Systems Genomics of Thigh Adipose Tissue From Asian Indian Type-2 Diabetics Revealed Distinct Protein Interaction Hubs

We performed a systematic analysis of genes implicated in thigh subcutaneous adipose tissue of Asian Indian Type 2 Diabetes Mellitus (AIT2DM) and created a phenome-interactome network. This analysis was performed on 60 subjects specific to limb thigh fat by integrating phenotypic traits and similarity scores associated with AIT2DM. Using a phenotypic attribute, a contextual neighbor was identified across all the traits, viz. body mass index (BMI) statistics, adipocyte size, lipid parameters, homeostatic model assessment- insulin resistance (HOMA-IR), HOMA-ß. In this work, we have attempted to characterize transcription signatures using the phenome-interactome maps where each of the traits under study including the intermediary phenotypes has a distinct set of genes forming the hubs. Furthermore, we have identified various clinical, biochemical, and radiological parameters which show significant correlation with distinct hubs. We observed a number of novel pathways and genes including those that are non-coding RNAs implicated in AIT2DM.We showed that they appear to be associated with pathways, viz. tyrosine kinase JAK2, NOTCH thereby recruiting signaling molecules such as STAT5 and Src family kinases on the cell surface regulated them and our analyses comprising significant hubs suggest that thigh subcutaneous adipose tissue plays a role in pathophysiology of AIT2DM

Highly sensitive stripping voltammetric determination of a biomolecule, pyruvic acid in solubilized system and biological fluids

AbstractElectroreduction and adsorption behavior of pyruvic acid were studied in the presence of cetyltrimethylammonium bromide by using cyclic voltammetry, differential pulse adsorptive stripping voltammetry and square-wave adsorptive stripping voltammetry at HMDE. The reduction peak current increases in the presence of CTAB. These fully validated sensitive and reproducible adsorptive stripping voltammetric techniques were applied for the trace determination of the pyruvic acid in biological samples. Pyruvic acid shows a single irreversible reduction peak at −1.35V in ammonia buffer of pH 8.2±0.01. Different experimental conditions were examined by using differential pulse adsorptive stripping voltammetry and square wave adsorptive stripping voltammetry. These electroanalytical procedures enabled to determine pyruvic acid in the concentration range 0.004–0.036mM for both DPAdSV and SWAdSV. The detection and quantification limits were found to be 6.12×10−6 and 2.0×10−5mM for DPAdSV and 1.12×10−7 and 4.4×10−6mM for SWAdSV, respectively

Analyzing MRI scans to detect glioblastoma tumor using hybrid deep belief networks

Abstract Glioblastoma (GBM) is a stage 4 malignant tumor in which a large portion of tumor cells are reproducing and dividing at any moment. These tumors are life threatening and may result in partial or complete mental and physical disability. In this study, we have proposed a classification model using hybrid deep belief networks (DBN) to classify magnetic resonance imaging (MRI) for GBM tumor. DBN is composed of stacked restricted Boltzmann machines (RBM). DBN often requires a large number of hidden layers that consists of large number of neurons to learn the best features from the raw image data. Hence, computational and space complexity is high and requires a lot of training time. The proposed approach combines DTW with DBN to improve the efficiency of existing DBN model. The results are validated using several statistical parameters. Statistical validation verifies that the combination of DTW and DBN outperformed the other classifiers in terms of training time, space complexity and classification accuracy

A Molecular Docking and Pharmacokinetic Prediction of Thiazolidine-2, 4-dione Derivatives: Toward Novel Therapeutic Targets for Type-2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a leading endocrine disorder that affects millions of people worldwide. It is characterized by hyperglycemia and high insulin resistance. The commonly prescribed oral therapeutic for insulin resistance in T2DM is Thiazolidine-2, 4-diones (TZDs). TZDs are a class of oral hypoglycemic agents that act on Peroxisome proliferator activating receptor-γ (PPAR-γ) receptors and are mainly expressed in the adipose tissues. In this work, we derive novel classes of TZDs and predict the nature of structural affinity using docking studies against the PPAR-γ.

Brain MRI Image Classification for Cancer Detection Using Deep Wavelet Autoencoder-Based Deep Neural Network

Technology and the rapid growth in the area of brain imaging technologies have forever made for a pivotal role in analyzing and focusing the new views of brain anatomy and functions. The mechanism of image processing has widespread usage in the area of medical science for improving the early detection and treatment phases. Deep neural networks (DNN), till date, have demonstrated wonderful performance in classification and segmentation task. Carrying this idea into consideration, in this paper, a technique for image compression using a deep wavelet autoencoder (DWA), which blends the basic feature reduction property of autoencoder along with the image decomposition property of wavelet transform is proposed. The combination of both has a tremendous effect on sinking the size of the feature set for enduring further classification task by using DNN. A brain image dataset was taken and the proposed DWA-DNN image classifier was considered. The performance criterion for the DWA-DNN classifier was compared with other existing classifiers such as autoencoder-DNN or DNN, and it was noted that the proposed method outshines the existing methods

Daksha: On Alert for High Energy Transients

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper.Comment: 9 pages, 3 figures, 1 table. Additional information about the mission is available at https://www.dakshasat.in

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention