Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has emerged as a global pandemic worldwide. In this study, we used ARTIC primers–based amplicon sequencing to profile 225 SARS-CoV-2 genomes from India. Phylogenetic analysis of 202 high-quality assemblies identified the presence of all the five reported clades 19A, 19B, 20A, 20B, and 20C in the population. The analyses revealed Europe and Southeast Asia as two major routes for introduction of the disease in India followed by local transmission. Interestingly, the19B clade was found to be more prevalent in our sequenced genomes (17%) compared to other genomes reported so far from India. Haplotype network analysis showed evolution of 19A and 19B clades in parallel from predominantly Gujarat state in India, suggesting it to be one of the major routes of disease transmission in India during the months of March and April, whereas 20B and 20C appeared to evolve from 20A. At the same time, 20A and 20B clades depicted prevalence of four common mutations 241 C > T in 5′ UTR, P4715L, F942F along with D614G in the Spike protein. D614G mutation has been reported to increase virus shedding and infectivity. Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1–S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614. Moreover, we also observed an increased concordance of G614 mutation with the viral load, as evident from decreased Ct value of Spike and the ORF1ab gene.
Despite its recent introduction to our centre, the quality of oncological resection using the robotic surgery is comparable to laparoscopy. Lower impotence and QoL scores in patients after robotic procedure may be explained on the basis of better visualisation and precise tissue handling.
Introduction Some studies advocate a laparoscopic extralevator abdominoperineal excision (l-ELAPE) approach for low rectal cancer. The da Vinci™ robot (r-ELAPE) technique has potential to overcome some limitations of l-ELAPE, such as reduction of the learning curve and more precise tissue handling. It is unknown whether this approach results in improved surgical or quality of life outcomes compared with l-ELAPE. This study aimed to address this issue. Methods Consecutive patients having undergone either robotic or laparoscopic ELAPE for adenocarcinoma were studied. All operations were performed by two surgeons experienced in laparoscopic and recently introduced robotic surgery. Surgical outcomes were determined by postoperative histology and short-term complications. Quality of life was prospectively assessed using the European Organisation for Research and Treatment of Cancer QLC-CR30 and QLC-CR29 questionnaires. Results A total of 22 patients (11 r-ELAPE) with a median follow-up of 13 months (8 months robotic; 22 months laparoscopic) were studied. The groups were similarly matched for age, gender, American Society of Anesthesiologists status, preoperative chemoradiotherapy and tumour height. All had R0 resection. There was no significant difference in short-term surgical outcomes between groups. There was no significant difference in mean global health scores between the two groups (74 ± 14 r-ELAPE vs. 73 ± 10 l-ELAPE). The r-ELAPE group had a lower mean impotence score compared with the I-ELAPE group (55.5 ± 40 vs. 72.2 ± 44), although this was not statistically significant. Conclusions The newly introduced r-ELAPE was non-inferior to l-ELAPE in either patient quality of life or surgical outcomes. Robotic surgery could be particularly beneficial in the technically challenging area of low rectal cancer surgery with a shorter learning curve than laparoscopy.
During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying variants of concern (VOC). Viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host single nucleotide variations (iSNVs). Analysing 1347 samples collected till June 2020, we recorded 16 410 iSNV sites throughout the SARS-CoV-2 genome. We found ∼42% of the iSNV sites to be reported as SNVs by 30 September 2020 in consensus sequences submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1774 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineage-defining variations appeared as iSNVs before getting fixed in the population. Besides, mutations in RdRp as well as RNA-editing by APOBEC and ADAR deaminases seem to contribute to the differential prevalence of iSNVs in hosts. We also observe hyper-variability at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions.
Background: India is the world's third leading country in terms of people living with human deficiency virus (HIV) (2.1 million) with 0.4 million deaths due to HIV-associated tuberculosis (TB). Physical and mental stress degrades the quality of life (QOL) in these patients. Studies have been done in HIV patients but very few on HIV-TB co-infected patients. Our study aims at assessing and comparing the QOL in HIV patients with and without TB. Materials and Methods: It was a cross-sectional study done at Antiretroviral Treatment Center of KMC, Mangalore and District Wenlock Hospital, Mangalore, over 6 months. A sample size was 104. Semi-structured questionnaire to collect clinico-demographic data, World Health Organization QOL (WHOQOL)-HIV BREF to assess the QoL, and Beck's Depression Inventory Scale (Physical health, psychological well-being, social relationship, environmental health, level of independence, and spiritual health) to identify depression were used. The Cronbach's alpha was used to measure the internal consistency for each domain of the WHOQOL-HIV instrument. Results: HIV-TB co-infected patients had a lower mean score in all domains as compare to only HIV patients, suggesting that HIV-TB co-infected patients had a poor QOL ( P < 0.05). Internal consistency of each domain was good (α >0.7). Conclusion: To improve the QOL in HIV patients, it is important to identify the determinants of QOL and work toward its improvement.
Recent advances in sequencing technologies and the discovery of non-coding RNAs (ncRNAs) have provided new insights in the molecular pathogenesis of cancers. Several studies have implicated the role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and recently discovered circular RNAs (circRNAs) in tumorigenesis and metastasis. Unlike linear RNAs, circRNAs are highly stable and closed-loop RNA molecules. It has been established that circRNAs regulate gene expression by controlling the functions of miRNAs and RNA-binding protein (RBP) or by translating into proteins. The circRNA–miRNA–mRNA regulatory axis is associated with human diseases, such as cancers, Alzheimer’s disease, and diabetes. In this study, we explored the interaction among circRNAs, miRNAs, and their target genes in various cancers using state-of-the-art bioinformatics tools. We identified differentially expressed circRNAs, miRNAs, and mRNAs on multiple cancers from publicly available data. Furthermore, we identified many crucial drivers and tumor suppressor genes in the circRNA–miRNA–mRNA regulatory axis in various cancers. Together, this study data provide a deeper understanding of the circRNA–miRNA–mRNA regulatory mechanisms in cancers.
Aurora kinase B (AURKB) plays a pivotal role in the regulation of mitosis and is gaining prominence as a therapeutic target in cancers; however, the role of AURKB in retinoblastoma (RB) has not been studied. The purpose of this study was to determine if AURKB plays a role in RB, how its expression is regulated, and whether it could be specifically targeted. METHODS. The protein expression of AURKB was determined using immunohistochemistry in human RB patient specimens and immunoblotting in cell lines. Pharmacological inhibition and shRNA-mediated knockdown were used to understand the role of AURKB in cell viability, apoptosis, and cell cycle distribution. Cell viability in response to AURKB inhibition was also assessed in enucleated RB specimens. Immunoblotting was employed to determine the protein levels of phospho-histone H3, p53, p21, and MYCN. Chromatin immunoprecipitation-qPCR was performed to verify the binding of MYCN on the promoter region of AURKB. RESULTS. The expression of AURKB was found to be markedly elevated in human RB tissues, and the overexpression significantly correlated with optic nerve and anterior chamber invasion. Targeting AURKB with small-molecule inhibitors and shRNAs resulted in reduced cell survival and increased apoptosis and cell cycle arrest at the G2/M phase. More importantly, primary RB specimens showed decreased cell viability in response to pharmacological AURKB inhibition. Additional studies have demonstrated that the MYCN oncogene regulates the expression of AURKB in RB. CONCLUSIONS. AURKB is overexpressed in RB, and targeting it could serve as a novel therapeutic strategy to restrict tumor cell growth.
COVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5’UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.
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