Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against Leptospiral Species: In Silico and In Vitro Approach.

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase-capable of moving inside mitochondria-which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 µg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

Spatial seroprevalence of classical swine fever in India.

Classical swine fever (CSF) is a highly contagious dreadful disease of pigs leading to 100% mortality in acute form in susceptible population thereby causing huge economic loss to pig farmers. This study was undertaken to assess the seroprevalence of CSF at national level. A two-stage random sampling methodology was adopted that included 271 villages from 115 districts of India. A total of 5848 pig serum samples from twenty-five states and one Union Territory of India were collected during 2018-2019. A percent positivity of 38.52 was found at national level. Puducherry and Sikkim showed the highest and lowest percent positivity respectively. Pigs from the west zone showed the highest seroprevalence of 55.83% and those from the south zone showed the lowest of 30.25%. Adult pigs in the north and east zones showed highest percent positivity of 81.8, whereas pigs of more than 3 years of age showed highest percent positivity of 54.9, 75 and 62.5 in the north east, west and central zones respectively. Young ones showed percent positivity of 41.5 in the south zone. Higher rainfall (> 3 mm/day) and lower temperature (< 26 °C) favoured the existence of disease in the north east region combined with high density of pig population. Amidst no fool proof alert system, seroprevalence is the best method to assess the status of CSF in herd/population that provides the policymakers to plan for control of disease.

Development of classical swine fever virus E2-protein based indirect ELISA for detection of antibodies against the virus in pigs.

Classical swine fever (CSF) is an economically important and highly contagious disease of pigs caused by CSF virus, genus Pestivirus. Serological diagnosis of the disease is highly valuable for surveillance and thereby containment of spread of the disease. In this study, we have demonstrated the development of CSFV envelope glycoprotein E2-based indirect ELISA (E2-iELISA) for the detection of CSFV specific antibodies. The full-length E2 protein was expressed in E. coli and the purified protein was used as a coating antigen in indirect ELISA for detecting CSFV specific antibodies in pigs. A panel of 506 pig sera samples was used to validate the ELISA and the results were highly comparable to the results obtained with the commercial antibody detection kit (PrioCHECK CSFV Ab kit). The in-house E2-iELISA demonstrated high diagnostic sensitivity (95.4%) and specificity (95.5%), highlighting its potential application for sero-surveillance or monitoring of the disease in the swine population.

A thirty-year time series analyses identifies coherence between oscillations in Anthrax outbreaks and El Niño in Karnataka, India.

Anthrax is an economically important zoonotic disease affecting both livestock and humans. The disease is caused by a spore forming bacterium, Bacillus anthracis, and is considered endemic to the state of Karnataka, India. It is critical to quantify the role of climatic factors in determining the temporal pattern of anthrax outbreaks, so that reliable forecasting models can be developed. These models will aid in establishing public health surveillance and guide strategic vaccination programs, which will reduce the economic loss to farmers, and prevent the spill-over of anthrax from livestock to humans. In this study, correlation and coherence between time series of anthrax outbreaks in livestock (1987-2016) and meteorological variables and Sea Surface Temperature anomalies (SST) were identified using a combination of cross-correlation analyses, spectral analyses (wavelets and empirical mode decomposition) and further quantified using a Bayesian time series regression model accounting for temporal autocorrelation. Monthly numbers of anthrax outbreaks were positively associated with a lagged effect of rainfall and wet day frequency. Long-term periodicity in anthrax outbreaks (approximately 6-8 years) was coherent with the periodicity in SST anomalies and outbreak numbers increased with decrease in SST anomalies. These findings will be useful in planning long-term anthrax prevention and control strategies in Karnataka state of India.

Comprehensive Spatial-Temporal and Risk Factor Insights for Optimizing Livestock Anthrax Vaccination Strategies in Karnataka, India.

Anthrax, a zoonotic disease affecting both livestock and humans globally, is caused by Bacillus anthracis. The objectives of this study were the following: (1) to identify environmental risk factors for anthrax and use this information to develop an improved predictive risk map, and (2) to estimate spatial variation in basic reproduction number (Ro) and herd immunity threshold at the village level, which can be used to optimize vaccination policies within high-risk regions. Based on the anthrax incidences from 2000-2023 and vaccine administration figures between 2008 and 2022 in Karnataka, this study depicted spatiotemporal pattern analysis to derive a risk map employing machine learning algorithms and estimate Ro and herd immunity threshold for better vaccination coverage. Risk factors considered were key meteorological, remote sensing, soil, and geographical parameters. Spatial autocorrelation and SaTScan analysis revealed the presence of hotspots and clusters predominantly in the southern, central, and uppermost northern districts of Karnataka and temporal cluster distribution between June and September. Factors significantly associated with anthrax were air temperature, surface pressure, land surface temperature (LST), enhanced vegetation index (EVI), potential evapotranspiration (PET), soil temperature, soil moisture, pH, available potassium, sulphur, and boron, elevation, and proximity to waterbodies and waterways. Ensemble technique with random forest and classification tree models were used to improve the prediction accuracy of anthrax. High-risk areas are expected in villages in the southern, central, and extreme northern districts of Karnataka. The estimated Ro revealed 11 high-risk districts with Ro > 1.50 and respective herd immunity thresholds ranging from 11.24% to 55.47%, and the assessment of vaccination coverage at the 70%, 80%, and 90% vaccine efficacy levels, all serving for need-based strategic vaccine allocation. A comparison analysis of vaccinations administered and vaccination coverage estimated in this study is used to illustrate difference in the supply and vaccine force. The findings from the present study may support in planning preventive interventions, resource allocation, especially of vaccines, and other control strategies against anthrax across Karnataka, specifically focusing on predicted high-risk regions.

Spatial and temporal analysis of haemorrhagic septicaemia outbreaks in India over three decades (1987-2016).

Haemorrhagic septicaemia (HS) is an economically important disease affecting cattle and buffaloes and the livelihoods of small-holder farmers that depend upon them. The disease is caused by Gram-negative bacterium, Pasteurella multocida, and is considered to be endemic in many states of India with more than 25,000 outbreaks in the past three decades. Currently, there is no national policy for control of HS in India. In this study, we analysed thirty year (1987-2016) monthly data on HS outbreaks using different statistical and mathematical methods to identify spatial variability and temporal patterns (seasonality, periodicity). There was zonal variation in the trend and seasonality of HS outbreaks. Overall, South zone reported maximum proportion of the outbreaks (70.2%), followed by East zone (7.2%), Central zone (6.4%), North zone (5.6%), West zone (5.5%) and North-East zone (4.9%). Annual state level analysis indicated that the reporting of HS outbreaks started at different years independently and there was no apparent transmission between the states. The results of the current study are useful for the policy makers to design national control programme on HS in India and implement state specific strategies. Further, our study and strategies could aid in implementation of similar approaches in HS endemic tropical countries around the world.

Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials.

Background: Lung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85-90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy. Objective: Our study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group. Methods: We selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually. Results: Patients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis. Conclusion: Docetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized.

Investigating the Influence of ANTXR2 Gene Mutations on Protective Antigen Binding for Heightened Anthrax Resistance.

Bacillus anthracis is the bacterium responsible for causing the zoonotic disease called anthrax. The disease presents itself in different forms like gastrointestinal, inhalation, and cutaneous. Bacterial spores are tremendously adaptable, can persist for extended periods and occasionally endanger human health. The Anthrax Toxin Receptor-2 (ANTXR2) gene acts as membrane receptor and facilitates the entry of the anthrax toxin into host cells. Additionally, mutations in the ANTXR2 gene have been linked to various autoimmune diseases, including Hyaline Fibromatosis Syndrome (HFS), Ankylosing Spondylitis (AS), Juvenile Hyaline Fibromatosis (JHF), and Infantile Systemic Hyalinosis (ISH). This study delves into the genetic landscape of ANTXR2, aiming to comprehend its associations with diverse disorders, elucidate the impacts of its mutations, and pinpoint minimal non-pathogenic mutations capable of reducing the binding affinity of the ANTXR2 gene with the protective antigen. Recognizing the pivotal role of single-nucleotide polymorphisms (SNPs) in shaping genetic diversity, we conducted computational analyses to discern highly deleterious and tolerated non-synonymous SNPs (nsSNPs) in the ANTXR2 gene. The Mutpred2 server determined that the Arg465Trp alteration in the ANTXR2 gene leads to altered DNA binding (p = 0.22) with a probability of a deleterious mutation of 0.808; notably, among the identified deleterious SNPs, rs368288611 (Arg465Trp) stands out due to its significant impact on altering the DNA-binding ability of ANTXR2. We propose these SNPs as potential candidates for hypertension linked to the ANTXR2 gene, which is implicated in blood pressure regulation. Noteworthy among the tolerated substitutions is rs200536829 (Ala33Ser), recognized as less pathogenic; this highlights its potential as a valuable biomarker, potentially reducing side effects on the host while also reducing binding with the protective antigen protein. Investigating these SNPs holds the potential to correlate with several autoimmune disorders and mitigate the impact of anthrax disease in humans.

Application of machine learning models for risk estimation and risk prediction of classical swine fever in Assam, India.

The present study is aimed to develop an early warning system of Classical swine fever (CSF) disease by applying machine learning models and to study the climate-disease relationship with respect to the spatial occurrence and outbreaks of the disease in the north-eastern state of Assam, India. The disease incidence data from the year 2005 to 2021 was used. The linear discriminant analysis (LDA) revealed that significant environmental and remote sensing risk factors like air temperature, enhanced vegetation index, land surface temperature, potential evaporation rate and wind speed were significantly contributing to CSF incidences in Assam. Furthermore, the climate-based disease modelling was applied to relevant ecological and environmental risk factors determined using LDA and risk maps were generated. The western and eastern regions of the state were predicted to be at high risk of CSF with presence of significant hotspots. For the districts that are significantly clustered, the Basic reproduction number (R0) was calculated after the predicted results were superimposed onto the risk maps. The R0 value ranged from 1.04 to 2.07, implying that the eastern and western regions of Assam are more susceptible to CSF. Machine learning models were implemented using R statistical software version 3.1.3. The random forest, classification tree analysis and gradient boosting machine were found to be the best-fitted models for the study group. The models' performance was measured using the Receiving Operating Characteristic (ROC) curve, Cohen's Kappa, True Skill Statistics, Area Under ROC Curve, ACCURACY, ERROR RATE, F1 SCORE, and Logistic Loss. As a part of the suggested study, these models will help us to understand the disease transmission dynamics, risk factors and spatio-temporal pattern of spread and evaluate the efficacy of control measures to battle the economic losses caused by CSF outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00847-6.

Evaluation of codon usage patterns and molecular evolution dynamics in Japanese encephalitis virus: An integrated bioinformatics approach.

In the recent survey, Japanese encephalitis (JE) is one of the most common mosquito-borne diseases, accounting for ∼30% of fatalities. The outbreaks of the JE virus (JEV) suggests that exhaustive study is essential for the prevention and management of the disease. The disease mainly spreads in humans and pigs by the vector: mosquito; as this is a major concern, this study had employed various bioinformatics tools to investigate the codon usage bias, evolutionary inference and selection pressure analysis of the Japanese encephalitis virus disease. The results indicated that the JE virus was biased and natural selection was the main factor shaping the codon usage that was determined and confirmed with the Nc, neutrality, PR2 plots and correlation analysis. The evolutionary analysis revealed that the virus had a substitution rate of 1.54 × 10-4 substitution/site/year and the tMRCA was found to be in 1723. The transmission of the virus in the map found transmissions mostly from China and transmitted across Asia and Africa. The selection pressure analysis employed three methods which had 969th codon site as diversifying site and had many purifying sites that shows the virus had evolved rapidly. The inferences from this study would aid people to employ this methodology on various diseases and also perform insilico studies in the field of vaccinology and immunoinformatics.

Preliminary Evaluation of Lablab purpureus Phytochemicals for Anti-BoHV-1 Activity Using In Vitro and In Silico Approaches.

Lablab purpureus from the Fabaceae family has been reported to have antiviral properties and used in traditional medical systems like ayurveda and Chinese medicine and has been employed to treat a variety of illnesses including cholera, food poisoning, diarrhea, and phlegmatic diseases. The bovine alphaherpesvirus-1 (BoHV-1) is notorious for causing significant harm to the veterinary and agriculture industries. The removal of the contagious BoHV-1 from host organs, particularly in those reservoir creatures, has required the use of antiviral drugs that target infected cells. This study developed LP-CuO NPs from methanolic crude extracts, and FTIR, SEM, and EDX analyses were used to confirm their formation. SEM analysis revealed that the LP-CuO NPs had a spherical shape with particle sizes between 22 and 30 nm. Energy-dispersive X-ray pattern analysis revealed the presence of only copper and oxide ions. By preventing viral cytopathic effects in the Madin-Darby bovine kidney cell line, the methanolic extract of Lablab purpureus and LP-CuO NPs demonstrated a remarkable dose-dependent anti-BoHV-1 action in vitro. Furthermore, molecular docking and molecular dynamics simulation studies of bio-actives from Lablab purpureus against the BoHV-1 viral envelope glycoprotein disclosed effective interactions between all phytochemicals and the protein, although kievitone was found to have the highest binding affinity, with the greatest number of interactions, which was also validated with molecular dynamics simulation studies. Understanding the chemical reactivity qualities of the four ligands was taken into consideration facilitated by the global and local descriptors, which aimed to predict the chemical reactivity descriptors of the studied molecules through the conceptual DFT methodology, which, along with ADMET finding, support the in vitro and in silico results.

Molecular insights into the in silico discovery of corilagin from Terminalia chebula as a potential dual inhibitor of SARS-CoV-2 structural proteins.

The spike (S) glycoprotein and nucleocapsid (N) proteins are the crucial pathogenic proteins of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus during its interaction with the host. Even FDA-approved drugs like dexamethasone and grazoprevir are not able to curb the viral progression inside the host and are reported with adverse effects on body metabolism. In this context, we aim to report corilagin a novel, potential dual inhibitor of S and N proteins from Terminalia chebula. The bioactive compounds of T. chebula were subjected to a series of computational investigations including molecular docking simulations, molecular dynamics (MD) simulations, binding free energy calculations, and PASS pharmacological analysis. The results obtained from these studies revealed that corilagin was highly interactive with the S (-8.9 kcal/mol) and N (-9.2 kcal/mol) proteins, thereby showing dual inhibition activity. It was also found to be stable enough to induce biological activity inside the inhibitor binding pocket of the target enzymes throughout the dynamics simulation run for 100 ns. This is also confirmed by the changes in the protein conformations, evaluated using free energy landscapes. Outcomes from this investigation identify corilagin as the lead potential dual inhibitor of S and N proteins of SARS-CoV-2, which could be taken for biological studies in near future.Communicated by Ramaswamy H. Sarma.

Prevalence of brucellosis in livestock of African and Asian continents: A systematic review and meta-analysis.

Brucellosis is a highly contagious bacterial disease that mainly affects ruminants, but it may affect equines, canines, and felines. The disease is of utmost significance from an economic standpoint in countries where there is no national brucellosis prevention and eradication policy in operation. A systematic review was done to estimate disease burden, incidences, prevalence, and geographical distribution critical in planning appropriate intervention strategies for the control and prevention of Brucellosis. Research articles that were published during the period 2000-2020 were considered for this study after reinforced scrutiny by two independent authors. Meta-regression was used to examine heterogeneity, and subgroup and sensitivity analyses were used to calculate residual heterogeneity and the pooled prevalence of Brucellosis in livestock. Confounders such as geography, a diagnostic test, and species had the greatest R 2 values of 17.8, 8.8, and 2.3%, respectively, indicating the presence of heterogeneity and necessitating more research into sensitivity and subgroup analysis. The combined pooled prevalence of brucellosis in both Asia and African countries was 8% when compared to 12% in the Indian livestock population. The findings of our systematic review and meta-analysis indicate that brucellosis continues to be an important animal and public health concern in developing countries of Asia and Africa, as evidenced by the prevalence rate of brucellosis in these regions. Our findings suggested that well-planned epidemiological surveillance studies in different geographic settings are needed to generate reliable data on disease burden including the economic loss in Asian and African countries.

Prevalence of Methicillin-resistant Staphylococcus Aureus in India: A Systematic Review and Meta-analysis.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has increased and become a serious concern worldwide, including India. Additionally, MRSA isolates are showing resistance to other chemotherapeutic agents. Isolated and valuable reports on the prevalence of MRSA are available in India. There is no systematic review on the prevalence of MRSA in one place; hence, this study was planned. The overall prevalence of MRSA in humans in India was evaluated state-wise, zone-wise, and year-wise. A systematic search from PubMed, Indian journals, Google Scholar, and J-Gate Plus was carried out and retrieved 98 eligible articles published from 2015 to 2020 in India. The statistical analysis of data was conducted using R software. The overall prevalence of MRSA was 37% (95% CI: 32-41) from 2015 to 2019. The pooled prevalence of MRSA zone-wise was 41% (95% CI: 33-50), 43% (95% CI: 20-68), 33% (95% CI: 24-43), 34% (95% CI: 26-42), 36% (95% CI: 25-47), and 40% (95% CI: 23-58) for north, east, west, south, central, and northeast region-zones, respectively. The state-wise stratified results showed a predominance of MRSA in Jammu and Kashmir with 55% (95% CI: 42-67) prevalence, and the lowest was 21% (95% CI: 11-34) in Maharashtra. The study indicated that the prevalence data would help in formulating and strict implementation of control measures in hospital areas to prevent the outbreak of MRSA infection and management of antibiotic usage.

An extensive analysis of Codon usage pattern, Evolutionary rate, and Phylogeographic reconstruction in Foot and mouth disease (FMD) serotypes (A, Asia 1, and O) of six major climatic zones of India: A comparative study.

Foot and mouth disease (FMD) is a major economically important viral disease of cloven-hoofed livestock globally. The FMD virus (FMDV) spreads widely in confined, cool, and humid climatic conditions. Being an RNA virus, FMDV is genetically unstable, and its genome evolution is highly influenced by mutational pressure. The climatic and environmental conditions have a significant impact on mutational pressure. The present study is a primary effort to establish a comprehensive relationship between climatic factors and the molecular evolutionary pattern of serotypes FMDV circulating in India. In this study, isolates of three serotypes (A, Asia 1, and O) were selected from six major climatic zones of India (Montane, Humid subtropical, Tropical wet and dry, Tropical wet, Semi-arid and Arid). Based on the full genome nucleotide sequence data, the codon usage bias, evolutionary and phylogeographic analysis was carried out. The study revealed that the codon use bias indicators in the FMDV serotypes differed significantly depending on the climatic zones. It implies that the selection and mutational pressure influence the codon usage pattern indices, with mutational pressure taking precedence in determining the codon usage bias of the FMDV genome. The tMRCA was estimated to be 1977, 1956, and 1953 for Indian FMD virus serotype-A, Asia 1, and O respectively which is around 32, 60, and 61 years before its actual identification in the field. Based on the evolutionary rates the serotype O is evolving rapidly compare to other serotypes in India. Virus transmission across the region was evident from the phylogeographic analysis. The integrated analysis of codon usage bias, evolutionary rate, and phylogeography analysis signifies the major role of mutational and selection pressure, implying that the FMD virus co-evolution and adaptations are highly influenced by climatic/environmental factors.

Overall Survival Prediction of Docetaxel-based Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis.

Objectives: Non-small cell lung cancer (NSCLC) accounts for 75-85% of all lung cancer diagnoses. This meta-analysis sought to estimate the overall survival (OS) of NSCLC based on randomized control trials which had compared docetaxel with kinase inhibitors, antineoplastic agents, and monoclonal antibodies as second-line chemotherapy for advanced NSCLC. Methods: We selected 18 randomized control trials which used docetaxel as the standard treatment arm, while kinase inhibitors, antineoplastic agents, and monoclonal antibodies constituted the experimental arm. The methodological quality of the trial was classified according to the Modified Jadad score. Several steps were taken to reduce publication bias. A forest plot was used to graphically summarize the meta-analysis. Results: The Hedge's g value of antineoplastic agents was 0.11 (95% CI: -0.03-0.26), while for kinase inhibitors was 0.04 (95% CI: -0.10-0.17) and monoclonal antibodies was 0.05 (95% CI: -0.02-0.13). Forest plot showed a clear though only slightly higher overall survival using docetaxel compared to those of the antineoplastic agents, kinase inhibitors, and monoclonal antibodies, due to the existence of moderate heterogeneity and lower impact. Conclusions: Overall, the patients in these studies who were in the standard (docetaxel) treatment arm had slightly better OS than those in the intervention treatment arm. As per the results, docetaxel was more effective in the second-line treatment of advanced NSCLC than antineoplastic agents, monoclonal antibodies, and kinase inhibitors. We infer that docetaxel-based second-line therapy for patients with advanced NSCLC is supported by our meta-analysis.

The first study on analysis of the codon usage bias and evolutionary analysis of the glycoprotein envelope E2 gene of seven Pestiviruses.

Background and Aim: Pestivirus, a genus of the Flaviviridae family, comprises viruses that affect bovines, sheep, and pigs. Symptoms, including hemorrhagic syndromes, abortion, respiratory complications, and deadly mucosal diseases, are produced in infected animals, which cause huge economic losses to the farmers. Bovine viral diarrhea virus-1, bovine viral diarrhea virus-2, classical swine fever virus, border disease virus, Bungowannah, Hobi-like, and atypical porcine pestivirus belonging to the Pestivirus genus were selected for the study. This study aimed to estimate the codon usage bias and the rate of evolution using the glycoprotein E2 gene. Furthermore, codon usage bias analysis was performed using publicly available nucleotide sequences of the E2 gene of all seven Pestiviruses. These nucleotide sequences might elucidate the disease epidemiology and facilitate the development of designing better vaccines. Materials and Methods: Coding sequences of the E2 gene of Pestiviruses A (n = 89), B (n = 60), C (n = 75), D (n = 10), F (n = 07), H (n = 52), and K (n = 85) were included in this study. They were analyzed using different methods to estimate the codon usage bias and evolution. In addition, the maximum likelihood and Bayesian methodologies were employed to analyze a molecular dataset of seven Pestiviruses using a complete E2 gene region. Results: The combined analysis of codon usage bias and evolutionary rate analysis revealed that the Pestiviruses A, B, C, D, F, H, and K have a codon usage bias in which mutation and natural selection have played vital roles. Furthermore, while the effective number of codons values revealed a moderate bias, neutrality plots indicated the natural selection in A, B, F, and H Pestiviruses and mutational pressure in C, D, and K Pestiviruses. The correspondence analysis revealed that axis-1 significantly contributes to the synonymous codon usage pattern. In this study, the evolutionary rate of Pestiviruses B, H, and K was very high. The most recent common ancestors of all Pestivirus lineages are 1997, 1975, 1946, 1990, 2004, 1990, and 1990 for Pestiviruses A, B, C, D, F, H, and K, respectively. This study confirms that both mutational pressure and natural selection have played a significant role in codon usage bias and evolutionary studies. Conclusion: This study provides insight into the codon usage bias and evolutionary lineages of pestiviruses. It is arguably the first report of such kind. The information provided by the study can be further used to elucidate the respective host adaptation strategies of the viruses. In turn, this information helps study the epidemiology and control methods of pestiviruses.

Prevalence of Japanese encephalitis (JE) virus in mosquitoes and animals of the Asian continent: A systematic review and meta-analysis.

BACKGROUND: Japanese encephalitis (JE) is a viral zoonotic disease that has been found in several countries of Asia and is responsible for high mortality and morbidity of men and animals in rural and sub-urban endemic areas due to the virus re-circulation among diverse hosts and vectors. The present study estimates the prevalence of the JE virus in the vector and animal population of the Asian continent using a systematic review and meta-analysis. METHODS: The Cochran collaborators' Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA] guidelines were used for systematic review and meta-analysis. The heterogeneity was observed in meta-regression analysis due to several factors including region, species, and different diagnostic assays used in various studies. Thus we did sensitivity and subgroup analysis. RESULTS: The prevalence of the JE virus was calculated using a total sample size of 47,391. Subgroup analysis revealed the JE virus prevalence of 39% in the Southeast Asia region, followed by East Asia with 35% and South Asia with 15% prevalence. Hence, the overall pooled prevalence of the JE virus was 26% in the Asian continent. CONCLUSIONS: The highest proportion of infection was found in pigs amongst all animals, reinforcing the fact that they can be used as sentinels to predict outbreaks in humans. The findings of this study will enable researchers and policymakers in better understanding the disease's spatial and temporal distribution, as well as in creating and implementing location-specific JE prevention and control measures.

Seroprevalence of sheeppox and goatpox virus in Asia and African continent: A systematic review and meta-analysis (Scientometrics).

Background and Aim: Two endemic capripox infectious diseases, sheeppox (SP) and goatpox (GP) are common in Asia, Africa, and the Middle East. Sheep and goats, in general, are considered current assets of small and marginal farmers and have significant economic value in terms of meat, wool, and skin/hide production. Sheep and goat populations in India total 148.88 million and 74.26 million, respectively. Capripox caused US$ 2.3 million (Indian Rupee [INR] 105 million) in economic damages in Maharashtra (India) alone, and it took over 6 years for a flock to recover from the outbreak. The projected yearly loss at the national level is US$ 27.47 million (INR 1250 million). As a result, Capripox diseases put small and marginal farmers under much financial strain. The present study estimates the seroprevalence of SP and GP diseases in the Asian and African continents using systematic review and meta-analysis. The results of the study will help researchers and policymakers to understand the spatial and temporal distribution of the disease and its burden. In addition, the results are also helpful to design and implement location-specific prevention and eradication measures against these diseases. Materials and Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines of Cochran collaborations were used for systematic review and subsequently meta-analysis were used. The literature was collected from various databases. Initial search string resulted in more than nine thousand articles for the period 2000 to 2020 using the different combinations of keywords and Boolean operators (or not) asterisk* and quotation marks. Out of 9398 papers, 80 studies were chosen for complete test reviews and quality bias evaluation using the inclusion and exclusion criteria. Finally, 21 articles were used for the meta-analysis. The statistical study employed fixed effects and random effects models using R. Results: Seroprevalence of SP and GP was calculated using studies with a cumulative sample size of 4352, out of which sheep and goats' samples together contribute 48%, followed by sheep (32%) and goat (21%). The result of the meta-regression revealed that detection techniques had a significant impact on the overall effect size at 5% level (Qm=14.12). Subgroup analysis of polymerase chain reaction (PCR) test with samples was further grouped into two categories based on the median, and it revealed that 62% of samples used PCR as a detecting test followed by group-II. Conclusion: From the study, it is concluded that SP and GP diseases are highly prevalent; hence, effective vaccines, proper education to farmers through extension activity, and transboundary disease movement restriction are necessary for the control and eradication of the disease.