Comparison between the effects of Maitland's mobilization versus its combination with vastus medialis oblique neuromuscular stimulation on two scales (NPRS & WOMAC) in knee osteoarthritis patients.

Background & objectives: Osteoarthritis (OA) is the most common form of arthritis that increases with age affecting the population from the middle age to the elderly. The present study was undertaken to find whether neuromuscular stimulation of vastus medialis oblique (VMO) in combination with Maitland's mobilization and exercises was more effective as compared to Maitland's mobilization with exercises alone in patients with knee OA. Methods: Sixty patients with knee OA were purposively selected and randomly distributed to two groups that received an intervention for eight weeks. Group A patients received Maitland's mobilization in combination with exercises and group B patients received the same intervention as group A in combination with neuromuscular stimulation of VMO muscle. After eight weeks, outcome measures, i.e. Numeric Pain Rating Scale (NPRS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) index, were reassessed. Results: Both groups showed significant (P<0.05) within-group improvement in the knee pain levels and stiffness as reflected by NPRS and WOMAC index. Interpretation & conclusions: Patients of both the groups (A and B) were found to be improving significantly in pain and disability, group A patients receiving Maitland's mobilization in combination with exercises were found to get more relief in pain and disability.

Genomic landscape of gallbladder cancer: insights from whole exome sequencing.

BACKGROUND: Gallbladder carcinoma (GBC) is a common gastrointestinal malignancy noted for its aggressive characteristics and poor prognosis, which is mostly caused by delayed detection. However, the scarcity of information regarding somatic mutations in Indian patients with GBC has hampered the development of efficient therapeutic options. In the present study, we attempted to bridge this gap by revealing the mutational profile of GBC. MATERIALS AND METHODS: To evaluate the somatic mutation profile, whole exome sequencing (WES) was performed on 66 matched tumor and blood samples from individuals with GBC. Somatic variant calling was performed using GATK pipeline. Variants were annotated at pathogenic and oncogenic levels, using ANNOVAR, VEP tools and the OncoKB database. Mutational signature analysis, oncogenic pathway analysis and cancer driver genes identification were performed at the functional level by using the maftools package. RESULTS: Our findings focused on the eight most altered genes with pathogenic and oncogenic mutations: TP53, SMAD4, ERBB3, KRAS, ARID1A, PIK3CA, RB1, and AXIN1. Genes with pathogenic single nucleotide variations (SNVs) were enriched in oncogenic signaling pathways, particularly RTK-RAS, WNT, and TP53 pathways. Furthermore, our research related certain mutational signatures, such as cosmic 1, cosmic 6, and cosmic 18, 29, to known characteristics including patient age and tobacco smoking, providing important insights into disease etiology. CONCLUSIONS: Given the scarcity of exome-based sequencing studies focusing on the Indian population, this study represents a significant step forward in providing a framework for additional in-depth mutational analysis. Genes with substantial oncogenic and pathogenic mutations are promising candidates for developing targeted mutation panels, particularly for GBC detection.

Somatic mutational landscape across Indian breast cancer cases by whole exome sequencing.

Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions.

Chronic inflammation in the gallbladder leading to persistent epithelium damage promotes invasive cancer. The study aimed to assess the prognostic value of PDL1 and CA19-9 markers in cancer/inflammatory lesions of the gallbladder. A total of 29 cases (19 cancer and 10 inflammatory) were included. The PDL1 protein concentration level and mRNA expression were assessed in the tissues' lysates by ELISA and real-time PCR, respectively. PDL1 and CA19-9 concentration levels were compared and statistically related with clinico-pathological variables. The PDL1 protein level and its relative mRNA expression were correlated. Kaplan-Meir survival and Cox regression analyses were conducted for predicting prognosis. This study investigated the PDL1 and CA19-9 marker expression in both cancer and inflammatory cases of the gallbladder (p = 0.48 and p = 0.17 respectively). PDL1 protein expression was significantly associated with the hormonal profile of the cases (p = 0.04) at an optimum cut-off value of 13 pg/mL, while the CA19-9 marker expression was correlated with the status of liver metastasis (p = 0.0043) and size of the tumor (p = 0.004). A low PDL1 concentration was found when compared to the CA19-9 level among cancer cases (p = 0.12) and proportional in the inflammatory lesions (p = 0.63). A significant positive correlation was found between the PDL1 protein and its relative mRNA expressions in the inflammatory lesions (p = 0.029) when compared to cancer cases (p = 0.069). Our results showed that a protein-based assay for PDL1 expression would be more sensitive compared to RNA based assays for GBC risk stratifications. Overall survival was predicted with CA19-9 and PDL1 levels (p = 0.0074, p = 0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases.

Comparative transcriptome analysis of Rheum australe, an endangered medicinal herb, growing in its natural habitat and those grown in controlled growth chambers.

Rheum australe is an endangered medicinal herb of high altitude alpine region of Himalayas and is known to possess anti-cancerous properties. Unlike many herbs of the region, R. australe has broad leaves. The species thrives well under the environmental extremes in its niche habitat, therefore an understanding of transcriptome of R. australe to environmental cues was of significance. Since, temperature is one of the major environmental variables in the niche of R. australe, transcriptome was studied in the species growing in natural habitat and those grown in growth chambers maintained at 4 °C and 25 °C to understand genes associated with different temperatures. A total of 39,136 primarily assembled transcripts were obtained from 10,17,74,336 clean read, and 21,303 unigenes could match to public databases. An analysis of transcriptome by fragments per kilobase of transcript per million, followed by validation through qRT-PCR showed 22.4% up- and 22.5% down-regulated common differentially expressed genes in the species growing under natural habitat and at 4 °C as compared to those at 25 °C. These genes largely belonged to signaling pathway, transporters, secondary metabolites, phytohormones, and those associated with cellular protection, suggesting their importance in imparting adaptive advantage to R. australe in its niche.

Plant Regulomics Portal (PRP): a comprehensive integrated regulatory information and analysis portal for plant genomes.

Gene regulation is a highly complex and networked phenomenon where multiple tiers of control determine the cell state in a spatio-temporal manner. Among these, the transcription factors, DNA and histone modifications, and post-transcriptional control by small RNAs like miRNAs serve as major regulators. An understanding of the integrative and spatio-temporal impact of these regulatory factors can provide better insights into the state of a 'cell system'. Yet, there are limited resources available to this effect. Therefore, we hereby report an integrative information portal (Plant Regulomics Portal; PRP) for plants for the first time. The portal has been developed by integrating a huge amount of curated data from published sources, RNA-, methylome- and sRNA/miRNA sequencing, histone modifications and repeats, gene ontology, digital gene expression and characterized pathways. The key features of the portal include a regulatory search engine for fetching numerous analytical outputs and tracks of the abovementioned regulators and also a genome browser for integrated visualization of the search results. It also has numerous analytical features for analyses of transcription factors (TFs) and sRNA/miRNA, spot-specific methylation, gene expression and interactions and details of pathways for any given genomic element. It can also provide information on potential RdDM regulation, while facilitating enrichment analysis, generation of visually rich plots and downloading of data in a selective manner. Visualization of intricate biological networks is an important feature which utilizes the Neo4j Graph database making analysis of relationships and long-range system viewing possible. Till date, PRP hosts 571-GB processed data for four plant species namely Arabidopsis thaliana, Oryza sativa subsp. japonica, Zea mays and Glycine max. Database URL: https://scbb.ihbt.res.in/PRP.

Detecting the Molecular System Signatures of Idiopathic Pulmonary Fibrosis through Integrated Genomic Analysis.

Idiopathic Pulmonary Fibrosis (IPF) is an incurable progressive fibrotic disease of the lungs. We currently lack a systematic understanding of IPF biology and a systems approach may offer new therapeutic insights. Here, for the first time, a large volume of high throughput genomics data has been unified to derive the most common molecular signatures of IPF. A set of 39 differentially expressed genes (DEGs) was found critical to distinguish IPF. Using high confidence evidences and experimental data, system level networks for IPF were reconstructed, involving 737 DEGs found common across at least two independent studies. This all provided one of the most comprehensive molecular system views for IPF underlining the regulatory and molecular consequences associated. 56 pathways crosstalks were identified which included critical pathways with specified directionality. The associated steps gained and lost due to crosstalk during IPF were also identified. A serially connected system of five crucial genes was found, potentially controlled by nine miRNAs and eight transcription factors exclusively in IPF when compared to NSIP and Sarcoidosis. Findings from this study have been implemented into a comprehensive molecular and systems database on IPF to facilitate devising diagnostic and therapeutic solutions for this deadly disease.