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A comprehensive knowledge on systems biology of severe acute respiratory syndrome coronavirus 2 is crucial for differential diagnosis of COVID-19. Interestingly, the radiological and pathological features of COVID-19 mimic that of hypersensitivity pneumonitis (HP), another pulmonary fibrotic phenotype. This motivated us to explore the overlapping pathophysiology of COVID-19 and HP, if any, and using a systems biology approach. Two datasets were obtained from the Gene Expression Omnibus database (GSE147507 and GSE150910) and common differentially expressed genes (DEGs) for both diseases identified. Fourteen common DEGs, significantly altered in both diseases, were found to be implicated in complement activation and growth factor activity. A total of five microRNAs (hsa-miR-1-3p, hsa-miR-20a-5p, hsa-miR-107, hsa-miR-16-5p, and hsa-miR-34b-5p) and five transcription factors (KLF6, ZBTB7A, ELF1, NFIL3, and ZBT33) exhibited highest interaction with these common genes. Next, C3, CFB, MMP-9, and IL1A were identified as common hub genes for both COVID-19 and HP. Finally, these top-ranked genes (hub genes) were evaluated using random forest classifier to discriminate between the disease and control group (coronavirus disease 2019 [COVID-19] vs. controls, and HP vs. controls). This supervised machine learning approach demonstrated 100% and 87.6% accuracy in differentiating COVID-19 from controls, and HP from controls, respectively. These findings provide new molecular leads that inform COVID-19 and HP diagnostics and therapeutics research and innovation. [ABSTRACT FROM AUTHOR]

A library is an open system which in turn belongs to a subsystem of the education system, whose functions are dependent on the community concerned. The National Library plays a vital role in creating human resources and their development in our country. It is a life-long process in the appreciation of the achievement of humanity in knowledge and culture. It also helps in the replenishment of people's spirit by providing books for relaxation and pleasure, with assistance to the students. It performs a significant task in a developing country like India. The progress of a nation mainly depends on education, which provides to its citizens either through formal or non-formal means. In present study the behavioural pattern like their frequency of visit and dependence on the public library has been discussed with special reference to the National Library of India. The paper also explores the information seeking behaviour such as their purpose of visit, materials accessed during their visit to the National Library. The main objective of this study is to examine the services provided by National Library of India to its esteemed users. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) is a relatively rare neurotoxic disorder. A 56-year-old male underwent elective coronary angiography. A Few hours postprocedure, the patient developed bilateral painless vision loss, headache, vomiting and hypertension and was subsequently diagnosed with PRES. Possible trigger factors could be contrast agent used, or hypertension. Contrast agent–induced PRES in hypertensive patients is benign and reversible, and a high-grade suspicion about this possibility is critical for precise management. Our patient was successfully treated with supportive management and was doing well on follow-up. [ABSTRACT FROM AUTHOR]

The study shows a comparative analysis of five BRICS countries National Libraries. We have classified them on the basis of parameters such as their collection, Web2.0 applicability, virtual reference service, website covering language, visitors service, number of institutional repository, software used (digital library or content management software). The website security feature was also discussed as it plays an important role in securing user data. We have also included the user friendliness of impaired persons so that they can also access the websites with ease. The overall analysis found the total collection and rare collections of these national libraries. Most probably the National library of Brazil, Russia and India are more progressive than the other two countries such as China and South Africa. [ABSTRACT FROM AUTHOR]

The B-cell lymphoma/leukemia 11A protein (encoded by BCL11A gene) is a key regulator of fetal-to-adult hemoglobin switching as seen in post-natal life. Although genetic polymorphisms like SNPs in BCL11A gene are expected to affect fetal hemoglobin (HbF) expression levels, yet their implications are poorly studied. This study utilizes a computational approach to identify the deleterious SNPs which may affect the structure and function of BCL11A protein. The study also generated a 3D structure of native and mutants. The analysis identified two SNPs in BCL11A as highly deleterious: N391K and C414S which are expected to affect structure and stability of the protein. According to conservation analysis, both residues N391 and C414 were identified as highly conserved. Additionally, post-translational modification sites were predicted at both sites. Ligand binding sites were also predicted in N391 and C414. Therefore, N391K and C414S in BCL11A can considered as important candidates to mediate HbF variation. • In silico analysis of the deleterious SNPs in BCL11A. • Computational modelling of BCL11A protein. • N391K and C414S are expected to affect structure and stability of the BCL11A protein. [ABSTRACT FROM AUTHOR]

Therapeutic induction of fetal hemoglobin (HbF) is one of the most promising approaches to ameliorate the severity of hemoglobinopathies like β-thalassemia and sickle cell anemia. Although several pharmacological agents have been investigated for HbF induction in adults, the majority of these are associated with significant side-effects. While drug repurposing is known to open new doors for the use of approved drugs in unexplored clinical conditions, the primary challenge lies in identifying such candidates. In this study, we aimed to identify repurposing candidates for HbF induction using a novel in silico approach utilizing microRNA-pathway-drug relationships. A computational drug repurposing strategy identified several unique candidates for HbF induction; among which Curcumin, Ginsenoside, Valproate, and Vorinostat were found to be most suitable for future trials. This study identified new drug repurposing candidates for HbF induction and demonstrates an easily adaptable methodology that can be used for other pathophysiological conditions. • A computational drug repurposing strategy to induce HbF was developed. • MicroRNA-pathway-drug relations identified multiple candidates for HbF induction. • cGMP-PKG and MAPK pathways emerged as the most enriched pathways. • Curcumin, Ginsenoside, Valproate and Vorinostat were found suitable for HbF induction. [ABSTRACT FROM AUTHOR]

Abstract Diseases and pathological ailments are known to perplex clinicians and researchers with their varied clinical manifestations. Such variations are mostly attributed to the complex interplays between numerous molecular players and their modifiers. This complexity in turn baffles scientists further to tweak multiple players together when attempting to identify definitive therapeutic interventions. In this pursuit, researchers often tend to ignore one of the commonest known genetic variations – single nucleotide polymorphisms (SNPs) in non-coding genetic regions. In this study, we demonstrate how SNPs in critical genes and their miRNA regulators may play a crucial role in varied clinical manifestations using the beta-thalassemia clinical spectrum and fetal hemoglobin levels (HbF) as an illustration. A methodological approach using freely available bioinformatics tools was able to identify SNPs in pre-miRNA regions, pre-miRNA flanking regions and miRNA binding sites which in turn are expected to alter the translation process and thereby the expression of HbF. Highlights • Single nucleotide polymorphisms (SNPs) and clinical heterogeneity of diseases. • SNPs in critical genes and their miRNA regulators may play a crucial role in fetal hemoglobin variation in β-thalassemia. • A bioinformatics-based methodological approach to identify polymorphisms in various pre-miRNA & miRNA binding sites. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are well-known as key regulators of diverse biological pathways. A series of experimental evidences have shown that abnormal miRNA expression profiles are responsible for various pathophysiological conditions by modulating genes in disease associated pathways. In spite of the rapid increase in research data confirming such associations, scientists still do not have access to a consolidated database offering these miRNA-pathway association details for critical diseases. We have developed miRwayDB, a database providing comprehensive information of experimentally validated miRNA-pathway associations in various pathophysiological conditions utilizing data collected from published literature. To the best of our knowledge, it is the first database that provides information about experimentally validated miRNA mediated pathway dysregulation as seen specifically in critical human diseases and hence indicative of a cause-and-effect relationship in most cases. The current version of miRwayDB collects an exhaustive list of miRNA-pathway association entries for 76 critical disease conditions by reviewing 663 published articles. Each database entry contains complete information on the name of the pathophysiological condition, associated miRNA(s), experimental sample type(s), regulation pattern (up/down) of miRNA, pathway association(s), targeted member of dysregulated pathway(s) and a brief description. In addition, miRwayDB provides miRNA, gene and pathway score to evaluate the role of a miRNA regulated pathways in various pathophysiological conditions. The database can also be used for other biomedical approaches such as validation of computational analysis, integrated analysis and prediction of computational model. It also offers a submission page to submit novel data from recently published studies. We believe that miRwayDB will be a useful tool for miRNA research community. Database URL : http://www.mirway.iitkgp.ac.in [ABSTRACT FROM AUTHOR]

The various pathophysiological processes occurring in living systems are known to be orchestrated by delicate interplays and cross-talks between different genes and their regulators. Among the various regulators of genes, there is a class of small non-coding RNA molecules known as microRNAs. Although, the relative simplicity of miRNAs and their ability to modulate cellular processes make them attractive therapeutic candidates, their presence in large numbers make it challenging for experimental researchers to interpret the intricacies of the molecular processes they regulate. Most of the existing bioinformatic tools fail to address these challenges. Here, we present a new web resource 'miRnalyze' that has been specifically designed to directly identify the putative regulation of cell signaling pathways bymiRNAs. The tool integratesmiRNA-target predictions with signaling cascade members by utilizing TargetScanHuman 7.1 miRNA-target prediction tool and the KEGG pathway database, and thus provides researchers with in-depth insights into modulation of signal transduction pathways by miRNAs. miRnalyze is capable of identifying common miRNAs targeting more than one gene in the same signaling pathway--a feature that further increases the probability of modulating the pathway and downstream reactions when using miRNA modulators. Additionally, miRnalyze can sort miRNAs according to the seed-match types and TargetScan Contextþþscore, thus providing a hierarchical list of most valuable miRNAs. Furthermore, in order to provide users with comprehensive information regarding miRNAs, genes and pathways, miRnalyze also links to expression data of miRNAs (miRmine) and genes (TiGER) and proteome abundance (PaxDb) data. To validate the capability of the tool, we have documented the correlation of miRnalyze's prediction with experimental confirmation studies. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a fast-growing, underdiagnosed, epidemic. We hypothesise that obesity-related inflammation compromises adipose tissue functions, preventing efficient fat storage, and thus driving ectopic fat accumulation into the liver., Methods: To identify adipose-based mechanisms and potential serum biomarker candidates (SBCs) for NAFLD, we utilise dual-tissue RNA-sequencing (RNA-seq) data in adipose tissue and liver, paired with histology-based NAFLD diagnosis, from the same individuals in a cohort of obese individuals. We first scan for genes that are differentially expressed (DE) for NAFLD in obese individuals' subcutaneous adipose tissue but not in their liver; encode proteins secreted to serum; and show preferential adipose expression. Then the identified genes are filtered to key adipose-origin NAFLD genes by best subset analysis, knockdown experiments during human preadipocyte differentiation, recombinant protein treatment experiments in human liver HepG2 cells, and genetic analysis., Findings: We discover a set of genes, including 10 SBCs, that may modulate NAFLD pathogenesis by impacting adipose tissue function. Based on best subset analysis, we further follow-up on two SBCs CCDC80 and SOD3 by knockdown in human preadipocytes and subsequent differentiation experiments, which show that they modulate crucial adipogenesis genes, LPL, SREBPF1, and LEP. We also show that treatment of the liver HepG2 cells with the CCDC80 and SOD3 recombinant proteins impacts genes related to steatosis and lipid processing, including PPARA, NFE2L2, and RNF128. Finally, utilizing the adipose NAFLD DE gene cis-regulatory variants associated with serum triglycerides (TGs) in extensive genome-wide association studies (GWASs), we demonstrate a unidirectional effect of serum TGs on NAFLD with Mendelian Randomization (MR) analysis. We also demonstrate that a single SNP regulating one of the SBC genes, rs2845885, produces a significant MR result by itself. This supports the conclusion that genetically regulated adipose expression of the NAFLD DE genes may contribute to NAFLD through changes in serum TG levels., Interpretation: Our results from the dual-tissue transcriptomics screening improve the understanding of obesity-related NAFLD by providing a targeted set of 10 adipose tissue-active genes as new serum biomarker candidates for the currently grossly underdiagnosed fatty liver disease., Funding: The work was supported by NIH grants R01HG010505 and R01DK132775. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The KOBS study (J. P.) was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2019), and the Academy of Finland grant (Contract no. 138006). This study was funded by the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant No. 802825 to M. U. K.). K. H. P. was funded by the Academy of Finland (grant numbers 272376, 266286, 314383, and 335443), the Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (grant numbers NNF10OC1013354, NNF17OC0027232, and NNF20OC0060547), Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, University of Helsinki, and Helsinki University Hospital and Government Research Funds. I. S. was funded by the Instrumentarium Science Foundation. Personal grants to U. T. A. were received from the Matti and Vappu Maukonen Foundation, Ella och Georg Ehrnrooths Stiftelse and the Finnish Foundation for Cardiovascular Research., Competing Interests: Declaration of interests J. N. B. received consulting fees from GLG, and support for attending meetings and/or travel from the American Gastroenterology Association (AGA), at least once during the last 36 months. The other authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)