Male sex hormone as a correlate of endothelial function in middle-aged Indian males: a cross-sectional prospective observational study

Background: Data on relationship between serum testosterone and endothelial dysfunction measured by brachial artery flow-mediated dilatation (BAFMD) in Indian subset are scarce. The present study was envisaged to assess the correlation between serum testosterone and endothelial dysfunction measured by BAFMD.Methods: From October 2013 till September 2014, 92 Indian male patients aged 40-60 years who underwent investigation of flow-mediated dilatation of the brachial artery using ultra sonography were included. The association between serum testosterone and BAFMD percent-measured endothelial dysfunction was examined.Results: Multivariate regression analysis in 92 Indian male patients (mean age 53.12±6.3 years) revealed that low levels of total serum, serum free and serum bioavailable testosterone were significantly associated with BAFMD% and were independent of age, hypertension, diabetes, body mass index (BMI), current smoking and hyperlipidaemia (p<0.001). The total serum, serum free and serum bioavailable testosterone were positively correlated with BAFMD% with Pearson correlation coefficients of r=0.572, r=0.525 and r=0.547, respectively (p<0.001).Conclusions: Low levels of total serum, serum free and serum bioavailable testosterone were significantly associated with BAFMD%-measured endothelial dysfunction, irrespective of cardiovascular risk factors

Patterns of lipid profile abnormalities in hypertensive patients and normotensive subjects: a cross-sectional observational study

Background: It is a well-known fact that hypertension and altered lipid profile or dyslipidaemia are leading risk factors for cardiovascular diseases. The coexistence of these two conditions has remained an interesting matter, among cardiologists and researchers alike. In this study, we analysed the serum lipid patterns of hypertensive patients and normotensive control subjects.Methods: This cross-sectional observational study was conducted in a tertiary healthcare and teaching center of Northwestern India during the period of 2010 and 2011. The study comprised of 100 hypertensive patients and 100 normotensive control subjects. Data were collected regarding demographic details, past medical/drug history and lipid profile including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL).Results: A total of 200 subjects with the age above 20 years were enrolled in the study. The mean BMI in hypertensive patients (24.14±2.15 kg/m2) was significantly higher than normotensive subjects (22.60±2.62 kg/m2) (p<0.05). When we compared the mean of TC and TG among the hypertensive patients and normotensive subjects, highly significant differences were obtained (p<0.001). The significant decline in mean HDL level was observed in hypertensive patients than normotensive subjects (40.41±4.57 versus 44.64±5.97, p<0.005).Conclusions: The dyslipidaemia has been more evident among hypertensive patients. Hence, the measurement of blood pressure and lipid profile are of great importance to prevent cardiovascular diseases, stroke and other comorbidities

REINFORCEMENT LEARNING BASED RECOMMENDATION SYSTEM FOR SOFTWARE UPGRADES

A software recommendation system that uses Reinforcement Learning to recommend the most suitable upgradable software versions to a customer. The software recommendation system takes into consideration the user\u27s feedback and applies that learning to unseen cases, resulting in a better customer experience

SARS-CoV-2 contributes to altering the post-transcriptional regulatory networks across human tissues by sponging RNA binding proteins and micro-RNAs

The outbreak of a novel coronavirus SARS-CoV2 responsible for COVID-19 pandemic has caused worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2 mediated alteration on post-transcriptional gene regulation across human tissues remains elusive. In this study, we systematically dissected the crosstalk and dysregulation of human post-transcriptional regulatory networks governed by RNA binding proteins (RBPs) and micro-RNAs (miRs), due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV- 2 encoded proteins directly interact with 51 human RBPs of which majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed functional analysis of differentially expressed genes in mock treated versus SARS-CoV-2 infected lung cells that revealed an enrichment for immune response, cytokine mediated signaling, and metabolism associated genes. This study also characterized the alternative splicing events in SARS-CoV-2 infected cells compared to control demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to viral infection. Motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed an enrichment for RBPs such as SRSFs, PCBPs, ELAVs and HNRNPs illustrating the sponging of RBPs by SARS-CoV-2 genome. Similar analysis to study the interactions of miRs with SARS-CoV-2 revealed the potential for several miRs to be sponged, suggesting that these interactions may contribute to altered pos-transcriptional regulation across human tissues. Given the need to understand the interactions of SARS-CoV-2 with key pos-transcriptional regulators in the human genome, this study provides a systematic analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs, across tissues types during SARS-CoV2 infection.This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM123314 (SCJ). We also thank the lab members for their valuable suggestions and supporting dataset required for completion of this project

An Investigation into Properties of Jackknifed and Bootstrapped Liu-type Estimator

In 2003, Liu proposed a new estimator dealing with the problem of multicollinearity in linear regression model pointing out a drawback of ridge estimator used in this context. This new estimator, called Liu-type estimator was demonstrated to have lesser mean squared error than ridge estimator and ordinary least squares estimator, however, it may carry a large amount of bias. In the present paper, we propose different estimators in order to reduce the bias of Liu-type estimator, one using the Jackknife technique and other using the technique proposed in Kadiyala \cite{kad1984}. We also investigate the Bootstrap method of bias correction on the Liu-type estimator as well. The bias and mean squared error of these estimators have been compared using a simulation study as well as a numerical example. LSTA-2016-005

Transcriptome-wide high-throughput mapping of protein–RNA occupancy profiles using POP-seq

Interaction between proteins and RNA is critical for post-transcriptional regulatory processes. Existing high throughput methods based on crosslinking of the protein–RNA complexes and poly-A pull down are reported to contribute to biases and are not readily amenable for identifying interaction sites on non poly-A RNAs. We present Protein Occupancy Profile-Sequencing (POP-seq), a phase separation based method in three versions, one of which does not require crosslinking, thus providing unbiased protein occupancy profiles on whole cell transcriptome without the requirement of poly-A pulldown. Our study demonstrates that ~ 68% of the total POP-seq peaks exhibited an overlap with publicly available protein–RNA interaction profiles of 97 RNA binding proteins (RBPs) in K562 cells. We show that POP-seq variants consistently capture protein–RNA interaction sites across a broad range of genes including on transcripts encoding for transcription factors (TFs), RNA-Binding Proteins (RBPs) and long non-coding RNAs (lncRNAs). POP-seq identified peaks exhibited a significant enrichment (p value < 2.2e−16) for GWAS SNPs, phenotypic, clinically relevant germline as well as somatic variants reported in cancer genomes, suggesting the prevalence of uncharacterized genomic variation in protein occupied sites on RNA. We demonstrate that the abundance of POP-seq peaks increases with an increase in expression of lncRNAs, suggesting that highly expressed lncRNA are likely to act as sponges for RBPs, contributing to the rewiring of protein–RNA interaction network in cancer cells. Overall, our data supports POP-seq as a robust and cost-effective method that could be applied to primary tissues for mapping global protein occupancies

Jackknifing the Ridge Regression Estimator: A Revisit.

Singh et al. (1986) proposed an almost unbiased ridge estimator using Jackknife method that required transformation of the regression parameters. This article shows that the same method can be used to derive the Jackknifed ridge estimator of the original (untransformed) parameter without transformation. This method also leads in deriving easily the second order Jackknifed ridge that may reduce the bias further. We further investigate the performance of these estimators along with a recent method by Batah et al. (2008) called modified Jackknifed ridge theoretically as well as numerically

Primary pelvic hydatid cyst in a postmenopausal female: a surgical challenge

Primary pelvic hydatid cysts are a rare entity and are often overlooked as a differential diagnosis of a pelvic-space-occupying lesion particularly in non-endemic regions. Unpreparedness and a hasty decision on the surgical approach may end in life-threatening complications and systemic dissemination of the disease. We report the case of a 55-year-old postmenopausal woman with a history of two previous unsuccessful surgeries to remove pelvic cystic lesions due to dense adhesions between the surrounding gut wall, bladder, and the cyst wall. Clinical and imaging findings failed to diagnose the nature of the cysts, and a laparotomy was contemplated. On the third surgical attempt, the clinical suspicion was considered and by meticulous dissection the cysts were removed thoroughly without undue complications. In the postoperative follow-up period there was no sign of disease recurrence or disseminatio