CLIENT COMPANIES’ PERCEPTION TOWARDS CREDIT RISK OF PRIVATE SECTOR BANKS WITH REFERENCE TO ICICI, HDFC, AXIS BANK, IDBI, AND YES BANK

The banking sector at present is facing many issues; one among them is credit risk. Credit risk is termed as an estimate or forecast of the default of a borrower failing to recover his interest amount or borrowed amount. Currently, the banker or the lender is at risk of recovering the interest amount and principal amount, increasing their recovery costs. The present study makes an attempt to know the awareness of customers towards credit risk of private sector banks. The research objective is to analyze the significant association between client company’s perceptions with a view to credit risk. The study explains the major variation between client company’s perspectives towards Indian private sector. The study explains about the impact of credit risk on banks profitability. The present study helps banks to prevail over the problem of credit risk. The study analysis the objectives of research, hypothesis formulated, research methodology, findings and conclusions are discussed. The secondary sources for the study are through the websites of banks, Journals and client company’s websites. Primary data has been gathered from 285 client companies using convenience random sampling technique from private sector banks.

Structural and functional analysis of somatic coding and UTR indels in breast and lung cancer genomes

Insertions and deletions (Indels) represent one of the major variation types in the human genome and have been implicated in diseases including cancer. To study the features of somatic indels in different cancer genomes, we investigated the indels from two large samples of cancer types: invasive breast carcinoma (BRCA) and lung adenocarcinoma (LUAD). Besides mapping somatic indels in both coding and untranslated regions (UTRs) from the cancer whole exome sequences, we investigated the overlap between these indels and transcription factor binding sites (TFBSs), the key elements for regulation of gene expression that have been found in both coding and non-coding sequences. Compared to the germline indels in healthy genomes, somatic indels contain more coding indels with higher than expected frame-shift (FS) indels in cancer genomes. LUAD has a higher ratio of deletions and higher coding and FS indel rates than BRCA. More importantly, these somatic indels in cancer genomes tend to locate in sequences with important functions, which can affect the core secondary structures of proteins and have a bigger overlap with predicted TFBSs in coding regions than the germline indels. The somatic CDS indels are also enriched in highly conserved nucleotides when compared with germline CDS indels.

Regulatory Procedure of Post Approval Changes and Comparative Requirements of EU and USA Regulatory Regions

Aim: The current research paper describes the “Regulatory procedure of post approval changes and comparative regulatory requirement of EU and USA regulatory regions”. Study Design: The present study is a type of Retrospective analysis of Regulatory requirements and the reviewed data was subjected to systemic review. Understanding of the same led to several observations regarding regulatory requirements of EU and USA regulatory regions. Place and Duration of Study: The present study was carried out at Amneal Pharmaceutical Ltd., Ahmedabad, Gujarat, India from January, 2021 to April, 2021. Methodology: Several guidelines were profoundly reviewed to compare the requirements of post approval changes in EU and USA regulatory regions. Various regulatory review aspects were focused i.e. requirements for manufacturing sites addition/or Transfer, process parameters, container and closures, packaging and labelling of medicinal products. Results: The post approval changes in manufacturing sites of solid or semisolid dosage form considered as a major change for USA while considered as Moderate change for EU. The transfer of manufacturing section is major variation for USA while it is a minor but immediate inform type for EU. Change in manufacturing processes, containers, labelling section of sterile products considered as major variation for both. Semisolid and solid categories are falling under the same type of variation for EU and USA regulatory regions. Conclusion: This work demonstrated that the drug approvals in US, EU are the most demanding globally and the available guidance and procedures for the triggered changes are clear in both countries. Applicant should have scientific rationale to any change pertaining to Approved product ; Since the all change control are falling under the scope of Audit, so Applicant should maintain the all the records online.

A large disordered region confers a wide spanning volume to vertebrate Suppressor of Fused as shown in a trans-species solution study.

Hedgehog (Hh) pathway inhibition by the conserved protein Suppressor of Fused (SuFu) is crucial to vertebrate development. By constrast, SuFu removal has little effect in drosophila. Previous publications showed that the crystal structures of human and drosophila SuFu consist of two ordered domains that are capable of breathing motions upon ligand binding. However, the crystal structure of human SuFu does not give information about 20 N-terminal residues (IDR1) and an eighty-residue-long disordered region (IDR2) in the C-terminus, whose function is important for the pathway repression. These two IDRs are species-dependent. We studied SuFu structure in solution, both with circular dichroism and small angle X-ray scattering, comparing drosophila, zebrafish and human species, to better understand this considerable difference. Our studies show that, in spite of similar crystal structures restricted to ordered domains, drosophila and vertebrate SuFu have very different structures in solution. The IDR2 of vertebrates spans a large area, thus enabling it to reach for partners and be accessible for post-translational modifications. Furthermore, we show that the IDR2 region is highly conserved within phyla but varies in length and sequence, with insects having a shorter disordered region while that of vertebrates is broad and mobile. This major variation may explain the different phenotypes observed upon SuFu removal.

Overuse of diagnostic testing in healthcare: a systematic review

BackgroundOveruse of diagnostic testing substantially contributes to healthcare expenses and potentially exposes patients to unnecessary harm. Our objective was to systematically identify and examine studies that assessed the prevalence of diagnostic testing overuse across healthcare settings to estimate the overall prevalence of low-value diagnostic overtesting.MethodsPubMed, Web of Science and Embase were searched from inception until 18 February 2020 to identify articles published in the English language that examined the prevalence of diagnostic testing overuse using database data. Each of the assessments was categorised as using a patient-indication lens, a patient-population lens or a service lens.Results118 assessments of diagnostic testing overuse, extracted from 35 studies, were included in this study. Most included assessments used a patient-indication lens (n=67, 57%), followed by the service lens (n=27, 23%) and patient-population lens (n=24, 20%). Prevalence estimates of diagnostic testing overuse ranged from 0.09% to 97.5% (median prevalence of assessments using a patient-indication lens: 11.0%, patient-population lens: 2.0% and service lens: 30.7%). The majority of assessments (n=85) reported overuse of diagnostic testing to be below 25%. Overuse of diagnostic imaging tests was most often assessed (n=96). Among the 33 assessments reporting high levels of overuse (≥25%), preoperative testing (n=7) and imaging for uncomplicated low back pain (n=6) were most frequently examined. For assessments of similar diagnostic tests, major variation in the prevalence of overuse was observed. Differences in the definitions of low-value tests used, their operationalisation and assessment methods likely contributed to this observed variation.ConclusionOur findings suggest that substantial overuse of diagnostic testing is present with wide variation in overuse. Preoperative testing and imaging for non-specific low back pain are the most frequently identified low-value diagnostic tests. Uniform definitions and assessments are required in order to obtain a more comprehensive understanding of the magnitude of diagnostic testing overuse.

Manganese oxides synthesized via microwave-assisted hydrothermal method: phase evolution and structure refinement

Manganese oxides were synthesized during 40 min at 140 ºC via Microwave-Assisted Hydrothermal (MAH) method and treated at different temperatures in order to evaluate the phase evolution using structure refinement (Rietveld method). The samples obtained were heat treated at temperatures defined by means of thermal analysis (160 ºC, 480 ºC, 715 ºC, 870 ºC, 920 ºC and 1150 ºC) and analyzed by XRD, XRF, FTIR spectroscopy, Raman scattering and SEM. Structural characterizations allowed to identify five distinct phases: α-MnO2, Mn3O4, Mn5O8, Na2Mn5O10 and Na4Mn9O18 with weight percentages dependent on the heat treatment. The hausmannite structure (average crystallite size ranging from 28.9 nm to 99.1 nm) is present in all samples and go through various oxidation and reduction processes from 160 ºC to 1150 ºC without any major variation in the lattice parameters. The results presented enables a better interpretation of the thermal and structural characteristics of manganese oxides synthesized via MAH.

Genomic retargeting of p53 and CTCF is associated with transcriptional changes during oncogenic HRas-induced transformation

Gene transcription is regulated by distant regulatory elements via combinatorial binding of transcription factors. It is increasingly recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene-induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional changes associated with this process. Using Hi-C data, we observe spatial coupling between differentially expressed genes and their differentially accessible regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as determinants of transcriptional alterations at the early stages of oncogenic HRas-induced transformation in human mammary epithelial cells. Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.

Comparative assessments of indel annotations in healthy and cancer genomes with next-generation sequencing data

Background Insertion and deletion (indel) is one of the major variation types in human genomes. Accurate annotation of indels is of paramount importance in genetic variation analysis and investigation of their roles in human diseases. Previous studies revealed a high number of false positives from existing indel calling methods, which limits downstream analyses of the effects of indels on both healthy and disease genomes. In this study, we evaluated seven commonly used general indel calling programs for germline indels and four somatic indel calling programs through comparative analysis to investigate their common features and differences and to explore ways to improve indel annotation accuracy. Methods In our comparative analysis, we adopted a more stringent evaluation approach by considering both the indel positions and the indel types (insertion or deletion sequences) between the samples and the reference set. In addition, we applied an efficient way to use a benchmark for improved performance comparisons for the general indel calling programs Results We found that germline indels in healthy genomes derived by combining several indel calling tools could help remove a large number of false positive indels from individual programs without compromising the number of true positives. The performance comparisons of somatic indel calling programs are more complicated due to the lack of a reliable and comprehensive benchmark. Nevertheless our results revealed large variations among the programs and among cancer types. Conclusions While more accurate indel calling programs are needed, we found that the performance for germline indel annotations can be improved by combining the results from several programs. In addition, well-designed benchmarks for both germline and somatic indels are key in program development and evaluations.

Variation in Mycobacterium tuberculosis genotype and molecular phenotype influence clinical phenotype of Pulmonary tuberculosis and Tuberculous Meningitis infection in host

In the present study, we investigated tissue specific colonization and virulence characteristics of two different Mycobacterium tuberculosis (MTB) clinical isolates derived from patients with Pulmonary TB (PTB) and Tuberculous Meningitis (TBM). We retrospectively studied a total of 1458 patients diagnosed with TB between 2003 and 2013. Of these, archived sputum and CSF samples were available for 323 TBM and 157 PTB patients. We selected a total of 10 sputum and CSF isolates from each group for further molecular characterization. Methodologies employed included, Gas chromatographic analyses of Fatty Acid Methyl Esters (GC-FAME) followed by MTB genotyping to assess strain diversity. We further assessed the molecular phenotype of each strain through in-vitro cytokine assays & murine MTB model. Our comparative genomics data illustrated two diverse genotypes belonging to H37RV (PTB) and CCDC5079 linkage (TBM), highlighting major variation in membrane protein composition and enzymes that make different mycolic acids. The differential cytokine response by both the strains & GC-FAME analysis further corroborated this variation in membrane composition. This was in agreement with KasIII enzyme, LppA and desaturase related variation in protein. Both MTB strains in mice showed diverse pathogenesis with CCDC5079 infected mice exhibiting higher dissemination to brain compared to the H37RV strain which developed progressive pulmonary disease. These observations suggest that variation in the MTB membrane composition could play an important role in differential colonization of these strains. The study warrants further investigation of membrane proteins with respect to blood brain barrier invasion and pathogenesis.

Commonly Applied Selection Criteria for Lung Cancer Screening May Have Strongly Varying Diagnostic Performance in Different Countries

Lung cancer (LC) screening often focuses heavy smokers as a target for screening group. Heavy smoking can thus be regarded as an LC pre-screening test with sensitivities and specificities being different in various populations due to the differences in smoking histories. We derive here expected sensitivities and specificities of various criteria to preselect individuals for LC screening in 27 European countries with diverse smoking prevalences. Sensitivities of various heavy-smoking-based pre-screening criteria were estimated by combining sex-specific proportions of people meeting these criteria in the target population for screening with associations of heavy smoking with LC risk. Expected specificities were approximated by the proportion of individuals not meeting the heavy smoking definition. Estimated sensitivities and specificities varied widely across countries, with sensitivities being generally higher among men (range: 33–80%) than among women (range: 9–79%), and specificities being generally lower among men (range: 48–90%) than among women (range: 70–99%). Major variation in sensitivities and specificities was also seen across different pre-selection criteria for LC screening within individual countries. Our results may inform the design of LC screening programs in European countries and serve as benchmarks for novel alternative or complementary tests for selecting people at high risk for CT-based LC screening.