inhibitory effect on the ability of parasites to hatch from eggs. The inhibition percentage of L1 larvae motility at 7.5 mg/mL was 98.0 ± 1.66% and 83.33 ± 1.66% for ethanol and aqueous extracts, respectively. The negative controls, distilled water and 1.5% DMSO, had no inhibitory impact on larvae. On L1-larvae, the drug of choice levamisole (positive control) had the highest percentage effect (100.0%). Six compounds had the highest docking score and their interactions with the receptor as well. Grandiamide A interacts most with tyrosine, glycine, phenylalanine, asparagine, and serine, and its benzene ring and oxygens inhibit these receptors. Carbonyl and hydroxyl (OH) groups connect grandiamide D to asparagine, isoleucine, and phenylalanine, respectively. By donating hydrogen to the receptor through OH groups, D-glucopyranose-6-phosphate also forms relatively strong hydrogen bonds with its oxygen-bound phosphorus and the receptor. 1-O-deacetylkhayanolide E interacts most with serine and glutamic acid. The carbamic acid benzyl ester of carbamic acid [(1S)-1-phenyl-2-[(4-methylphenyl) sulfinyl] ethyl] interacts most with the receptor with carbonyl groups and with asparagine and serine. With its abundant hydroxide, D-mannitol acts as a hydrogen donor and acceptor and interacts most strongly with amino acids such as glycine, asparagine, aspartic acid, alanine, and glutamic acid. Conclusions: K. grandifoliola extracts possess anthelminthic properties. However, in vivo studies are still necessary to demonstrate the effectiveness of this plant for the treatment of helminthiasis.

In Vitro Anthelmintic Activities of Khaya anthotheca and Faidherbia albida Extracts Used in Chad by Traditional Healers for the Treatment of Helminthiasis and In Silico Study of Phytoconstituents.

Background: Helminthiasis is endemic in Chad and constitutes a public health problem, particularly among school-age children. The aim of this study was to evaluate the anthelmintic activity of extracts of Khaya anthotheca and Faidherbia albida used in Chad by traditional healers for the treatment of helminthiasis. Methods: The anthelmintic activity was assessed against Heligmosomoides polygyrus and Caenorhabditis elegans larvae using the Worm Microtracker. Embryonated eggs, L1, L2, and L3 larvae of H. polygyrus were obtained after 24 h, 48 h, and 7 days of coproculture and L4 larvae of C. elegans culture using standard procedures. One hundred microliters of extracts at various concentrations, with albendazole and distilled water were, put in contact with 100 µL of H. polygyrus suspension (containing 50 parasites at various developmental stages) in a microplate and incubated for 20 h at 25°C in the Worm Microtracker. The same procedure was adopted for C. elegans, but with 180 µL of OP50. 19 µL of C. elegans suspension (containing 50 larvae) was put in contact with 1 µL of extract at various concentrations and incubated in the Worm Microtracker. Docking studies were carried out using the Schrodinger Maestro software's Glide module. The score function in the software was used to rank and group distinct possible adduct structures generated by molecular docking. Results: The aqueous and ethanolic extracts of F. albida at a concentration of 2.5 mg/mL showed the same activity as albendazole (100 ± 0.00) on hatching. The IC50s of the aqueous extracts of the two plants (IC50: 0.6212 mg/mL and 0.71 mg/mL, respectively) were comparable on egg hatching of H. polygyrus with no significant difference (p ≥ 0.05) with respect to the ethanol extracts (IC50: 0.70 mg/mL and 0.81 mg/mL, respectively). There was no significant difference between the percentage inhibition of extracts and albendazole on the L1 larvae of H. polygyrus (p ≥ 0.05). The aqueous extracts acted more effectively than the ethanol extracts on the L1 larvae of H. polygyrus with an IC50 of 0.5588 and ∼9.858e - 005 mg/ml, respectively, for K. anthotheca and F. albida. The aqueous extracts of K. anthotheca and F. albida on L3 larvae of H. polygyrus had inhibitory percentages of 92.6 ± 0.62 and 91.37 ± 0.8 at 2.5 mg/mL which were lower than albendazole (100 ± 0.00). The aqueous extracts of K. anthotheca and F. albida on C. elegance showed IC50 of 0.2775 µg/mL and 0.5115 µg/mL, respectively, and were more effective than the ethanol extracts. Examining K. anthotheca and F. albida through the interaction with the protein receptor and its results also confirmed our assumption that the compound used has hydroxyl and carbonyl groups as well as aromatic rings and is exposed to phenolic and flavonoid groups in a more specific way, and it shows a better inhibitory effect. Conclusions: This study scientifically validates the use of extracts of the two plants in the traditional treatment of helminthiasis. However, it will be necessary to evaluate the in vivo anthelmintic activity and toxicity. Examining the ADME properties of these compounds also supports the potential of these ligands to be transformed into pharmaceutical forms.

Metabolic profiling of Chimonanthus grammatus via UHPLC-HRMS-MS with computer-assisted structure elucidation and its antimicrobial activity.

Chimonanthus grammatus is used as Hakka traditional herb to treat cold, flu, etc. So far, the phytochemistry and antimicrobial compounds have not been well investigated. In this study, the orbitrap-ion trap MS was used to characterize its metabolites, combined with a computer-assisted structure elucidation method, and the antimicrobial activities were assessed by a broth dilution method against 21 human pathogens, as well as the bioassay-guided purification work to clarify its main antimicrobial compounds. A total of 83 compounds were identified with their fragmentation patterns, including terpenoids, coumarins, flavonoids, organic acids, alkaloids, and others. The plant extracts can strongly inhibit the growth of three Gram-positive and four Gram-negative bacteria, and nine active compounds were bioassay-guided isolated, including homalomenol C, jasmonic acid, isofraxidin, quercitrin, stigmasta-7,22-diene-3ß,5α,6α-triol, quercetin, 4-hydroxy-1,10-secocadin-5-ene-1,10-dione, kaempferol, and E-4-(4,8-dimethylnona-3,7-dienyl)furan-2(5H)-one. Among them, isofraxidin, kaempferol, and quercitrin showed significant activity against planktonic Staphylococcus aureus (IC50 = 13.51, 18.08 and 15.86 µg/ml). Moreover, their antibiofilm activities of S. aureus (BIC50 = 15.43, 17.31, 18.86 µg/ml; BEC50 = 45.86, ≥62.50, and 57.62 µg/ml) are higher than ciprofloxacin. The results demonstrated that the isolated antimicrobial compounds played the key role of this herb in combating microbes and provided benefits for its development and quality control, and the computer-assisted structure elucidation method was a powerful tool for chemical analysis, especially for distinguishing isomers with similar structures, which can be used for other complex samples.

The Application of Deep Convolutional Neural Networks to Brain Cancer Images: A Survey.

In recent years, improved deep learning techniques have been applied to biomedical image processing for the classification and segmentation of different tumors based on magnetic resonance imaging (MRI) and histopathological imaging (H&E) clinical information. Deep Convolutional Neural Networks (DCNNs) architectures include tens to hundreds of processing layers that can extract multiple levels of features in image-based data, which would be otherwise very difficult and time-consuming to be recognized and extracted by experts for classification of tumors into different tumor types, as well as segmentation of tumor images. This article summarizes the latest studies of deep learning techniques applied to three different kinds of brain cancer medical images (histology, magnetic resonance, and computed tomography) and highlights current challenges in the field for the broader applicability of DCNN in personalized brain cancer care by focusing on two main applications of DCNNs: classification and segmentation of brain cancer tumors images.

Process optimisation for green synthesis of zero-valent iron nanoparticles using Mentha piperita.

The potential of Mentha piperita in the iron nanoparticles (FeNPs) production was evaluated for the first time. The influences of the variables such as incubation time, temperature, and volume ratio of the extract to metal ions on the nanoparticle size were investigated using central composite design. The appearance of SPR bands at 284 nm in UV-Vis spectra of the mixtures verified the nanoparticle formation. Incubating the aqueous extract and metal precursor with 1.5 volume ratio at 50°C for 30 min leads to the formation of the smallest nanoparticles with the narrowest size distribution. At the optimal condition, the nanoparticles were found to be within the range of 35-50 nm. Experimental measurements of the average nanoparticle size were fitted well to the polynomial model satisfactory with R2 of 0.9078. Among all model terms, the linear term of temperature, the quadratic terms of temperature, and mixing volume ratio have the significant effects on the nanoparticle average size. FeNPs produced at the optimal condition were characterised by transmission electron microscopy, thermogravimetry analysis (TGA), and Fourier-transform infrared spectroscopy. The observed weight loss in the TGA curve confirms the encapsulation of FeNPs by the biomolecules of the extract which were dissociated by heat.