Role of ribosomal pathways and comorbidity in COVID-19: Insight from SARS-CoV-2 proteins and host proteins interaction network analysis.

The COVID-19 pandemic has become a significant global issue in terms of public health. While it is largely associated with respiratory complications, recent reports indicate that patients also experience neurological symptoms and other health issues. The objective of this study is to examine the network of protein-protein interactions (PPI) between SARS-CoV-2 proteins and human host proteins, pinpoint the central genes within this network implicated in disease pathology, and assess their viability as targets for drug development. The study adopts a network-based approach to construct a network of 29 SARS-CoV-2 proteins interacting with 2896 host proteins, with 176 host genes being identified as interacting genes with all the viral proteins. Gene ontology and pathway analysis of these host proteins revealed their role in biological processes such as translation, mRNA splicing, and ribosomal pathways. We further identified EEF2, RPS3, RPL9, RPS16, and RPL11 as the top 5 most connected hub genes in the disease-causing network, with significant interactions among each other. These hub genes were found to be involved in ribosomal pathways and cytoplasmic translation. Further a disease-gene interaction was also prepared to investigate the role of hub genes in other disorders and to understand the condition of comorbidity in COVID-19 patients. We also identified 13 drug molecules having interactions with all the hub genes, and estradiol emerged as the top potential drug target for the COVID-19 patients. Our study provides valuable insights using the protein-protein interaction network of SARS-CoV-2 proteins with host proteins and highlights the molecular basis of manifestation of COVID-19 and proposes drug for repurposing. As the pandemic continues to evolve, it is anticipated that investigating SARS-CoV-2 proteins will remain a critical area of focus for researchers globally, particularly in addressing potential challenges posed by specific SARS-CoV-2 variants in the future.

Bernoulli trial under restarts: A comparative study of resetting transitions.

A Bernoulli trial describing the escape behavior of a lamb to a safe haven in pursuit by a lion is studied under restarts. The process ends in two ways: either the lamb makes it to the safe haven (success) or is captured by the lion (failure). We study the first passage properties of this Bernoulli trial and find that only mean first passage time exists. Considering Poisson and sharp resetting, we find that the success probability is a monotonically decreasing function of the restart rate. The mean time, however, exhibits a nonmonotonic dependence on the restart rate taking a minimal value at an optimal restart rate. Furthermore, for sharp restart, the mean time possesses a local and a global minima. As a result, the optimal restart rate exhibits a continuous transition for Poisson resetting while it exhibits a discontinuous transition for sharp resetting as a function of the relative separation of the lion and the lamb. We also find that the distribution of first passage times under sharp resetting exhibits a periodic behavior.

Universal to nonuniversal transition of the statistics of rare events during the spread of random walks.

Through numerous experiments that analyzed rare event statistics in heterogeneous media, it was discovered that in many cases the probability density function for particle position, P(X,t), exhibits a slower decay rate than the Gaussian function. Typically, the decay behavior is exponential, referred to as Laplace tails. However, many systems exhibit an even slower decay rate, such as power-law, log-normal, or stretched exponential. In this study, we utilize the continuous-time random walk method to investigate the rare events in particle hopping dynamics and find that the properties of the hop size distribution induce a critical transition between the Laplace universality of rare events and a more specific, slower decay of P(X,t). Specifically, when the hop size distribution decays slower than exponential, such as e^{-|x|^{ß}} (ß>1), the Laplace universality no longer applies, and the decay is specific, influenced by a few large events, rather than by the accumulation of many smaller events that give rise to Laplace tails.

3D assessment of ear morphology.

Introduction: Auricular reconstruction is a technically challenging and aesthetically demanding procedure as the ear has a complex anatomy. Anthropometry aids in achieving aesthetic ear reconstruction. We considered that implication of stereophotogrammetric technology will lead to a better understanding of human ear morphology. Material and methods: A cross-sectional study was conducted in our institutional OPD in a tertiary health care centre in the Northern part of India.400 people were chosen based on selection criteria. facial scans were done for 3D pictures using Canfield VECTRA® H2 3D imaging device. Study variables were assessed after marking landmarks on the 3D-generated auricular image of an individual. Discussion: This study consisted of 55.5% males and 44.5% females belonging to the age group of 5-25 years (30.3%), 26-40 years (38.8%) and>40 yr (31.0%). Out of 400 cases, the majority had; oval shaped auricle, normally rolled helix, square earlobe; knob shaped tragus. The attached type of earlobe attachment was more in the right auricle (37%) and the partial attachment ear lobe was more in the left side auricle (35.5%). Darwin's tubercle showed more proportion in the case of males. The mean length and width of the auricle & attachment length are higher in males compared to females. Ear Angulation is highest among females. Conclusion: Assessment of ear morphology using technologically sound methods like stereophotogrammetry paves the way for a more quick, reliable and easy-to-use method for understanding ear morphology. Precise assessment of ear morphology using stereophotogrammetry helps in providing more cosmetic and acceptable ear restoration.

Automated bidirectional coupling of multiscale models of aerosol dosimetry: validation with subject-specific deposition data.

Assessing the toxicity of airborne particulate matter or the efficacy of inhaled drug depends upon accurate estimates of deposited fraction of inhaled materials. In silico approaches can provide important insights into site- or airway-specific deposition of inhaled aerosols in the respiratory system. In this study, we improved on our recently developed 3D/1D model that simulate aerosol transport and deposition in the whole lung over multiple breath cycles (J. Aerosol Sci 151:105647). A subject-specific multiscale lung model of a healthy male subject using computational fluid-particle dynamics (CFPD) in a 3D model of the oral cavity through the large bronchial airways entering each lobe was bidirectionally coupled with a recently improved Multiple Path Particle Dosimetry (MPPD) model to predict aerosol deposition over the entire respiratory tract over multiple breaths for four conditions matching experimental aerosol exposures in the same subject from which the model was developed. These include two particle sizes (1 and 2.9 µm) and two subject-specific breathing rates of ~300 ml/s (slow breathing) and ~750 ml/s (fast breathing) at a target tidal volume of 1 L. In silico predictions of retained fraction were 0.31 and 0.29 for 1 µm and 0.66 and 0.62 for 2.9 µm during slow and fast breathing, respectively, and compared well with experimental data (1 µm: 0.31±0.01 (slow) and 0.27±0.01 (fast), 2.9 µm: 0.63±0.03 (slow) and 0.68±0.02 (fast)). These results provide a great deal of confidence in the validity and reliability of our approach.

Activation cross section for the (n,2n) and (n,p) reactions on 103Rh, 48Ti and 52Cr from reaction threshold up to 25 MeV energy region.

Activation and off-line γ-ray spectrometric methods were used to measure the ground and isomeric state (n,2n) reaction cross section for 103Rh at two different neutron energies. The standard 27Al (n,α)24Na reference reaction was used to normalise neutron flux. The proton beam from the 14UD BARC-TIFR Pelletron facility in Mumbai, India, was utilised to create high-energy quasi-monoenergetic neutrons via the 7Li (p,n) reaction. Statistical model calculations including the level density, pre-equilibrium and optical potential model were performed using the TALYS (ver. 1.95) and EMPIRE (ver. 3.2.3) reaction codes. In addition, because of considerable discrepancies in measured data, the literature (n,p) reaction cross section of 52Cr and 48Ti targets were examined theoretically in the present work. The measured cross sections are discussed and compared with the latest evaluated data of the FENDL-3.2b, CENDL-3.2, TENDL-2019, JENDL-5.0, and ENDF/B-VIII.0 libraries, and experimental data based on the EXFOR compilation. The theoretical investigation of the (n,2n) reaction cross section was performed for the ground and isomeric state for the first time from reaction threshold to 25 MeV energies. The experimental data corresponding to the ground, isomeric state and isomeric ratio were reproduced consistently by the theoretical calculations. The present experimental results are good with certain literature data and theoretical values.

Disruption in the regulation of casein kinase 2 in circadian rhythm leads to pathological states: cancer, diabetes and neurodegenerative disorders.

Introduction: Circadian rhythm maintains the sleep-wake cycle in biological systems. Various biological activities are regulated and modulated by the circadian rhythm, disruption of which can result in onset of diseases. Robust rhythms of phosphorylation profiles and abundances of PERIOD (PER) proteins are thought to be the master keys that drive circadian clock functions. The role of casein kinase 2 (CK2) in circadian rhythm via its direct interactions with the PER protein has been extensively studied; however, the exact mechanism by which it affects circadian rhythms at the molecular level is not known. Methods: Here, we propose an extended circadian rhythm model in Drosophila that incorporates the crosstalk between the PER protein and CK2. We studied the regulatory role of CK2 in the dynamics of PER proteins involved in circadian rhythm using the stochastic simulation algorithm. Results: We observed that variations in the concentration of CK2 in the circadian rhythm model modulates the PER protein dynamics at different cellular states, namely, active, weakly active, and rhythmic death. These oscillatory states may correspond to distinct pathological cellular states of the living system. We find molecular noise at the expression level of CK2 to switch normal circadian rhythm to any of the three above-mentioned circadian oscillatory states. Our results suggest that the concentration levels of CK2 in the system has a strong impact on its dynamics, which is reflected in the time evolution of PER protein. Discussion: We believe that our findings can contribute towards understanding the molecular mechanisms of circadian dysregulation in pathways driven by the PER mutant genes and their pathological states, including cancer, obesity, diabetes, neurodegenerative disorders, and socio-psychological disease.

Knowledge and Information Resources about Child Abuse among Government and Private Dental Practitioner in Uttar Pradesh, India.

Background and Aim: To evaluate knowledge, attitude, and information sources about child abuse and neglect (CAN) among dentists in Varanasi district of Uttar Pradesh state, India. Subjects and Methods: A cross-sectional online survey was carried out of dentist working in government and private hospitals in the Varanasi district, Uttar Pradesh State, India (n = 674). The structured questionnaire was sent through electronic mail that contained the consent form, instructions for filling, and returning the questionnaire. The data obtained were systematically compiled and the Chi-square test was applied to test the association. The significance level of P ≤ 0.05 was applied. Results: A maximum number of dental practitioners from the government (81.97%) and private sector (85.98%) were aware of the child protection law. A significant number of government and private dental practitioners were satisfied with their knowledge (p = 0.0092); however, 83.79% suggested that the continuing education programs/courses were important tool to update their knowledge. The girl child was maximum sufferer (p = 0.0056) of CAN. Only 14.08% of practitioners acted on the suspected cases, and a statistical significant relation was observed between the government and private dental practitioners for not taking any action on child abuse and neglect (p = 0.0010). Conclusions: Data from this study may provide a useful contribution to the current limited knowledge about the familiarity of dental practitioners with child maltreatment and their skills to recognize and manage CAN cases in their practice. The majority of dental practitioners knew about the child protection law in India, but they were reluctant to report such cases due to the fear of anger from the parents and family of the child. Continuing education programs/courses were the most preferred method for increasing the knowledge regarding CAN. They should report the CAN cases to local legislators and health authorities so to prevent child abuse and neglect from ever occurring.

Adverse Events Following Immunization Among Children Under Two Years of Age: A Prospective Observational Study From North India.

BACKGROUND: Vaccination is one of the most cost-effective child survival health interventions. A single serious adverse event following immunization (AEFI) or a cluster of events may lead to a loss of public confidence in the program and a major setback to immunization coverage. This study was conducted to assess the incidence of AEFIs in children less than two years of age. MATERIAL AND METHODS: A prospective community-based observational study was conducted in the North Indian state of Uttarakhand from October 2017 to February 2018. A total of 255 children who attended the selected sub-centres for immunization were finally included in the study. Follow-up home visits on the 8th and 30th day of vaccination were carried out to identify any occurrences of AEFIs. RESULTS: Among 255 children, 212 AEFIs from 152 vaccinated subjects were reported. The majority of the AEFIs were reported in the age group 0-1 years. The incidence of AEFIs was 33.0 per 100 doses of vaccines administered. The most common AEFI reported was fever (101, 47.6%), followed by swelling (53, 25.0%). Among the vaccines, Pentavalent + oral polio vaccine (OPV) (48.8 per 100 doses) was majorly responsible for AEFIs, followed by diphtheria pertussis tetanus (DPT) + measles and rubella (MR) + OPV (46.6 per 100 doses). CONCLUSION: Our findings revealed that although the incidence of AEFI reported was high, all of them were minor and no serious AEFIs were identified. The awareness among health professionals and the public regarding the reporting of AEFIs should be continued to increase the safety profile of vaccines.

Clinico-Microbiological Profile and Clinical Predictor of Urinary Tract Infection in Children: A Single-Center Study From Himalayan Foothills.

BACKGROUND:  Urinary tract infection (UTI) in children is one of the commonest bacterial infections seen in the pediatric population. Clinical presentation ranges from fever with or without focus and isolation of microbiological agents streamline the treatment. Moreover, local/regional microbial profiles are helpful in antibiotic selection, we conducted a study to assess the prevalence of urine culture positivity in a suspected case of UTI. In addition, antibiotic susceptibility patterns and ultrasonography (USG) finding in culture-positive patients were also studied. METHODS AND MATERIALS: It is a prospective observational study comprising symptomatic children aged one month to 18 years presenting to the outpatient department (OPD), inpatient department (IPD), and the emergency department of Pediatrics with UTI during the period of September 2019 to September 2020. The recorded variables were demographic, clinical presentation, anthropometry, physical examination, blood biochemistry, and outcome. Urine samples were collected and processed as per standard protocols. USG was done for all culture-positive children. Data were presented as frequency, mean (SD) and parametric and non-parametric data were analyzed by Wilcoxon-Mann-Whitney U Test, Chi-Squared Test, or Fisher's Exact Test.  Results: Of the total 354 children, 202 (57.1%) were male and the prevalence of UTI was 64 (18.1%). E. coli (70.3%) was the commonest isolated organism followed by Klebsiella spp (15.6%) and Pseudomonas spp (7%) respectively. The mean (SD) age (months) of presentation of symptoms was significantly lower in culture-positive children as compared to [ 83.49 (58.96) vs 110.10 (58.60); p=0.001] culture-negative children. Fever (96.6%) followed by dysuria (20.1%) were the most common symptoms presented for UTI however dysuria (p=0.003), pus cells (p<0.0001), and RBCs (p=0.002) were significantly present in culture positive children. This study shows increased resistance to third generation of cephalosporins. This study revealed significant differences among various groups (organism growth in positive culture) and the Antibiotic susceptibility test (AST) with a p-value of <0.001.  Conclusion: The prevalence of culture-positive UTI was similar to the reported literature and the presence of fever, dysuria, pus cells, and RBC in urine were commonly observed in the lower age group. Amikacin can be used in suspected UTIs with cephalosporin as empirical antibiotics in the Himalayan Foothills region.

Genomic characterization of Lumpy Skin Disease virus (LSDV) from India: Circulation of Kenyan-like LSDV strains with unique kelch-like proteins.

Lumpy skin disease (LSD) is an economically important poxviral disease endemic to Asia, Europe, and Africa. Recently, LSD has spread to naïve countries, including India, China, Bangladesh, Pakistan, Myanmar, Vietnam, and Thailand. Here, we describe the complete genomic characterization of LSDV from India, LSDV-WB/IND/19 isolated from an LSD affected calf in 2019 determined by Illumina next-generation sequencing (NGS). The LSDV-WB/IND/19 has a genome size of 150,969 bp encoding 156 putative ORFs. Phylogenetic analysis based on complete genome sequence suggested that LSDV-WB/IND/19 is closely related to Kenyan LSDV strains with 10-12 variants with non-synonymous changes confined to LSD_019, LSD_049, LSD_089, LSD_094, LSD_096, LSD_140, and LSD_144 genes. In contrast to complete kelch-like proteins in Kenyan LSDV strains, LSDV-WB/IND/19 LSD_019 and LSD_144 genes were found to encode truncated versions (019a, 019b, and 144a, 144b). LSD_019a and LSD_019b proteins of LSDV-WB/IND/19 resemble that of wild-type LSDV strains based on SNPs and the C-terminal part of LSD_019b except for deletion at K229, whereas the LSD_144a and LSD_144b proteins resemble that of Kenyan LSDV strains based on SNPs, however, C-terminal part of LSD_144a resembles that of vaccine-associated LSDV strains due to premature truncation. The NGS findings were confirmed by Sanger sequencing of these genes in Vero cell isolate as well as in the original skin scab along with similar findings in another Indian LSDV from scab specimen. LSD_019 and LSD_144 genes are thought to modulate virulence and host range in capripoxviruses. This study demonstrates the circulation of unique LSDV strains in India and highlights the importance of constant monitoring of the molecular evolution of LSDV and associated factors in the region in light of the emergence of recombinant LSDV strains.

Glucometrics in the first week of critical illness and its association with mortality.

OBJECTIVE: Evaluation of glucometrics in the first week of ICU stay and its association with outcomes. DESIGN: Prospective observational study. SETTING: Mixed ICU of teaching hospital. PATIENTS: Adults initiated on insulin infusion for 2 consecutive blood glucose (BG) readings ≥180mg/dL. MAIN VARIABLES OF INTEREST: Glucometrics calculated from the BG of first week of admission: hyperglycemia (BG>180mg/dL) and hypoglycemia (BG<70mg/dL) episodes; median, standard deviation (SD) and coefficient of variation (CV) of BG, glycemic lability index (GLI), time in target BG range (TIR). Factors influencing glucometrics and the association of glucometrics to patient outcomes analyzed. RESULTS: A total of 5762 BG measurements in 100 patients of median age 55 years included. Glucometrics: hyperglycemia: 2253 (39%), hypoglycemia: 28 (0.48%), median BG: 169mg/dL (162-178.75), SD 31mg/dL (26-38.75), CV 18.6% (17.1-22.5), GLI: 718.5 [(mg/dL)2/h]/week (540.5-1131.5) and TIR 57% (50-67). Diabetes and higher APACHE II score were associated with higher SD and CV, and lower TIR. On multivariate regression, diabetes (p=0.009) and APACHE II score (p=0.016) were independently associated with higher SD. Higher SD and CV were associated with less vasopressor-free days; lower TIR with more blood-stream infections (BSI). Patients with higher SD, CV and GLI had a higher 28-day mortality. On multivariate analysis, GLI alone was associated with a higher mortality (OR 2.99, p=0.04). CONCLUSIONS: Glycemic lability in the first week in ICU patients receiving insulin infusion is associated with higher mortality. Lower TIR is associated with more blood stream infections.

Genome-wide detection of copy number variations in Tharparkar cattle.

Copy number variations (CNVs) are major forms of genetic variation with an increasing importance in animal genomics. This study used the Illumina BovineSNP 50 K BeadChip to detect the genome-wide CNVs in the Tharparkar cattle. With the aid of PennCNV software, we noticed a total of 447 copy number variation regions (CNVRs) across the autosomal genome, occupying nearly 2.17% of the bovine genome. The average size of detected CNVRs was found to be 122.2 kb, the smallest CNVR being 50.02 kb in size, to the largest being 1,232.87 Kb. Enrichment analyses of the genes in these CNVRs gave significant associations with molecular adaptation-related Gene Ontology (GO) terms. Most CNVR genes were significantly enriched for specific biological functions; signaling pathways, sensory responses to stimuli, and various cellular processes. In addition, QTL analysis of CNVRs described them to be linked with economically essential traits in cattle. The findings here provide crucial information for constructing a more comprehensive CNVR map for the indigenous cattle genome.

Is mucormycosis the end? A comprehensive management of orbit in COVID associated rhino-orbital-cerebral mucormycosis: preserving the salvageable.

BACKGROUND: Rhino-orbital-cerebral mucor mycosis (ROCM) is a relatively rare opportunistic infection caused by the Mucorales species. While ROCM suggests involvement of the paranasal sinuses, orbit and brain ROM (rhino-orbital-Mucormycosis) stands for the fungal invasion in sinuses and orbit sans cerebral involvement. In India with the outbreak of the second COVID wave and the delta variant of the virus, there has been a steep increase in this opportunistic fulminant fungal infection, named COVID-associated Mucor mycosis (CAM). The most critical question in orbital management is when to go ahead with an exenteration. Our study aims to design a pertinent minimal invasive surgical protocol for surgeons to manage such cases based on our surgical experience and mitigate the need for exenteration and save the eyes wherever possible. METHODS: The study is a retrospective analysis of patients of ROM with and without brain involvement, who underwent minimal surgical management between March 2021 to March 2022 along with their follow-up. RESULTS: There were 184 eyes of 148 patients diagnosed with CAM. The mean age was 51.7 years with a male predominance of 103 (70%). All patients developed ROM following the COVID-19 infection and the duration between diagnosis of COVID-19 and ROM was 36 ± 23 days. 18 cases (12%) were bilateral. 76 eyes (41%) had no vision at the presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (61%), cavernous sinus involvement (53%), and central nervous system (CNS) involvement (47%). All the patients (100%) were treated with systemic Liposomal amphotericin-B and sinus debridement. Endoscopic debridement of the orbital disease was performed in 45 (30.4%) cases, 15(8.1%) eyes underwent exenteration and were later rehabilitated with a customized ocular prosthesis, 103 (56%) eyes underwent transcutaneous retrobulbar amphotericin-B. At a mean follow-up of 13.1 months; the complete resolution was seen in 25 (17%) cases, the residual stable lesion was seen in 77(52%) of the cases and new lesions were developed in 13(9%) of the cases. Mortality was seen in 33 (22%) patients and all of them had CNS involvement. CONCLUSIONS: Systemic and protocol-based management can save the life and salvage the eyes.

Influence of alveolar mixing and multiple breaths of aerosol intake on particle deposition in the human lungs.

Predictive dosimetry models play an important role in assessing health effect of inhaled particulate matter and in optimizing delivery of inhaled pharmaceutical aerosols. In this study, the commonly used 1D Multiple-Path Particle Dosimetry model (MPPD) was improved by including a mechanistically based model component for alveolar mixing of particles and by extending the model capabilities to account for multiple breaths of aerosol intake. These modifications increased the retained fraction of particles and consequently particle deposition predictions in the deep lung during tidal breathing. Comparison with an existing dataset (J. Aerosol Sci., 99:27-39, 2016) obtained under two breathing conditions referred to as slow and fast breathing showed significant differences in 1 µm particle deposition between predictions based on subject-specific breathing patterns and lung volume (slow: 30 ± 1%, fast: 21 ± 1%, (average ± standard deviation), N = 7) and measurements (slow: 43 ± 9%, fast: 30 ± 5%) when the prior version of MPPD (single breath and no mixing, J. Aerosol Sci., 151:105647, 2021) was used. Adding a mixing model and multiple breaths moved the predictions (slow: 34 ± 2%, fast:25 ± 2%) closer to the range of deposition measurements. For 2.9 µm particles, predictions from both the original (slow: 70 ± 2%, fast: 57 ± 2%) and the revised MPPD model (slow: 71 ± 2%, fast: 59 ± 3%) compared well with experiments (slow: 67 ± 8%, fast: 58 ± 10%). This was expected as suspended fraction of 2.9 µm particles was small and thus the addition of alveolar mixing and multi breath capability only slightly increased the retained fraction for particles of this size and greater. The revised 1D model improves dose predictions in the deep lung and support human risk assessment from exposure to airborne particles.

Efficacy of Platysma myocutaneous Flap in Oral Defects.

Introduction: Clinicians are baffling for reconstruction of small- to medium-sized defects of the oral cavity since time immemorial, each and every flap has its own limitations, ideal flap should be pliable, easily transferrable that can result in a better restoration of form and function of oral mucosa, we have platysma for the same purpose. Aims: We aim to provide surgical technique of the superiorly-based platysma myocutaneous flap with a single neck incision in this study, as well as the flap design, results, and complications associated with age, gender, the recipient site, and the size of the defect. Materials and methods: Study included 20 patients with oral potentially malignant disorders operated under local anaesthesia with wide local excision and reconstruction with platysma myocutaneous flap at a single tertiary care centre. Statistical Analysis: The association between the variables was calculated using Chi-square tests and paired t tests. P < .05 was considered significant. Results: Five cases of dehiscence were found at varied sites and flap viability was significantly influenced by location of skin paddle. In between anterior jugular vein and posterior external jugular vein it was 100% viable while on and posterior to the vein, had skin paddle loss. Significant improvement in mouth opening was also seen in Oral Sub-mucous Fibrosis patients. Conclusion: The platysma flap is a technique sensitive, and its results are promising for the reconstruction of oral defects.

Can dual staining with p16 and Ki67 be biomarkers of epithelial dysplasia in oral lesions?

Background: Oral carcinogenesis is a multistage process with epithelial dysplasia as a premalignant condition. There is a significant inter-observer variation in diagnosing and grading the oral epithelial dysplasia. As human papillomavirus (HPV) is believed to have à strong relationship with oral carcinogenesis, using P16 as a biomarker may help in identifying the cells which may be undergoing the malignant transformation. However, due to the low specificity of P16, dual staining test P16INK4/Ki67 might be a better promising marker for identifying the transformed cells. This study was designed to evaluate the dual expression of P16 and Ki67 as a promising biomarker for dysplasia and their correlation with clinicopathological factors. Materials and Methods: Immunohistochemical analysis for p16 and ki67 was performed on 30 premalignant oral lesions and 36 oral squamous cell carcinoma (OSCC) by dual staining using the CINtec PLUS kit. Results: CINtec positivity was observed only in leukoplakia with dysplasia (46.7%) and squamous cell carcinoma (25%). None of the cases of leukoplakia without dysplasia or oral submucosal fibrosis stained positive for CINtec plus staining. In leukoplakia with dysplasia, there was no significant association with any of the clinicopathological parameters studied. In OSCC cases, alcohol intake showed statistically significant association with CINtec positivity. Conclusion: P16INK4/Ki67 assessment by dual staining is a promising biomarker for identifying dysplasia in cases with diagnostic dilemmas.

Development of High Yielding Fusarium Wilt Resistant Cultivar by Pyramiding of "Genes" Through Marker-Assisted Backcrossing in Chickpea (Cicer arietinum L.).

Pusa 391, a mega desi chickpea variety with medium maturity duration is extensively cultivated in the Central Zone of India. Of late, this variety has become susceptible to Fusarium wilt (FW), which has drastic impact on its yield. Presence of variability in the wilt causing pathogen, Fusarium oxysporum f.sp. ciceri (foc) across geographical locations necessitates the role of pyramiding for FW resistance for different races (foc 1,2,3,4 and 5). Subsequently, the introgression lines developed in Pusa 391 genetic background were subjected to foreground selection using three SSR markers (GA16, TA 27 and TA 96) while 48 SSR markers uniformly distributed on all chromosomes, were used for background selection to observe the recovery of recurrent parent genome (RPG). BC1F1 lines with 75-85% RPG recovery were used to generate BC2F1. The plants that showed more than 90% RPG recovery in BC2F1 were used for generating BC3F1. The plants that showed more than 96% RPG recovery were selected and selfed to generate BC3F3. Multi-location evaluation of advanced introgression lines (BC2F3) in six locations for grain yield (kg/ha), days to fifty percent flowering, days to maturity, 100 seed weight and disease incidence was done. In case of disease incidence, the genotype IL1 (BGM 20211) was highly resistant to FW in Junagarh, Indore, New Delhi, Badnapur and moderately resistant at Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM20211) was the most stable genotype at Junagadh, Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM 20211) and IL4(BGM 20212) were the top performers in yield and highly stable across six environments and were nominated for Advanced Varietal Trials (AVT) of AICRP (All India Coordinated Research Project on Chickpea) in 2018-19. BGM20211 and BGM 20212 recorded 29 and 28.5% average yield gain over the recurrent parent Pusa 391, in the AVT-1 and AVT-2 over five environments. Thus, BGM20211 was identified for release and notified as Pusa Manav/Pusa Chickpea 20211 for Madhya Pradesh, Gujarat and Maharashtra, Southern Rajasthan, Bundhelkhand region of Uttar Pradesh states by the Central Sub-Committees on Crop Standards, Notification and Release of Varieties of Agricultural Crops, Ministry of Agriculture and Farmers Welfare, Government of India, for commercial cultivation in India (Gazette notification number S.O.500 (E) dt. 29-1-2021).Such pyramided lines give resilience to multiple races of fusarium wilt with added yield advantage.

Detection of DDoS Vulnerability in Cloud Computing Using the Perplexed Bayes Classifier.

Cloud computing security has been a critical issue with its increase in demand. One of the most challenging problems in cloud computing is detecting distributed denial-of-service (DDoS) attacks. The attack detection framework for the DDoS attack is tricky because of its nonlinear nature of interruption activities, atypical system traffic behaviour, and many features in the problem space. As a result, creating defensive solutions against these attacks is critical for mainstream cloud computing adoption. In this novel research, by using performance parameters, perplexed-based classifiers with and without feature selection will be compared with the existing machine learning algorithms such as naïve Bayes and random forest to prove the efficacy of the perplexed-based classification algorithm. Comparing the performance parameters like accuracy, sensitivity, and specificity, the proposed algorithm has an accuracy of 99%, which is higher than the existing algorithms, proving that the proposed algorithm is highly efficient in detecting the DDoS attacks in cloud computing systems. To extend our research in the area of nature-inspired computing, we compared our perplexed Bayes classifier feature selection with nature-inspired feature selection like genetic algorithm (GA) and particle swarm optimization (PSO) and found that our classifier is highly efficient in comparison with GA and PSO and their accuracies are 2% and 8%, respectively, less than those of perplexed Bayes classifier.