Browsing by Author "Kumar, Ashutosh"
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Publication A Bioinformatics Tool for Predicting Future COVID-19 Waves Based on a Retrospective Analysis of the Second Wave in India: Model Development Study(JMIR Publications Inc., 2022) Kumar, Ashutosh; Asghar, Adil; Dwivedi, Prakhar; Kumar, Gopichand; Narayan, Ravi K.; Jha, Rakesh K.; Parashar, Rakesh; Sahni, Chetan; Pandey, Sada N.Background: Since the start of the COVID-19 pandemic, health policymakers globally have been attempting to predict an impending wave of COVID-19. India experienced a devastating second wave of COVID-19 in the late first week of May 2021. We retrospectively analyzed the viral genomic sequences and epidemiological data reflecting the emergence and spread of the second wave of COVID-19 in India to construct a prediction model. Objective: We aimed to develop a bioinformatics tool that can predict an impending COVID-19 wave. Methods: We analyzed the time series distribution of genomic sequence data for SARS-CoV-2 and correlated it with epidemiological data for new cases and deaths for the corresponding period of the second wave. In addition, we analyzed the phylodynamics of circulating SARS-CoV-2 variants in the Indian population during the study period. Results: Our prediction analysis showed that the first signs of the arrival of the second wave could be seen by the end of January 2021, about 2 months before its peak in May 2021. By the end of March 2021, it was distinct. B.1.617 lineage variants powered the wave, most notably B.1.617.2 (Delta variant). Conclusions: Based on the observations of this study, we propose that genomic surveillance of SARS-CoV-2 variants, complemented with epidemiological data, can be a promising tool to predict impending COVID-19 waves. � Ashutosh Kumar, Adil Asghar, Prakhar Dwivedi, Gopichand Kumar, Ravi K Narayan, Rakesh K Jha, Rakesh Parashar, Chetan Sahni, Sada N Pandey.Publication Acute and subacute toxicity study of ethanolic extract of Calotropis procera (Aiton) Dryand flower in Swiss albino mice(Elsevier B.V., 2022) Kumar, Ashutosh; Kumar, Brijesh; Kumar, Rajesh; Kumar, Ajay; Singh, Manish; Tiwari, Vinod; Trigunayat, Anshuman; Paul, Paramita; Singh, PratisthaBackground: Calotropis procera is a large shrub which consists many medicinal properties, used in treatment of snake bite, sinus fistula, rheumatism, mumps, burn injuries, inflammation and jaundice traditionally. All the parts of Calotropis procera were utilized in the treatment of diseases out of which leaves and roots were investigated for its toxicity profile that showed dose dependent toxicity. Toxicity profile of flowers of Calotropis procera was not investigated in the previous studies. The aim of this study was to explore the acute and subacute toxicity of ethanolic extract of Calotropis procera flowers for the safe use of traditional medicine. Method: In acute toxicity, a total of 20 female mice (Swiss albino), weighing between 23 and 32 g were randomly divided into four experimental groups: control, 300, 1000, and 2000 mg/kg groups with 5 mice each, and each received a single dose of extract at 300, 1000, or 2000 mg/kg, respectively. Animals were monitored for 14 days. In the subacute study, a total of 40 mice (23�32 g) were divided into 4 groups, each containing males and females. Group 1 (control group) received vehicle and groups 2, 3, and 4 received extract at doses of 300 mg/Kg, 1000 mg/Kg, 2000 mg/Kg of b.w., respectively, for 28 consecutive days. The study was conducted in compliance with the OECD guidelines 407 and 423. Results: Acute toxicity study showed no mortality at the dose of 2000 mg/Kg. In subacute toxicity study, statistical analysis of hematological and biochemical parameters showed no significant differences compared to control group except marked increase in segmented neutrophils. Histopathological studies revealed no significant structural differences among the treated groups and in comparison to control group. Conclusions: It was concluded that oral administration of doses of ethanolic extract of Calotropis procera flower, administered acutely, did not cause any mortality or notable changes at the dose of 2000 mg/Kg. Therefore, the approximate lethal dose (ALD) of in mice was higher than 2,000 mg/kg. In a 28-day subacute toxicity model, the extract did not cause any mortality, and no treatment-related changes were observed in body weight, organ weight, hematological and biochemical blood analysis, or histopathologic examinations at the extract dose of 2000 mg/Kg. These findings indicate that the no-observed-adverse-effect-level (NOAEL) of Calotropis procera flower ethanolic extract was greater than 2000 mg/kg/day. � 2022Publication Are doctors feeling burnout? - Multicenter cross-sectional study on burnout syndrome and its determinants during the ongoing pandemic(Wolters Kluwer Medknow Publications, 2023) Kumar, Ashutosh; Chawla, Kavita; Mishra, Arun; Singh, Geetu; Pandey, Achyut K.; Rikhari, PraveenBackground: Though the concept of burnout has been around for long, its significance is increasing nowadays owing to the demanding nature of jobs. The latest ICD-11 also provides a detailed description of Burnout syndrome. Physicians are at high risk for experiencing burnout and this becomes especially relevant in the ongoing COVID-19 pandemic. Aim: To determine the risk of burnout among medical faculty and its predictors, if any. Materials and Methods: This was a multicentric cross-sectional study that included medical faculty from four tertiary care government teaching hospitals in north India. A survey was conducted during the current COVID-19 pandemic to assess burnout using a structured online questionnaire based on Burnout Assessment Tool. The questionnaire also included relevant socio-demographic, professional, health, and lifestyle-related details. Descriptive statistics, Mann-Whitney U Test/Kruskal Wallis Test, and Kendall's tau-b Test were used for statistical analysis. Results: A total of 244 medical faculty completed the survey. 27.87% were at risk of burnout, out of which 11.89% were at a very high risk of burnout. Dissatisfaction with the job and dissatisfaction with sleep (P < 0.01 for both) were associated with greater burnout scores and a greater risk of burnout. Conclusion: Faculty members are at high risk of burnout, regardless of sociodemographic and work-related factors. � 2023 Indian Journal of Psychiatry.Publication Clinical Profile and Outcome of COVID-19 Among Immunocompromised Children(Springer, 2021) Rao, Sunil Kumar; Kumar, Ashutosh; Prasad, Rajniti; Gupta, Vineeta; Mishra, Om PrakashThis retrospective study describes the clinical profile, risk of infection and outcome of coronavirus disease-19 in immunocompromised children. It was found that children on immunosuppressant medication has 2.89 times increased risk of infection (P=0.01). Disease manifestation was asymptomatic (P=0.01) or mild with predominant gastrointestinal symptoms (P=0.02) without alteration in immunosuppressive treatment regime. � 2021, Indian Academy of Pediatrics.Publication COVID-19 Mechanisms in the Human Body�What We Know So Far(Frontiers Media S.A., 2021) Kumar, Ashutosh; Narayan, Ravi K.; Prasoon, Pranav; Kumari, Chiman; Kaur, Gurjot; Kumar, Santosh; Kulandhasamy, Maheswari; Sesham, Kishore; Pareek, Vikas; Faiq, Muneeb A.; Pandey, Sada N.; Singh, Himanshu N.; Kant, Kamla; Shekhawat, Prakash S.; Raza, Khursheed; Kumar, SujeetMore than one and a half years have elapsed since the commencement of the coronavirus disease 2019 (COVID-19) pandemic, and the world is struggling to contain it. Being caused by a previously unknown virus, in the initial period, there had been an extreme paucity of knowledge about the disease mechanisms, which hampered preventive and therapeutic measures against COVID-19. In an endeavor to understand the pathogenic mechanisms, extensive experimental studies have been conducted across the globe involving cell culture-based experiments, human tissue organoids, and animal models, targeted to various aspects of the disease, viz., viral properties, tissue tropism and organ-specific pathogenesis, involvement of physiological systems, and the human immune response against the infection. The vastly accumulated scientific knowledge on all aspects of COVID-19 has currently changed the scenario from great despair to hope. Even though spectacular progress has been made in all of these aspects, multiple knowledge gaps are remaining that need to be addressed in future studies. Moreover, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged across the globe since the onset of the first COVID-19 wave, with seemingly greater transmissibility/virulence and immune escape capabilities than the wild-type strain. In this review, we narrate the progress made since the commencement of the pandemic regarding the knowledge on COVID-19 mechanisms in the human body, including virus�host interactions, pulmonary and other systemic manifestations, immunological dysregulations, complications, host-specific vulnerability, and long-term health consequences in the survivors. Additionally, we provide a brief review of the current evidence explaining molecular mechanisms imparting greater transmissibility and virulence and immune escape capabilities to the emerging SARS-CoV-2 variants. Copyright � 2021 Kumar, Narayan, Prasoon, Kumari, Kaur, Kumar, Kulandhasamy, Sesham, Pareek, Faiq, Pandey, Singh, Kant, Shekhawat, Raza and Kumar.Publication COVID-19 vaccination may enhance hippocampal neurogenesis in adults(Academic Press Inc., 2023) Kumar, Ashutosh; Narayan, Ravi K.; Prasoon, Pranav; Jha, Rakesh K.; Kumar, Sujeet; Kumari, Chiman; Pandey, Sada N.; Faiq, Muneeb A.Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It also hints at an added mental health benefit of the COVID-19 vaccination programs in adults. � 2022 Elsevier Inc.Publication Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19(John Wiley and Sons Inc, 2022) Kumar, Ashutosh; Parashar, Rakesh; Kumar, Sujeet; Faiq, Muneeb A; Kumari, Chiman; Kulandhasamy, Maheswari; Narayan, Ravi K.; Jha, Rakesh K.; Singh, Himanshu N.; Prasoon, Pranav; Pandey, Sada N.; Kant, KamlaYoung age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor in the host-cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host-cell entry and the replication of the virus. The putative changes in the virus�host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host-cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry-receptor and the associated proteases, can have more efficient host-cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue-injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine-acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic. � 2021 Wiley Periodicals LLC.Publication Identification and characterization of chickpea genotypes for early flowering and higher seed germination through molecular markers(Springer Science and Business Media B.V., 2022) Yadav, Garima; Jayaswal, Deepanshu; Jayaswall, Kuldip; Bhandawat, Abhishek; Singh, ArvindNath; Tilgam, Jyotsana; Rai, Abhishek Kumar; Chaturvedi, Rachna; Kumar, Ashutosh; Kumar, Sanjay; Jeevan Kumar, S.P.Background: Chickpea is the fourth most important legume crop contributing 15.42% to the total legume production and a rich source of proteins, minerals, and vitamins. Determination of genetic diversity of wild and elite cultivars coupled with early flowering and higher seed germination lines are quintessential for variety improvement. Methods and results: In the present study, we have analyzed the genetic diversity, population structure, cross-species transferability, and allelic richness in 50 chickpea collections using 23 Inter simple sequence repeats (ISSR) markers. The observed parameters such as allele number varied from 3 to 16, range of allele size varied from 150 to 1600�bp and polymorphic information content (PIC) range lies in between 0.15 and 0.49. Dendrogram was constructed with ISSR marker genotypic data and classified 50 chickpea germplasms into groups I and II, where the accession P 74 ? 1 is in group I and the rest are in group II. Dendrogram, Principal component analysis (PCA), dissimilarity matrix, and Bayesian model-based genetic clustering of 50 chickpea germplasms revealed that P 74 ? 1 and P 1883 are very diverse chickpea accessions. Conclusion: Based on genetic diversity analysis, 15 chickpea germplasm having been screened for early flowering and higher seed germination and found that the P 1857-1 and P 3971 have early flowering and higher seed germination percentage in comparison to P 1883 and other germplasm. These agronomic traits are essential for crop improvement and imply the potential of ISSR markers in crop improvement. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.Publication Introduction: Armed forces, society, and culture in colonial South Asia(Taylor and Francis, 2022) Roy, Kaushik; Kumar, Ashutosh[No abstract available]Publication Mycobacterium tuberculosis adaptation to host environment(Elsevier, 2022) Banerjee, Aniruddha; Sengupta, Shatabdi; Nandanwar, Nishant; Pandey, Monika; Tripathi, Deeksha; Pandey, Saurabh; Kumar, Ashutosh; Peddireddy, VidyullathaMycobacterium tuberculosis, a pathogen that causes tuberculosis encounters a variety of stresses and extreme conditions such as acidic conditions, hypoxic and immune system stress, metal, and heat shocks during host infection. It withstands these hostile environments by employing various survival strategies. The lung macrophages are the primary immune cells that interact with M. tuberculosis after infection. Various proteins of M. tuberculosis are responsible for the survival of M. tuberculosis in acidic and hypoxic conditions inside the host. M. tuberculosis tolerates temperature variations with the help of various heat shock proteins (Hsp) such as Hsp70, Hsp22.5, HspR, and the protein Acr2, which is an active member of ?-crystalline family of molecular chaperones. M. tuberculosis also overcomes toxic concentrations of various metal ions. M. tuberculosis fulfills iron requirements by the acquisition of iron using siderophores such as mycobactins and carboxymycobactins. � 2023 Elsevier Inc. All rights reserved.Publication Pharmacokinetic screening to estimate the drug likeliness characteristics of selected herbal anticancer drugs(Research Journal of Pharmacy and Technology, 2023) Singh, Manish; Kumar, Brijesh; Singh, Alok K; Azad, Chandra Shekhar; Yadav, Mukesh K; Kumar, Ashutosh; Kumar, Rajesh; Kumar, Ajay; Chaudhary, PriteeThe pharmacokinetic parameters of a drug plays a very essential role in determining the therapeutic success of an experimental compound, so it is one of the aspects of drug discovery which are essential to be determined in the early phases. The pharmacokinetic studies further help the drug discovery team to optimize their in vivo pharmacokinetic and drug safety bioassays.Low solubility, low absorbency, and chemical instability can seriously affect bioassay results. Today a lot of computational software are available which use their algorithms to calculate the pharmacokinetic parameters of the selected compounds and hence may help the drug discovery team to move in a direction where the chances of getting a good clinical candidate are higher. This paper presents the screening of nine selected herbal anticancer agents (Catechin, Cinnamaldehyde, Epicatechin, Eugenol, Oxyresveratrol, Quercetin, Crocin, Kaempferol, and Emodin) based upon their pharmacokinetic properties with the help of Discovery Studio 2.5. The main parameters which are estimated under this pharmacokinetic ADMET (absorption, distribution, metabolism, excretion and toxicity) study are aqueous solubility, human intestinal absorption, plasma protein binding (PPB), blood-brain-barrier (BBB) penetration, cytochrome P4502D6 inhibition and hepatotoxicity levels. Four compounds (Cinnamaldehyde, Eugenol, Crocin and Oxyresveratrol) were found to possess the required pharmacokinetic properties and are suitable for further anticancer in vivo and in vitro analysis. � RJPT All right reserved.Publication Predicting susceptibility for SARS-CoV-2 infection in domestic and wildlife animals using ACE2 protein sequence homology(Wiley-Liss Inc., 2021) Kumar, Ashutosh; Pandey, Sada N.; Pareek, Vikas; Narayan, Ravi K.; Faiq, Muneeb A.; Kumari, ChimanThe article is presenting a bioinformatics based method predicting susceptibility for SARS-CoV-2 infection in domestic and wildlife animals. Recently, there were reports of cats and ferrets, dogs, minks, golden hamster, rhesus monkeys, tigers, and lions testing for SARS-CoV-2 RNA which indicated for the possible interspecies viral transmission. Our method successfully predicted the susceptibility of these animals for contracting SARS-CoV-2 infection. This method can be used as a screening tool for guiding viral RNA testing for domestic and wildlife animals at risk of getting COVID-19. We provide a list of the animals at risk of developing COVID-19 based on the susceptibility score. � 2020 Wiley Periodicals LLCPublication SARS-CoV-2 Omicron Variant Genomic Sequences and Their Epidemiological Correlates Regarding the End of the Pandemic: In Silico Analysis(JMIR Publications Inc., 2023) Kumar, Ashutosh; Asghar, Adil; Singh, Himanshu N.; Faiq, Muneeb A.; Kumar, Sujeet; Narayan, Ravi K.; Kumar, Gopichand; Dwivedi, Prakhar; Sahni, Chetan; Jha, Rakesh K.; Kulandhasamy, Maheswari; Prasoon, Pranav; Sesham, Kishore; Kant, Kamla; Pandey, Sada N.Background: Emergence of the new SARS-CoV-2 variant B.1.1.529 worried health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. The World Health Organization (WHO) designated this variant as a global variant of concern (VOC), which was named �Omicron.� Following Omicron�s emergence, a surge of new COVID-19 cases was reported globally, primarily in South Africa. Objective: The aim of this study was to understand whether Omicron had an epidemiological advantage over existing variants. Methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period from October 1 to November 29, 2021) with matched epidemiological data (new COVID-19 cases and deaths) from South Africa. Results: Compared with the current list of global VOCs/variants of interest (VOIs), as per the WHO, Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and the RBM. The mutations were found to be primarily condensed in the spike region (n=28-48) of the virus. Further mutational analysis showed enrichment for the mutations decreasing binding affinity to angiotensin-converting enzyme 2 receptor and receptor-binding domain protein expression, and for increasing the propensity of immune escape. An inverse correlation of Omicron with the Delta variant was noted (r=�0.99, P<.001; 95% CI �0.99 to �0.97) in the sequences reported from South Africa postemergence of the new variant, subsequently showing a decrease. There was a steep rise in new COVID-19 cases in parallel with the increase in the proportion of Omicron isolates since the report of the first case (74%-100%). By contrast, the incidence of new deaths did not increase (r=�0.04, P>.05; 95% CI �0.52 to 0.58). Conclusions: In silico analysis of viral genomic sequences suggests that the Omicron variant has more remarkable immune-escape ability than existing VOCs/VOIs, including Delta, but reduced virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the resurgence in COVID-19 cases and its rapid rise as the globally dominant strain. Being more infectious but less lethal than the existing variants, Omicron could have plausibly led to widespread unnoticed new, repeated, and vaccine breakthrough infections, raising the population-level immunity barrier against the emergence of new lethal variants. The Omicron variant could have thus paved the way for the end of the pandemic. � 2023, JMIR Publications Inc.. All rights reserved.Publication South Indian Medicinal Herb: An Extensive Comparison of the Neuroprotective Activity(Bentham Science Publishers, 2022) Singh, Pratistha; Kumar, Ashutosh; Singh, Anil KumarMedicinal Plants have secondary metabolites containing various phytoconstituents. Traditionally, medicinal plants are used in several diseases like cancer, diabetes, neurodegenerative disorder, etc. Flavonoids, Tannin, Phenols, Phenylpropanoids, Isoprenoids, and alkaloids are present in several medicinal plants, which play a very important role to promote health benefits and defensiveness for other disorders. Neurological disorders are prone to the elderly and difficult to treat. Several medicinal plants have been recognized as beneficial in neurological disorders. Various types of plant extract and formulations are present in ancient texts, which are effective in such disorders and should be explored scientifically to mitigate neurodegenerative disorders. In this chapter, we will focus on South Indian medicinal plants which are effective in neurological disorders or have neuroprotective properties. � 2022, Bentham Books imprint. All Rights Reserved.Publication Toxicity (acute and subacute) assessment and in-vivo antiurolithiatic activity of ethanolic extract of Caesalpinia bonducella seed in albino Wistar rat(Open Science Publishers LLP Inc., 2022) Kumar, Ajay; Nandi, Manmath Kumar; Kumar, Brijesh; Kumar, Ashutosh; Kumar, Rajesh; Kailashiya, Vikas; Singh, Ambrish KumarThe objective of the present work is to find supportive evidence for the use of Caesalpinia bonducella in nephrolithiasis. For safety assessment of ethanolic extract of seed of C. bonducella (ECB), acute and subacute oral toxicity studies was performed. In the acute oral toxicity study at a dose of 2,000 mg/kg and subacute oral toxicity study at dose of 250, 500, and 1,000 mg/kg, no changes were seen in the behavior, haematological parameters, biochemical parameters, histopathology of major organ, and body weight of rats. The efficacy of ECB at dose of 200 and 400 mg/kg was studied in ethylene glycol, glycolic acid, and sodium oxalate induced urolithiasis in rats and marketed cystone tablet at a dose of 750 mg/kg was used as the standard drug. The mean body weight difference, urinary parameters (urine pH, urine volume, levels of calcium, magnesium, and phosphorus), and serum biochemical parameters [urea, Blood urea nitrogen (BUN), creatinine, uric acid, and alkaline phosphatase] were measured. Urolithiasis caused a significant decrease in mean body weight, pH, and volume of urine and increased in both serum biochemical parameters and urinary electrolyte concentration as compared with the normal control group. Histopathology of kidneys were showed increased glomerular hypercellularity, hydropic tubular degeneration, and cast in the induced control group. Ethanolic Extract of Caesalpinia bonducella (ECB) was found to be effective to normalise the above all changes. It was concluded that the ECB was effective in the prevention and elimination of calcium oxalate crystal deposition into kidneys. � 2022. Ajay Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).Publication War in Indian languages print: North Indian soldiers and the First World War(Taylor and Francis, 2022) Kumar, Ashutosh[No abstract available]Publication Warfare and society in british India, 1757-1947(Taylor and Francis, 2022) Kumar, Ashutosh; Roy, KaushikThis book explores the intricate and intimate relationship between military organization, imperial policy, and society in colonial South Asia. The chapters in the volume focus on technology, logistics, and state building. The present volume highlights the salient features of expansion and consolidation of imperial control over the subcontinent, and ultimate demise of the Raj. Further, it turns the spotlight on to subaltern challenges to imperialism as well as the role of non-combatants in warfare. � 2023 selection and editorial matter, Ashutosh Kumar and Kaushik Roy. All rights reserved.
