Structural, material and antibacterial properties of quercetin incorporated soy protein isolate films and its binding behavior through molecular docking.

This study aimed to investigate the three different methods for the fabrication of quercetin (1%-3% w/w of protein) incorporated soy protein isolate (SPI) films and their effect on material properties. The quercetin incorporated SPI films prepared by these methods were characterized by Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectrophotometer, tensile properties, and water uptake and leaching properties. The cross-linking pattern was revealed by the FTIR spectrum that showed formation of an ester group because of interaction between the quercetin hydroxyl group and the carboxyl side chain of SPI amino acids. The tensile strength of SPI films were enhanced with the addition of quercetin as it increased to a maximum of 6.17 MPa while neat SPI film had tensile strength 4.13 MPa. The prepared films exhibit significant antibacterial activity against Listeria monocytogenes and Escherichia coli. The In-silico docking analysis demonstrates that covalent and non-covalent forces play crucial roles in binding interaction. It shows the formation of four hydrogen bonds, two salt bridges along with one pi-alkyl interaction. The simulation studies reflect the crucial amino acid residues involved in SPI-quercetin binding. The effect of quercetin binding with SPI on its stability and compactness is revealed by Root mean square deviation (RMSD) and radius of gyration studies.

In-silico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel antiapoptotic protein of Porphyromonas gingivalis.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

In vitro and in vivo removal efficacy of insoluble Prussian blue in combination with calcium polystyrene sulfonate for thallium.

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg-1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg-1, orally, twice a day, PB 3 g kg-1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g-1) as compared to PB (37.771 mg g-1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.

Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against fimbriae (FimA) protein of Porphyromonas gingivalis in oral squamous cell carcinoma.

Oral cancer is among the most common cancer in the world. Tobacco, alcohol, and viruses have been regarded as a well- known risk factors of OCC however, 15% of OSCC cases occurred each year without these known risk factors. Recently a myriad of studies has shown that bacterial infections lead to cancer. Accumulated shreds of evidence have demonstrated the role of Porphyromonas gingivalis (P. gingivalis) in OSCC. The virulence factor FimA of P. gingivalis activates the oncogenic pathways in OSCC by upregulating various cytokines. It also led to the inactivation of a tumor suppressor protein p53. The present Insilico study uses High-Throughput Virtual Screening, molecular docking, and molecular dynamics techniques to find the potential compounds against the target protein FimA. The goal of this study is to identify the anti-cancer lead compounds retrieved from natural sources that can be used to develop potent drug molecules to treat P.gingivalis-related OSCC. The anticancer natural compounds library was screened to identify the potential lead compounds. Furthermore, these lead compounds were subjected to precise docking, and based on the docking score potential lead compounds were identified. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this insilico finding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC. Workflow of Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against Fimbriae (FimA) protein of P. gingivalis in oral squamous cell carcinoma.

Identification of phytochemical inhibitors targeting phosphate acetyltransferase of Mycoplasma genitalium: insights from virtual screening and molecular dynamics studies.

Mycoplasma genitalium (M. genitalium) has evolved as a superbug, and the developing antimicrobial resistance with just a few treatment options available is an imminent concern. Due to the emergence of antibiotic resistance, a new antibiotic class or medications are required to combat this pathogen. The phosphate acetyltransferase (PTA) enzyme can be a suitable drug target which is essential for M. genitalium survival and involves in acetate metabolism. To efficiently find potent inhibitors, structure-based drug design approaches targeting the PTA of M. genitalium have been established. In this study, the three most potent phytochemical inhibitors were predicted from virtual screening and these are sitostanyl ferulate, beta-sitosterol-beta-D-glucoside, and brassinolide, with binding energies of - 9.66, - 9.60, and - 9.48 kcal/mol, respectively. The active site residues Thr-125, Arg-300, Ser-299, Tyr-272, and Lys-273 appear to be critical in binding the three predicted potent inhibitors. The results of the molecular dynamics study indicate that the three predicted phytochemical inhibitors have formed stable bonds with PTA. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) was utilized for the estimation of binding free energy of PTA-phytochemical complexes. Taken together, the findings of our computational work might aid in the development of possible potential drugs to treat and ameliorate the severity of M. genitalium infection.

Energy-Efficient and Variability-Resilient 11T SRAM Design Using Data-Aware Read-Write Assist (DARWA) Technique for Low-Power Applications.

The need for power-efficient devices, such as smart sensor nodes, mobile devices, and portable digital gadgets, is markedly increasing and these devices are becoming commonly used in daily life. These devices continue to demand an energy-efficient cache memory designed on Static Random-Access Memory (SRAM) with enhanced speed, performance, and stability to perform on-chip data processing and faster computations. This paper presents an energy-efficient and variability-resilient 11T (E2VR11T) SRAM cell, which is designed with a novel Data-Aware Read-Write Assist (DARWA) technique. The E2VR11T cell comprises 11 transistors and operates with single-ended read and dynamic differential write circuits. The simulated results in a 45 nm CMOS technology exhibit 71.63% and 58.77% lower read energy than ST9T and LP10T and lower write energies of 28.25% and 51.79% against S8T and LP10T cells, respectively. The leakage power is reduced by 56.32% and 40.90% compared to ST9T and LP10T cells. The read static noise margin (RSNM) is improved by 1.94× and 0.18×, while the write noise margin (WNM) is improved by 19.57% and 8.70% against C6T and S8T cells. The variability investigation using the Monte Carlo simulation on 5000 samples highly validates the robustness and variability resilience of the proposed cell. The improved overall performance of the proposed E2VR11T cell makes it suitable for low-power applications.

Modulation of GmFAD3 expression alters abiotic stress responses in soybean.

KEY MESSAGE: This study focused on enhancing resilience of soybean crops to drought and salinity stresses by overexpression of GmFAD3A gene, which plays an important role in modulating membrane fluidity and ultimately influence plants response to various abiotic stresses. Fatty acid desaturases (FADs) are a class of enzymes that mediate desaturation of fatty acids by introducing double bonds. They play an important role in modulating membrane fluidity in response to various abiotic stresses. However, a comprehensive analysis of GmFAD3 in drought and salinity stress tolerance in soybean is lacking. We used bean pod mottle virus (BPMV)-based vector for achieving rapid and efficient overexpression as well as silencing of Omega-3 Fatty Acid Desaturase gene from Glycine max (GmFAD3) to assess the functional role of GmFAD3 in abiotic stress responses in soybean. Higher levels of recombinant BPMV-GmFAD3A transcripts were detected in overexpressing soybean plants. Overexpression of GmFAD3A in soybean resulted in increased levels of jasmonic acid and higher expression of GmWRKY54 as compared to mock-inoculated, vector-infected and FAD3-silenced soybean plants under drought and salinity stress conditions. The GmFAD3A-overexpressing plants showed higher levels of chlorophyll content, efficient photosystem-II, relative water content, transpiration rate, stomatal conductance, proline content and also cooler canopy under drought and salinity stress conditions as compared to mock-inoculated, vector-infected and FAD3-silenced soybean plants. Results from the current study revealed that GmFAD3A-overexpressing soybean plants exhibited tolerance to drought and salinity stresses. However, soybean plants silenced for GmFAD3 were vulnerable to drought and salinity stresses.

The Adaptation and Tolerance of Major Cereals and Legumes to Important Abiotic Stresses.

Abiotic stresses, including drought, extreme temperatures, salinity, and waterlogging, are the major constraints in crop production. These abiotic stresses are likely to be amplified by climate change with varying temporal and spatial dimensions across the globe. The knowledge about the effects of abiotic stressors on major cereal and legume crops is essential for effective management in unfavorable agro-ecologies. These crops are critical components of cropping systems and the daily diets of millions across the globe. Major cereals like rice, wheat, and maize are highly vulnerable to abiotic stresses, while many grain legumes are grown in abiotic stress-prone areas. Despite extensive investigations, abiotic stress tolerance in crop plants is not fully understood. Current insights into the abiotic stress responses of plants have shown the potential to improve crop tolerance to abiotic stresses. Studies aimed at stress tolerance mechanisms have resulted in the elucidation of traits associated with tolerance in plants, in addition to the molecular control of stress-responsive genes. Some of these studies have paved the way for new opportunities to address the molecular basis of stress responses in plants and identify novel traits and associated genes for the genetic improvement of crop plants. The present review examines the responses of crops under abiotic stresses in terms of changes in morphology, physiology, and biochemistry, focusing on major cereals and legume crops. It also explores emerging opportunities to accelerate our efforts to identify desired traits and genes associated with stress tolerance.

Microbiological status of drinking water sources and its relationship with human health in Solan, India.

In Solan district, the developmental activities associated with chemical based farming, rapid urbanization, and rampant industrialization have led to many diarrhoeal, gastroenteritis, and hepatitis disease outbreaks. This has necessitated for microbiological assessment of indicator organisms, the thermotolerant coliforms, in drinking water sources, and their relationship with diarrhoeal disease. All the 49 Public Health Institutes (PHIs) of the district were categorized into very low, low, moderate, and high disease burden regions by stratification method. For drinking water, 55.5, 16.5, and 17% people preferred springs, borewells, and hand-pump respectively. These sources inventoried by Knowledge, Attitude, and Practice survey in one of very low and seven of high disease burden regions, and were analyzed by multiple tube fermentation technique. A cross-sectional survey of 200 children was undertaken for diarrhoeal disease estimation. Parwanoo, an industrial and Kurgal, a non industrial region witnessed highest (30.20) and lowest (4.40) Most Probable Number (MPN) per 100 ml water of thermotolerant coliforms, respectively. Thermotolerant coliforms were also observed significantly more (16.77 MPN/100 ml water) in monsoon than in post monsoon season (9.04 MPN per 100 ml water). The thermotolerant coliform Escherichia coli was recovered from six and three water sources respectively during monsoon and post monsoon. A strong correlation (r = 0.78) existed between the diarrhoeal disease occurrence and the concentration of thermotolerant coliforms in monsoon whereas it was moderate (r = 0.61) in post monsoon. The study indicated more contamination of water sources due to industrial activities which further got aggravated during the rainy season of the region.

Hyperinflammation and Immune Response Generation in COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. The pathophysiology of this virus is not very clearly known, thus, enormous efforts are being made by the scientific community to delineate its evading mechanism. In this review, we have summarized the hyperinflammation and humoral and cell-mediated immune response generated in human body after infection with the SARS-CoV-2 virus. The inflammatory response generated after infection by increased proinflammatory cytokines and chemokines, and complement proteins activation may likely contribute to disease severity. We also discussed the other factors that may affect immunity and could be important comorbidities in the disease severity and outcome.

Whole Genome Re-sequencing of Soybean Accession EC241780 Providing Genomic Landscape of Candidate Genes Involved in Rust Resistance.

BACKGROUND: In this study, whole genome re-sequencing of rust resistant soybean genotype EC241780 was performed to understand the genomic landscape involved in the resistance mechanism. METHODS: A total of 374 million raw reads were obtained with paired-end sequencing performed with Illumina HiSeq 2500 instrument, out of which 287.3 million high quality reads were mapped to Williams 82 reference genome. Comparative sequence analysis of EC241780 with rust susceptible cultivars Williams 82 and JS 335 was performed to identify sequence variation and to prioritise the candidate genes. RESULTS: Comparative analysis indicates that genotype EC241780 has high sequence similarity with rust resistant genotype PI 200492 and the resistance in EC241780 is conferred by the Rpp1 locus. Based on the sequence variations and functional annotations, three genes Glyma18G51715, Glyma18G51741 and Glyma18G51765 encoding for NBS-LRR family protein were identified as the most prominent candidate for Rpp1 locus. CONCLUSION: The study provides insights of genome-wide sequence variation more particularly at Rpp1 loci which will help to develop rust resistant soybean cultivars through efficient exploration of the genomic resource.

Mesenchymal stem cells from orthodontic premolar teeth.

BACKGROUND: Considering the limitations in isolating Bone Marrow Mesenchymal Stem Cells (BMSCs), alternate sources of Mesenchymal Stem Cells (MSCs) are being intensely investigated. This study evaluated dental pulp MSCs (DP-MSCs) isolated from orthodontically extracted premolar teeth from a bone tissue engineering perspective. METHODS: MSCs isolated from premolar teeth pulp were cultured and studied using BMSCs as the control. Flow cytometry analysis was performed for the positive and negative MSC markers. Multilineage differentiation focusing on bone regeneration was evaluated by specific growth induction culturing media and by alkaline phosphatase (ALP) activity. Data were compared by repeated measurement analysis of variance and Student's t-test at a p value <0.05. RESULTS: Proliferation rate, population doubling time, and colony formation of DP-MSCs were significantly higher (p < 0.001) than BMSCs. More than 85% of DP-MSCs expressed CD44, CD73, CD90, CD105, and CD166. Negative reaction was found for CD11b CD33, CD34, and CD45. Positive reaction was displayed by 7.2% of cells for early MSC marker, Stro-1. Both the cell populations differentiated into adipogenic, osteogenic, and chondrogenic lineages, with adequate ALP expression. CONCLUSION: Because DP-MSCs from orthodontic premolars hold a neural crest/ectomesenchymal ancestry, its prudent growth characteristics and multilineage differentiation open up exciting options in craniofacial tissue engineering.

Defining the Role of Physiotherapy in Palliative Care in Multiple Sclerosis.

With increasing prevalence of multiple sclerosis worldwide, India too has transitioned from low to medium prevalence region. This increases the overall burden of a number of people suffering from a chronic progressive disorder. Such scenario underlines the need for an early comprehensive and holistic patient management plan, aiming to provide a better quality of life. The presented case is one such example of a patient-centered, and interdisciplinary team approach for better management of a patient suffering from an incurable, progressive disorder. As physiotherapists tend to spend a considerable amount of time with their patients on a regular basis, it becomes imperative to view all the patient related problems from a wider angle and endeavor to address each of them individually/collaboratively. In a palliative care setting, physiotherapy can no longer be considered as only physical symptom management approach but a patient care approach considering their entire physical, emotional, psychosocial, and spiritual needs. This novel case report shall serve as a guiding strategy for physiotherapists to work in the domain of palliative care.

Genetic changes in influenza A(H3N2) viruses circulating during 2011 to 2013 in northern India (Lucknow).

Genetic variability in the hemagglutinin (HA1) and the neuraminidase (NA) genes of influenza viruses results in the emergence of new strains which differ in pathogenicity and severity. The present study was undertaken for genotypic characterization of the HA1 and NA genes of the influenza A(H3N2) strains, detected during the 2011-2013. A total of fifty five influenza A(H3N2) positive samples [2011 (n = 20), 2012 (n = 4) and 2013 (n = 31)] were studied. The 824 bp segment of HA1 gene and 931 bp segment of NA gene were amplified and sequenced by Big-Dye terminator kit on ABI3130, Genetic analyzer. Molecular and phylogenetic analysis was done by MEGA 5.05 software and PhyML program (v3.0). Mutations were determined by comparing the deduced amino acid sequences of study strains with that of 2009-2013 vaccine strains. The studied influenza A(H3N2) strains showed 98.1-99.6% similarity in HA1 and NA amino acid sequences with the influenza A/Victoria/361/2011 vaccine strain. Four mutations in the HA1 amino acid sequences (T128A, R142G, L157S and N278K) and three unique mutations in the NA amino acid sequences [D251V, S315G and V313A] were found. These mutations were observed only in strains from the year 2013 (cluster II). None of the strains showed the presence of mutations, N294S and R292K, markers of oseltamivir resistance. In conclusion, Lucknow strains have accumulated the significant number of mutations in the antigenic sites of the HA and the NA coding sequences and continue to be evolving from the 2013 vaccine strain [A/Victoria/361/2011], however, mutations specific for oseltamivir resistance were not detected.

Molecular characterization of circulating pandemic strains of influenza A virus during 2012 to 2013 in Lucknow (India).

The pandemic H1N1 strain of Influenza A virus [A(H1N1)pdm09] is now well adapted in human populations. However, it is still causing sporadic outbreaks worldwide with different severity. The present study was planned to understand the genetic diversity (based on the HA1 gene) of influenza A(H1N1)pdm09 strains circulating during the post pandemic period. The HA1 gene was selected because the HA1 protein is immunogenic, functions as a receptor binding site and indirectly affects transmission and pathogenicity of virus. A total of 2,818 cases were enrolled. Nasal/throat swabs from all cases were tested by one-step real time PCR for detection of influenza virus types and subtypes according to the CDC protocol. Of these, 134 cases were A(H1N1)pdm09 positive, 34 of which were screened for HA1 gene (position 434-905) sequencing (Big-Dye terminator using 3130 ABI, Genetic analyzer). Molecular and phylogenetic analysis was performed using PhyML approach (v. 3.0). All A(H1N1)pdm09 positive and negative cases were clinically characterized. Phylogentically, all Lucknow strains (n = 33) except one fall with the clade seven reference strain. One strain showed 99.9% similarities with clade one reference strain A/California/07/2009. In mutational analysis, 33 strains had the S220T mutation, which is at an antigenic site and characteristic of clade seven along with few minor mutations; K180I/T/Q, V190I, S200P, S202T, A203T, A214T, S220T, V251I, and A273T. These results suggest that clade seven was the most widely circulating clade in Lucknow and A(H1N1)pdm09 cases showed mild clinical symptoms as compared to A(H3N2) or influenza B cases.

Influenza virus genotypes circulating in and around Lucknow, Uttar Pradesh, India, during post pandemic period, August 2010--September 2012.

BACKGROUND & OBJECTIVES: During the post influenza pandemic period, continuous surveillance of influenza virus and its subtypes is mandatory to help the policy makers to take effective and appropriate decisions. Therefore, this study was planned to determine the pattern of influenza virus activity in context to various meteorological and clinical parameters in and around Lucknow, Uttar Pradesh, India, during post pandemic period August 2010 - September 2012. METHODS: Nasal swabs/throat swabs/nasopharyngeal aspirates of 2669 patients were collected. One-step real time PCR for detection of influenza virus was done according to the Centers for Disease Control and Prevention (CDC) protocol. RESULTS: Influenza positivity was 15.8 per cent (423/2669) in symptomatic patients. Of the 423 total positives, 192 (7.2%) were influenza A and 231 (8.7%) were influenza B. Positivity for influenza virus was significantly (P=0.001, OR=2.9, CI=1.9-4.3) higher in patients with Influenza like illness (ILI) (17.4%, 396/2271) than those with severe acute respiratory illness (SARI) (6.8%, 27/398). Influenza A positive samples were subtyped as; pdmH1N1 (67.2%, 129/192) and seasonal H3N2 (32.8%, 63/192). It significantly correlated with monthly mean rainfall, humidity and dew point while atmospheric pressure was inversely related. No significant association was found with temperature and wind speed. Clinical variations were observed between different strains of Influenza virus. INTERPRETATION & CONCLUSIONS: The findings provide a clear picture of different clinical presentations of various strains of influenza A and B viruses and epidemiology of influenza infection from Lucknow (UP), India. The seasonality of influenza virus infection showed variation in relation to different environmental factors. Pandemic H1N1 caused more systemic infection than seasonal influenza A/H3N2 virus.

TB LAMP assay, a beneficial tool for the diagnosis of Tubercular meningitis in resource-limited settings.

INTRODUCTION: Tubercular meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological sequelae. The estimated mortality due to TBM in India is 1.5 per 100,000 population. In resource-limited settings, only the Ziehl-Neelsen (ZN) stain, which has very little sensitivity, is available. The World Health Organization recommended the Loop Mediated Isothermal Amplification (TB LAMP) assay for pulmonary tuberculosis only. We evaluated this test for tubercular meningitis as well. METHODOLOGY: In a cross-sectional study of 2-year duration, we have taken 239 cerebrospinal fluid samples from suspected cases of tubercular meningitis patients. ZN staining along with Mycobacteria Growth Indicator Tube (MGIT) TB culture, Xpert MTB/RIF Ultra assay, and commercial TB LAMP assay were performed for each sample. RESULTS: Out of 239 samples, 40 samples (16.73%) were found TB LAMP assay positive, 48 samples (20.08%) were found Xpert ultra-assay positive, 12 samples (5.02%) were MGIT TB culture positive and acid-fast bacillus smear positive in ten samples (4.18 %). Out of 12 MGIT-positive samples, all samples (100%) were TB LAMP and Xpert ultra positive and one sample (8.33%) was ZN smear positive. In 199 negative samples from the TB LAMP assay, eight samples were positive by Xpert, none by MGIT TB culture and AFB smear. Sensitivity and specificity were found as 100% and 87.66%, respectively, for the TB LAMP assay. CONCLUSION: TB LAMP assay is a rapid, cost-effective, sensitive, and specific test for tubercular meningitis infection in resource-limited settings.

Whole genome sequence analysis of shallot virus X from India reveals it to be a natural recombinant with positive selection pressure.

BACKGROUND: Shallots are infected by various viruses like Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), Shallot latent virus (SLV) and Shallot virus X (ShVX). In India, they have been found to be persistently infected by ShVX. ShVX also infects onion and garlic in combination with other carlaviruses and potyviruses. ShVX is a member of genus Allexivirus of family Alphaflexiviridae. ShVX has a monopartite genome, which is represented by positive sense single-stranded RNA. Globally, only six complete and 3 nearly complete genome sequences of ShV X are reported to date. This number is insufficient to measure a taxon's true molecular diversity. Moreover, the complete genome sequence of ShVX from Asia has not been reported as yet. Therefore, this study was undertaken to generate a complete genome sequence of ShVX from India. RESULTS: Shallot virus X (ShVX) is one of the significant threats to Allium crop production. In this study, we report the first complete genome sequence of the ShVX from India through Next-generation sequencing (NGS). The complete genome of the ShVX (Accession No. OK104171), from this study comprised 8911 nucleotides. In-silico analysis of the sequence revealed variability between this isolate and isolates from other countries. The dissimilarities are spread all over the genome specifically some non-coding intergenic regions. Statistical analysis of individual genes for site-specific selection indicates a positive selection in NABP region. The presence of a recombination event was detected in coat protein region. The sequence similarity percentage and phylogenetic analysis indicate ShVX Indian isolate is a distinctly different isolate. Recombination and site-specific selection may have a function in the evolution of this isolate. This is the first detailed study of the ShVX complete genome sequence from Southeast Asia. CONCLUSION: This study presents the first report of the entire genome sequence of an Indian isolate of ShVX along with an in-depth exploration of its evolutionary traits. The findings highlight the Indian variant as a naturally occurring recombinant, emphasizing the substantial role of recombination in the evolution of this viral species. This insight into the molecular diversity of strains within a specific geographical region holds immense significance for comprehending and forecasting potential epidemics. Consequently, the insights garnered from this research hold practical value for shaping ShVX management strategies and providing a foundation for forthcoming studies delving into its evolutionary trajectory.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.