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Despite their vulnerability to competent forgers, signatures are one of the most widely used user verification methods. Recent research has revealed that EEG signals are harder to reproduce and give superior biometric information. This study aims to improve the effectiveness of person authentication by using deep learning techniques on electroencephalogram (EEG) signals. The broad implementation of EEG-based authentication systems has been hindered by problems such as noise, variability, and inter-subject variances despite the potential distinctiveness of EEG signals. We propose a multiscale convolutional neural network (CNN) and a Bidirectional LSTM (BiLSTM) model called CNN-BiLSTM to extract features and classify raw EEG data. This methodology involves acquiring raw EEG data, preprocessing for noise reduction, standardization, normalization, and employing deep learning techniques for feature extraction and classification. Experimental results exhibit a notable improvement in accuracy and reliability compared to existing EEG authentication methods such as LOF, CNN, FCN, EfficientNet-B0, and BiLSTM. The results showcase the performance of the proposed deep learning model utilizing established metrics such as precision, sensitivity, specificity, and accuracy. The proposed methodology outperforms existing methods and achieves a training and validation accuracy of 98.9% and 92.2%, respectively. The findings of the research demonstrate that the proposed approach has been successful in achieving highly effective results by using EEG signals for the purpose of resolving issues related to person identification.

Abstract Major research interests on quantum key distribution (QKD) are primarily focused on increasing 1. Point-to-point transmission distance (1000 km). 2. Secure key rate (Mbps). 3. Security of quantum layer (device-independence). It is great to push the boundaries in these fronts but these isolated approaches are neither scalable nor cost-effective due to requirements of specialised hardware and different infrastructure. Current and future QKD network requires addressing different set of challenges apart from distance, key rate and quantum security. In this regard, we present ChaQra—a sub quantum network with core features as 1. Crypto agility (integration in the already deployed telecommunication fibres). 2. Software defined networking (SDN paradigm for routing different nodes). 3. reliability (addressing denial-of-service with hybrid quantum safe cryptography). 4. upgradability (modules upgradation based on scientific and technological advancements). 5. Beyond QKD (using QKD network for distributed computing, multi-party computation etc). Our results demonstrate a clear path to create and accelerate quantum secure Indian subcontinent under national quantum mission.

Abstract Handwritten signatures in biometric authentication leverage unique individual characteristics for identification, offering high specificity through dynamic and static properties. However, this modality faces significant challenges from sophisticated forgery attempts, underscoring the need for enhanced security measures in common applications. To address forgery in signature-based biometric systems, integrating a forgery-resistant modality, namely, noninvasive electroencephalography (EEG), which captures unique brain activity patterns, can significantly enhance system robustness by leveraging multimodality’s strengths. By combining EEG, a physiological modality, with handwritten signatures, a behavioral modality, our approach capitalizes on the strengths of both, significantly fortifying the robustness of biometric systems through this multimodal integration. In addition, EEG’s resistance to replication offers a high-security level, making it a robust addition to user identification and verification. This study presents a new multimodal SignEEG v1.0 dataset based on EEG and hand-drawn signatures from 70 subjects. EEG signals and hand-drawn signatures have been collected with Emotiv Insight and Wacom One sensors, respectively. The multimodal data consists of three paradigms based on mental, & motor imagery, and physical execution: i) thinking of the signature’s image, (ii) drawing the signature mentally, and (iii) drawing a signature physically. Extensive experiments have been conducted to establish a baseline with machine learning classifiers. The results demonstrate that multimodality in biometric systems significantly enhances robustness, achieving high reliability even with limited sample sizes. We release the raw, pre-processed data and easy-to-follow implementation details.

Purpose: To report a rare case of a pediatric dacryolith masquerading as congenital nasolacrimal duct obstruction (CNLDO). Observations: A two-year-old male child presented with history of intermittent epiphora and discharge since the age of six months. Clinical evaluation demonstrated raised tear meniscus height and delayed fluorescein dye disappearance test in the right eye. Lacrimal irrigation of the right eye under general anesthesia demonstrated 90 % regurgitation (subjectively) of mucoid fluid with a hard stop. Nasal endoscopy examination demonstrated a dacryolith obstructing the opening of the nasolacrimal duct (NLD) in the inferior meatus. The dacryolith was teased out of the NLD and following its removal the lacrimal irrigation was freely patent. At six-months post operative follow up, epiphora resolved and the child was asymptomatic. Conclusions and importance: While cases of canaliculitis is uncommon in pediatric age group, it is rare to find a NLD dacryolith in a toddler. To the best of the authors’ knowledge, there are few prior reports on pediatric NLD dacryolith masquerading as CNLDO in a toddler (1–3 years).

Abstract Background Pituitary adenomas comprise clinical and pathological characteristics of functional and non-functional subtypes. To enhance our understanding of diagnostic presentations, our study aimed to know the clinicopathological characteristics of pituitary adenomas of both functional and non-functional subtypes. The purpose of our study was to investigate the clinicopathological characteristics of pituitary adenomas, including demographic characteristics, clinical presentations, hormone secretion patterns, invasiveness, and cellular characteristics. Methods A total of 41 cases of pituitary adenomas were analyzed, with 63.4% classified as non-functional adenomas (NFPA) and 36.6% as functional adenomas (FPA). Clinical presentations vary, with vision loss and headaches commonly occurring in both NFPA and FPA. In FPAs, serum hormone levels varied and were categorized into growth hormone-secreting (53.3%), ACTH-secreting (26.7%), PRL-secreting (13.3%), and FSH-secreting (6.7%) subtypes. Moreover, clinical presentations in FPA included diplopia, giddiness, vomiting, ptosis, and limb weakness. Clinical features varied across subtypes, with acromegaly in growth hormone-secreting adenomas, moon facies and weight gain in ACTH-secreting adenomas, poor facial growth in PRL-secreting adenomas, and vision loss in FSH-secreting adenomas. Meanwhile, NFPA were predominantly macroadenomas (88.5%) and exhibited various morphological patterns. Results The proliferation index is higher in functional adenomas (mean 1.32) as compared to non-functional (mean 0.91). Clinical presentations varied across functional and non-functional adenomas. Growth hormone-secreting adenomas were the most common functional subtype, while LH and null cell adenomas were common non-functional subtypes. Two cases were invasive adenomas with a low Ki67 index. Sheets were the most common morphological pattern. PCA analysis revealed significant differences between the two groups, with PC 1 explaining 92.111% of the variance. Conclusions Our study elucidates the clinicopathological characteristics of pituitary adenomas, highlighting significant differences between functional and non-functional subtypes. These findings underscore the importance of tailored diagnostic and management strategies to optimize outcomes for patients with pituitary adenomas.

Abstract Background The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. Results The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. Conclusion Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications. Graphical Abstract

Abstract This paper presents a naïve back propagation (NBP) based $$i\cos \emptyset$$ i cos ∅ technique implemented to a cascaded multilevel inverter (MLI) based shunt active power filter (SAPF). The recommended control algorithm is applied to extract the fundamental component of load current and to decide the compensating current reference for harmonic elimination. The performance of the SAPF using the proposed NBP-based $$i\cos \emptyset$$ i cos ∅ technique is compared with another two classical control techniques, such as, $$i_{d} - i_{q}$$ i d - i q technique and $$i\cos \emptyset$$ i cos ∅ technique. The accuracy of the proposed control technique depends on the tuned estimation of active and reactive weights. The performance study of the proposed SAPF with the proposed control technique is investigated under non-linear conditions, with balanced and unbalanced loading conditions. The results reveal that the recommended SAPF is efficient enough to reduce the harmonics from the source current with smooth variation in DC link voltage. The effectiveness of the proposed method is validated by simulation using MATLAB Simulink, and the real-time results are also validated by the experimental setup.

Fungal diseases, caused mainly by Bipolaris spp., are past and current threats to Northern Wild Rice (NWR) grain production and germplasm preservation in both natural and cultivated settings. Genetic resistance against the pathogen is scarce. Toward expanding our understanding of the global gene communications of NWR and Bipolaris oryzae interaction, we designed an RNA sequencing study encompassing the first 12 h and 48 h of their encounter. NWR activated numerous plant recognition receptors after pathogen infection, followed by active transcriptional reprogramming of signaling mechanisms driven by Ca2+ and its sensors, mitogen-activated protein kinase cascades, activation of an oxidative burst, and phytohormone signaling-bound mechanisms. Several transcription factors associated with plant defense were found to be expressed. Importantly, evidence of diterpenoid phytoalexins, especially phytocassane biosynthesis, among expression of other defense genes was found. In B. oryzae, predicted genes associated with pathogenicity including secreted effectors that could target plant defense mechanisms were expressed. This study uncovered the early molecular communication between the NWR–B. oryzae pathosystem, which could guide selection for allele-specific genes to boost NWR defenses, and overall aid in the development of more efficient selection methods in NWR breeding through the use of the most virulent fungal isolates.

Introduction: The cervix is the lower cylindrical part of the Uterus which projects into the vagina. The cervix despite being a small part, is home to numerous disease conditions, including both neoplastic and non-neoplastic ones. Important among these conditions are Inflammatory conditions like Chronic cervicitis along with premalignant and malignant conditions like CIN and SCC. Most cervical cancers are caused by HPV, an oncogenic virus. The main objective of our study is to analyze the histopathological spectrum of different types of cervical lesions, both neoplastic and non-neoplastic. Methodology: A retrospective study was done on 380 hysterectomy specimens and cervical biopsies that were submitted to the Department of Pathology, Nalanda Medical College and Hospital, Patna from May 2022 to July 2023. Detailed histopathological assessment of various lesions of the cervix was done, including both non-neoplastic as well as neoplastic. Results: Out of 380 cases that were taken into consideration, 340 (89.5%) had non-neoplastic lesions, and 40 (10.5%) had neoplastic lesions. 241 cases (63.4%) were that of Chronic non-specific cervicitis. Other non-neoplastic lesions were Chronic papillary endocervicitis, endocervical polyps, squamous metaplasia, and nabothian cysts. Nearly 14 cases (3.7%) were that of CIN 1, 10 (2.6%) had CIN 2, 3 (0.8%) had CIN 3, and 11 (2.9%) had SCC. 43 years was the mean age of the women with preinvasive lesions. The mean age of patients with SCC was 49.2 years. Conclusion: Chronic non-specific cervicitis was the most common disease condition affecting the cervix, comprising 63.4% of total cases. Neoplasms comprised 10.5% of all cervical lesions. Accurate histopathological diagnosis may help in the reduction of complications caused by chronic cervicitis. The accurate and timely diagnosis of premalignant conditions by histopathology may help in preventing disease progression and avoiding more invasive surgeries thereby reducing morbidity and improving their quality of life.

AbstractObjective Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed ‘heat-targeted, on-demand’ antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection.Methods CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat’s femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40–42 °C (∼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses.Results CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at ∼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted.Conclusion HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.

In-situ vaccination (ISV) utilizing nanoparticles (NPs) and therapeutic devices like focused ultrasound (FUS) can trigger immune-mediated killing of both treated and untreated cancer cells. However, the impact of confounding factors such as aging and gut microbiota composition on therapeutic outcomes remains poorly understood. In this study, we sequentially treated young mice (∼8 weeks) and old mice (>18 months) with bilateral melanoma using FUS and calreticulin nanoparticles (CRT-NP) to enhance immunogenic cell death. The combination of CRT-NP and FUS (CFUS) demonstrated greater efficacy in inducing regression of treated and untreated tumors in young mice compared to old mice. The diminished effectiveness in older mice was associated with significant differences in gut microbiome composition, characterized by alterations in bacterial species and splenic immune cells. Specifically, young mice exposed to CFUS exhibited higher abundance of Bacteroidetes and Verrucomicrobia, which was not observed in the aged cohorts. Turicibacter, Anaerotruncus, and Ruminiclostridium demonstrated negative correlations with CD8+ T cells but positive correlations with CD4+ T cells and MDSC cells in both age groups. Taxon set enrichment analysis revealed 58 significantly enriched host gene targets in the young cluster compared to only 11 in the aged cluster. These findings highlight the relationship between ISV treatment efficacy and gut microbiome composition, suggesting that interventions such as diet modification, probiotics, or fecal microbiota transplantation may hold potential as therapeutic strategies to enhance immune responses against solid tumors.

Abstract Recent efforts in designing nanomaterials to deliver potential therapeutics to the targeted site are overwhelming and palpable. Engineering nanomaterials to deliver biological molecules to exert desirable physiological changes, with minimized side effects and optimal dose, has revolutionized the next-generation therapy for several diseases. The rapid progress of nucleic acids as biopharmaceutics is going to alter the traditional pharmaceutics practices in modern medicine. However, enzymatic instability, large size, dense negative charge (hydrophilic for cell uptake), and unintentional adverse biological responses—such as prolongation of the blood coagulation and immune system activation—hamper the potential use of nucleic acids for therapeutic purposes. Moreover, the safe delivery of nucleic acids into the clinical setting is an uphill task, and several efforts are being put forward to deliver them to targeted cells. Advances in Metal-based NanoParticles (MNPs) are drawing attention due to the unique properties offered by them for drug delivery, such as large surface-area-to-volume ratio for surface modification, increased therapeutic index of drugs through site-specific delivery, increased stability, enhanced half-life of the drug in circulation, and efficient biodistribution to the desired targeted site. Here, the potential of nanoparticles delivery systems for the delivery of nucleic acids, specially MNPs, and their ability and advantages over other nano delivery systems are reviewed. Graphical Abstract

Purpose: The recent Omicron (B.1.1.529) variant poses a significant threat to global health. This variant has spread worldwide, and several sublineages have rapidly emerged. Study tried to analyze the microevolution of this variant. Methods: We studied the molecular phylogenetics, divergence, geographical distributions, frequencies, risk mutations for antibody affinity, and mutational landscape for Omicron sublineages using in silico analysis and statistical models. The risk mutation of spike for nAb affinity was analyzed and illustrated by statistical plots. Finally, the mutational properties of the spike mutations and their stability were predicted and demonstrated. Results: First, we studied the microevolutionary Omicron sublineages using molecular phylogenetics. Simultaneously, we revealed divergence events of the Omicron sublineages and observed the lowest minimum divergence of 51 in clade 21K and the highest maximum divergence of 90 in clade 21L. We have demonstrated cluster analyses, geographical distributions, frequencies of Omicron and its sublineages. Finally, we evaluated the mutational landscape of the Omicron sublineages. In this mutational study, we performed a genome-wide analysis of general mutations, mutations in the non-spike genome, and spike mutations of Omicron sublineages. The risk mutation of S-glycoprotein for nAb affinity has been analyzed for Omicron sublineages. Here, we found that some sublineages have all four significant highly destabilizing mutations. Such sublineages are BA.1 (G446S, E484A, T95I, and D614G), BA.2 (H655Y, Q493R, G493S, and D614G), BA.4 (N501Y, Y505H, N969K, and D614G), and BA.2.75 (Q454H, T547K, N764K, D614G and G446S). Finally, from the mutation stability prediction through ΔΔG, we observed that BA.1 and BA.4 had two destabilizing and two stabilizing mutations. Similarly, BA.2, BA.5, and BA.2.12.1 have one destabilizing and three stabilizing mutations. However, all four mutations in BA.2.75 are stabilizing mutations. Conclusions: Our molecular phylogenetic studies provided a deeper understanding of the microevolution of sublineages and the creation of Omicron. Similarly, this study might help scientists develop pan-coronavirus vaccines that consider their mutational properties.

Introduction: The ultimate aim of blood transfusion services is to give recipients whole blood and blood components that are secure, efficient, and potent. Control, assurance, and audit of quality are the foundational elements of quality. Product standards are developed and accurately met through the process of quality control. Method: In this study, samples of 2.3% PRBCs (50/2155), 9.3% platelet concentrate (42/451), and 3.6% of total whole blood collection (48/1,321) were prepared and tested for haematological parameters of quality control for the period from 1 January 2022 to 31 December 2022. Parameters for 8 samples of platelet concentrate available on day 5, were compared for day 0 and day 5. Result: Haematological metrics for whole blood, PRBCs, and platelet concentrate underwent quality examination. 50/2121, or 2.3% of the total whole blood collection, was used as a sample for the analysis of haematological parameters. Volume and hematocrit tests were performed on a total of 55 out of 2335 (2.3%) units. With a range of 344–365 mL, the average capacity was 358 mL. With a range of 35.1-48.0%, the mean hematocrit was 42.2%. Between 271 to 389 mL, the mean capacity was 311 mL. The range of the mean hematocrit was 57.3 to 81.9%. There was slight decrease in volume, platelet count and WBC count of platelet concentrates on day 5 as compared to day 0. Conclusion: For effective and safe blood transfusion services, continuous quality improvement is crucial. As a result, attention should be taken to apply consistent criteria for quality assessment, and objective analysis should be used on a regular basis to verify that consistent values are being followed.

Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.

Abstract Fault detection and classification is a key challenge for the protection of High Voltage DC (HVDC) transmission lines. In this paper, the Teager–Kaiser Energy Operator (TKEO) algorithm associated with a decision tree-based fault classifier is proposed to detect and classify various DC faults. The Change Identification Filter is applied to the average and differential current components, to detect the first instant of fault occurrence (above threshold) and register a Change Identified Point (CIP). Further, if a CIP is registered for a positive or negative line, only three samples of currents (i.e., CIP and each side of CIP) are sent to the proposed TKEO algorithm, which produces their respective 8 indices through which the, fault can be detected along with its classification. The new approach enables quicker detection allowing utility grids to be restored as soon as possible. This novel approach also reduces computing complexity and the time required to identify faults with classification. The importance and accuracy of the proposed scheme are also thoroughly tested and compared with other methods for various faults on HVDC transmission lines.

Objective: Osteoporosis is regarded as a silent disorder affecting bone slowly, leading to an increased risk of fractures. Lately, selenium has been found to be associated with the acquisition and maintenance of bone health by affecting the bone remodeling process. However, the mechanism of action of selenium on bone is poorly understood. Here, the protective effects of sodium selenite on the differentiation process of osteoblasts as well as under oxidative stress-induced conditions were evaluated.Materials and Methods: MC3T3-E1 cells, were treated with a various doses (0, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2, 6.4 ug/ml) of sodium selenite. Cell viability and cytotoxicity were observed by MTT and LDH assay. The osteogenic activity and expression level of osteogenic markers were confirmed through ALP activity, real-time RT-PCR and sirius red staining. Role of sodium selenite and involvement of WNT signaling was assessed by Axin-2 reporter assay and western blotting.Results: It was observed that the sodium selenite could promote the ALP activity and collagen synthesis in pre-osteoblasts. Moreover, sodium selenite increased the mRNA expression levels of osteogenic transcriptional factors, such as runt-related transcription factor 2 (Runx2) and osterix (OSX). In addition, the terminal differentiation markers, such as osteocalcin (OCN), and collagen 1α (Col1α), were also increased. Treatment of sodium selenite recused the H2O2-induced inhibition of osteoblastic differentiation of pre-osteoblasts cells. Furthermore, sodium selenite restored the H2O2 repressed β-catenin stability and axin-2 reporter activity in MC3T3-E1 cells implicating involvement of WNT signaling pathway.Conclusion: It may be concluded that selenite can stimulate bone formation and rescue the oxidative repression of osteogenesis by activating WNT signaling pathway and may act as a potential therapeutic intervention for osteoporosis.

Abstract Fibrous-type filters are used to capture dust particles in mining and other occupations where personnel are exposed for prolonged periods. Dust cleansing devices including flooded-bed dust scrubbers use these mesh-type multi-layered filters. These filters trap dust particles efficiently on their surface and inside their mesh. However, their continued operation leads to dust build-up and clogging. This results in increased resistance of the filter and lowered airflow rate through the scrubber. This could potentially enhance the exposure of the miners. A non-clogging self-cleaning impingement screen type dust filter was designed by the authors for use in mining and industrial dust cleansing applications. The filter guides dirt-laden air through rapidly turning paths which forces it to shed heavier particles. The particles impact one of the impermeable solid metallic filter surfaces and are removed from the airstream. A full cone water spray installed upstream prevents any surface build-up of dust. This paper summaried the computer models generated to show the filter operations and laboratory experiments including optical particle counting to establish the cleaning efficiency.

During the second wave of COVID-19, a number of patients requiring invasive or noninvasive pressure support ventilation rose significantly. The cases of pneumomediastinum (PM), pneumothorax (PTX), and subcutaneous emphysema (SCE) were also reported, largely attributed to barotrauma with observation of some spontaneous cases. Here, we present seven moderate-to-severe COVID-19 cases with variable severity developing PM with or without PTX and SCE during the course of hospitalization. Five received noninvasive ventilation, of whom two required invasive mechanical ventilation. The remaining two patients received oxygen therapy alone. Two patients required insertion of intercostal chest drainage tubes for pneumothoraces. Appropriate medical management was given to all patients. Three patients improved and were discharged from the hospital, while four expired. The case series highlights need of early diagnosis, constant monitoring, and judicious use of pressure support ventilation to prevent air leak complications in COVID-19 patients in order to improve their prognostic outcomes.

Abstract Morphological profiling is an omics-based approach for predicting intracellular targets of chemical compounds in which the dose-dependent morphological changes induced by the compound are systematically compared to the morphological changes in gene-deleted cells. In this study, we developed a reliable high-throughput (HT) platform for yeast morphological profiling using drug-hypersensitive strains to minimize compound use, HT microscopy to speed up data generation and analysis, and a generalized linear model to predict targets with high reliability. We first conducted a proof-of-concept study using six compounds with known targets: bortezomib, hydroxyurea, methyl methanesulfonate, benomyl, tunicamycin, and echinocandin B. Then we applied our platform to predict the mechanism of action of a novel diferulate-derived compound, poacidiene. Morphological profiling of poacidiene implied that it affects the DNA damage response, which genetic analysis confirmed. Furthermore, we found that poacidiene inhibits the growth of phytopathogenic fungi, implying applications as an effective antifungal agent. Thus, our platform is a new whole-cell target prediction tool for drug discovery.

Segmental pulmonary arterial hypertension occurs when the right and left pulmonary arteries are nonconfluent and receive blood supply from different sources. High blood pressure confined to limited lung segments may accelerate progression of pulmonary vascular resistance. Calculation of segmental vascular resistance and assessment of operability in such situations are done after integrating catheter hemodynamics, magnetic resonance imaging techniques, or perfusion scintigraphy. When an isolated pulmonary artery perfused by a restrictive ipsilateral arterial duct is associated with a large nonrestrictive contralateral arterial duct connected to the other pulmonary artery, leading to unilateral pulmonary arterial hypertension and features of high vascular resistance, it offers unique challenges to decision-making.

IntroductionAnti-CD40 agonistic antibody (αCD40), an activator of dendritic cells (DC) can enhance antigen presentation and activate cytotoxic T-cells against poorly immunogenic tumors. However, cancer immunotherapy trials also suggest that αCD40 is only moderately effective in patients, falling short of achieving clinical success. Identifying factors that decrease αCD40 immune-stimulating effects can aid the translation of this agent to clinical reality.Method/ResultsHere, we reveal that β-adrenergic signaling on DCs directly interferes with αCD40 efficacy in immunologically cold head and neck tumor model. We discovered that β-2 adrenergic receptor (β2AR) activation rewires CD40 signaling in DCs by directly inhibiting the phosphorylation of IκBα and indirectly by upregulating levels of phosphorylated-cAMP response element-binding protein (pCREB). Importantly, the addition of propranolol, a pan β-Blocker reprograms the CD40 pathways, inducing superior tumor regressions, increased infiltration of cytotoxic T-cells, and a reduced burden of regulatory T-cells in tumors compared to monotherapy.ConclusionOur study highlights an important mechanistic link between stress-induced β2AR signaling and reduced αCD40 efficacy in cold tumors, providing a new combinatorial approach to improve clinical outcomes in patients.

Therapy-related leukemias(t-leukemia) are late complications arising from chemotherapy and radiotherapy. t-leukemia have a poor prognosis and are more difficult to treat compared to de novo leukemias. The authors present three cases of t-leukemia seen in our hospital in a three year period and discuss new updates concerning the treatment of t-leukemia.

Advances in understanding miRNAs as endogenous posttranscriptional regulatory units have projected them as novel therapeutics for several untreatable diseases. miRNAs are endogenous non-coding small single-stranded RNA molecules (20–24 nucleotides) with specific gene regulatory functions like repression of mRNA translation by degrading mRNAs. Emerging evidence suggests the role of miRNAs in various stages of bone growth and development. Undoubtedly, due to their critical role in bone remodeling, miRNAs might be projected as a novel approach to treating bone-related diseases. However, the instability associated with miRNAs in their complex environment, such as degradation by nucleases, is a concern. Thus, recent attention is being paid to maintaining the miRNAs' safety and efficacy in the cells. Various efficient delivery systems and chemical modifications of miRNAs are being developed to make them a potential therapeutic option for bone diseases. Here, we have tried to recapitulate the recent advances in the role of miRNAs in bone disease, along with the potential delivery systems for their efficient delivery to the cells.

A series of 3-substituted-spiro-(1,3-dithiolan-2,2′-thiazolidin)-4-ones(2) designed as antimicrobial agents and have been synthesized by the reaction between [1,3]dithiolan-2-ylidene-(substituted-phenyl)amine (1) and mercaptoacetic acid. The reaction between substituted anilines, sodium hydroxide and carbon disulfide followed by the reaction of 1, 2-dichloroethane gave quantitatively and analytically pure compound (1). The structure of synthesized compound (1) and (2) is based on spectral (IR, 1H NMR, 13C NMR) as well elemental analysis. These compounds have been screened for their antimicrobial and antitubercular activities. Some of them have showed significant inhibition on bacterial and fungal growth. Few of them showed moderate antitubercular profile. Docking studies of the some novel compounds were performed and results showed that these compounds have good binding energy and have better binding affinity towards the active pocket, thus they may be considered as good inhibitors for selective proteins. Furthermore, computational studies of some derivatives were also performed using Gaussian suite of program.

Recently, several emerging variants of SARS-CoV-2 have originated from the Wuhan strain and spread throughout the globe within one and a half years. One mutation, D614G, is very prominent in all VOI and VOC in SARS-CoV-2. This mutation might help to increase the viral fitness in all emerging variants where the mutation is present. With the help of this mutation (D614G), the SARS-CoV-2 variants have gained viral fitness to enhance viral replication and increase transmission. This paper attempts to answer the question of whether the mutation (D614G) occurs due to positive selection or not.

Relevance . With growing economy and flourishing construction industries the comorbidities among construction workers are also raised. They are exposed to various dust, fumes, noxious gases and vapours making them susceptible to chronic airway diseases like Chronic Obstructive Lung Disease. The aim of the study was to evaluate the respiratory health status of construction workers in an unorganised sector. Materials and Methods . The data collected from National Capital of Delhi region in an unorganised sector of construction workers by using a Saint George Respiratory Questionnaire by the Institute of Occupational Health and Environmental research, Basaidarapur, Delhi, India. All the participant response was noted and the answers were evaluated to see respiratory health status of workers. Total 200 workers were evaluated. Total 182 males and 18 female participated in the study. Results and Discussion . 25% of workers reported poor health at the time of the survey, while only 4% of workers considered their health to be very good. Among the main complaints were indicated: cough, sputum production, shortness of breath, chest infections, attacks of wheezing. The overall mean of Saint George Respiratory Questionnaire core was 33.55. It increases with the working period in the construction field with 21.6% for 10years and 49.1 for 30years experienced workers, while workers with 11 to 20 years of experience, the score was 28.4. The Saint George Respiratory Questionnaire score was 35.1 in 21-30 years of experienced construction workers. Conclusion . As a result of the study, construction workers are found to be at high risk of various respiratory diseases and related disabilities. Participants in this study did not receive any treatment for respiratory problems at any clinic. This means the importance of occupational health education and the use of personal protective equipment and safe working conditions for construction workers.

Abstract The authors have proposed an inverter resistor capacitor (IRC)‐based simple chaotic ring oscillator with dual feedback for the generation of the chaotic waveform. The proposed chaotic system uses three coupled autonomous first‐order differential equations and it can be electrically demonstrated using the complementary metal oxide semiconductor (CMOS) inverters with few passive RC elements for the generation of the high‐frequency strange attractor. The basic dynamical characteristics and multistability property with complex bifurcation pattern in a wide range of parameters are well observed through theoretical as well as numerical simulation analysis using scaled inverse tangent function. In addition, a simple IRC chaotic model design is investigated using 0.18μm MOS transistor parameters with grounded capacitors and an equivalent CMOS‐based scaled inverse tangent function. Moreover, the Cadence post layout simulation gives useful information about the circuit sustainability for IC design with high frequency (MHz), low power dissipation (940 μW) and small chip area (826.3 μm2).

Introduction: Rising morbidty resulting from Obstructive Sleep Apnoea (OSA) is an emerging public health concern. The estimated prevalence of OSA in India has been investigated. STOP-Bang and Epworth Sleepiness Scale (ESS) have proven beneficial in identifying sleep breathing disorder. Validity of these questionnaire has been verified against polysomnography in many studies. Aim: To assess the predictive ability of STOP-Bang questionnaire and ESS in identifying OSA and comparing their efficacy with polysomnography. Materials and Methods: The cross-sectional study was conducted in the Department of Respiratory Medicine, Government Medical College, Kota, Rajasthan, India, from January 2020 to June 2021, among 100 patients with symptoms of OSA. The STOP-Bang questionnaires were administered to the patients, and scoring was done, followed by overnight attended polysomnography. The normality of data was tested by Shapiro Wilk’s test. The values obtained were statistically analysed and to compare the parameters between groups and with in groups for normal data parametric test One-way Analysis of Variance (ANOVA) followed by Tukey’s HSD test, for intragroup Paired t-test. Results: Mean age of the study population was 49.46±6.523 years, 79 were males and 21 females. Total, 79% of the subjects were males, and 21% of the study subjects were females. Among the 100, 65% had OSA as per polysomnography. STOP-Bang questionnaire had a higher sensitivity as compared to ESS in predicting OSA (75.38% for STOP-Bang and 72.31% for ESS). Conversely, the specificity of ESS (82.8%) was found to be greater than STOP-Bang (45.71%). Similar results were obtained for positive predictive value, in which ESS scored 88.6% while STOP-Bang scored 50%. For negative predictive values, ESS again scored higher (65%) than STOP-Bang (61.7%). Similarly, the Likelihood Ratio for a positive result (LR+) of ESS was greater than STOP-Bang (4.2 and 1.3 respectively). The STOP-Bang questionnaire, however, had higher Likelihood Ratio for a negative test (LR-) as compared to ESS (0.5 and 0.3 respectively). Conclusion: Polysomnography is the gold standard to diagnose OSA. For screening OSA, patients with symptoms of sleep disordered breathing, this study found that STOP-Bang questionnaire is better in identifying OSA as compared to ESS.

Circular RNAs (circRNAs), an emerging family member of RNAs, have gained importance in research due to their new functional roles in cellular physiology and disease progression. circRNAs are usually available in a wide range of cells and have shown tissue-specific expression as well as developmental specific expression. circRNAs are characterized by structural stability, conservation, and high abundance in the cell. In this review, we discuss the different models of biogenesis. The properties of circRNAs such as localization, structure and conserved pattern, stability, and expression specificity are also been illustrated. Furthermore, we discuss the biological functions of circRNAs such as microRNA (miRNA) sponging, cell cycle regulation, cell-to-cell communication, transcription regulation, translational regulation, disease diagnosis, and therapeutic potential. Finally, we discuss the recent research progress and future perspective of circRNAs. This review provides an understanding of potential diagnostic markers and the therapeutic potential of circRNAs, which are emerging daily.

Abstract We describe a novel algorithm for information recovery from DNA sequences by using a digital filter. This work proposes a three-part algorithm to decide the k-mer or q-gram word density. Employing a finite impulse response digital filter, one can calculate the sequence's k-mer or q-gram word density. Further principal component analysis is used on word density distribution to analyze the dissimilarity between sequences. A dissimilarity matrix is thus formed and shows the appearance of cluster formation. This cluster formation is constructed based on the alignment-free sequence method. Furthermore, the clusters are used to build phylogenetic relations. The cluster algorithm is in good agreement with alignment-based algorithms. The present algorithm is simple and requires less time for computation than other currently available algorithms. We tested the algorithm using beta hemoglobin coding sequences (HBB) of 10 different species and 18 primate mitochondria genome (mtDNA) sequences.

The rapid spread of the SARS-CoV-2 virus and its variants has created a catastrophic impact worldwide. Several variants have emerged, including B.1.351 (Beta), B.1.1.28/triple mutant (P.1), B.1.1.7 (Alpha), and B.1.429 (Epsilon). We performed comparative and comprehensive antigenicity mapping of the total S-glycoprotein using the Wuhan strain and the other variants and identified 9-mer, 15-mer, and 20-mer CTL epitopes through in silico analysis. The study found that 9-mer CTL epitope regions in the B.1.1.7 variant had the highest antigenicity and an average of the three epitope types. Cluster analysis of the 9-mer CTL epitopes depicted one significant cluster at the 70% level with two nodes (KGFNCYFPL and EGFNCYFPL). The phage-displayed peptides showed mimic 9-mer CTL epitopes with three clusters. CD spectra analysis showed the same band pattern of S-glycoprotein of Wuhan strain and all variants other than B.1.429. The developed 3D model of the superantigen (SAg)-like regions found an interaction pattern with the human TCR, indicating that the SAg-like component might interact with the TCR beta chain. The present study identified another partial SAg-like region (ANQFNSAIGKI) from the S-glycoprotein. Future research should examine the molecular mechanism of antigen processing for CD8+ T cells, especially all the variants’ antigens of S-glycoprotein.

Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated ‘hot’ targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (>70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model.

This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU.

Background: miRNAs, a class of small endogenous RNAs, are one of the essential biopharmaceuticals which are in commercial spans as next-generation medicine in recent times. Aim of the Review: A snapshot of the current scenario regarding the miRNAs as biopharmaceuticals have been discussed. Key Scientific Concepts of Review: In this work, biopharmaceutical companies working with miRNAs and the current status of preclinical/clinical trials about miRNA therapeutics have been reviewed. Finally, recent updates on the absorption, distribution, metabolism, and excretion (ADME), as well as a delivery system of miRNAs, have been illustrated.

Purpose: Oral cancers are one of the commonly diagnosed tumors worldwide in human and veterinary patients. Most oral cancers are surgically resected; however, obtaining an adequate margin of safety in patients without compromising their quality of life is often challenging. Herein, we investigated the ability of non-invasive focused ultrasound (FUS) to thermally ablate a biopsy confirmed canine oral cancer. Materials and Methods: A male canine patient with a large neurilemmoma (schwannoma) mass on the left maxilla, with evidence of thinning and loss of alveolar bone and pressure necrosis, was treated with FUS ablation instead of the traditional maxillectomy procedure. FUS ablations were performed in three sessions over three weeks. Tumor remission was determined with computed tomography and histopathological examination of the treated site. Additionally, the anti-tumor immune effects of FUS were assessed by flow cytometry analysis of blood and tumor samples. Results: Complete tumor remission was noted at the treated site. Treatment related adverse events were primarily thermal burns of the buccal mucosa, which were managed with periodic hyperbaric oxygen therapy and surgical coverage of the underlying exposed bones with gingival flaps. Enhanced proliferation of adaptive immunity cells (e.g., T-cells) was observed in tumor and blood samples. Conclusion: Our limited investigation in a canine oral cancer patient suggests that FUS may avoid the need for large-scale resection of bony tissues, thus potentially improving quality of life.

Objective: Rspondins (RSPOs) are regarded as the significant modulators of WNT signaling pathway and they are expressed dynamically during developmental stages. Since in osteoarthritis (OA) both cartilage and subchondral bone suffer damages and WNT signaling pathway has a crucial role in their maintenance, the objective of the study was to analyze expression profile of RSPO family and its receptors [leucine-rich repeat-containing G-protein coupled receptors (LGRs)] in OA tissue samples as well as in differentiating chondrocytes and osteoblasts. Material and Methods: In this experimental study, human early and advanced stage of OA tissue samples were analyzed for the morphological changes of articular cartilage by hematoxylin and eosin (H&E) staining, safranin-O staining and lubricin immunostaining. RSPOs and LGRs expression were confirmed by immunohistochemistry. Human primary chondrocytes and human osteoblast cell line, SaOS-2, were cultured in differentiation medium till day 14 and they were analyzed in terms of expression of RSPOs, LGRs and specific marker for chondrogenesis and osteogenesis by western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: Advanced stage OA tissue samples showed increased expression of RSPO1 and LGR6 in a region close to subchondral bone. While RSPO2 and LGR5 expression were seen overlapping in the deep region of articular cartilage. Differentiating chondrocytes demonstrated elevated expression of RSPO2 and LGR5 from day 7 to day 14, whereas, osteoblasts undergoing differentiation showed enhanced expression of RSPO1 and LGR6 from day 2 to day 14. Under tumor necrosis factor alpha (TNFα) stimulatory conditions, RSPO2 and RSPO1 recovered the suppressed expression of inflammatory, chondrogenic and osteogenic markers, respectively. A recovery in the stability of β-catenin was also noticed in both cases. Conclusions: Spatial expression of RSPOs during progression of OA might be dynamically controlled by cartilage and subchondral bone. Interplay amid chondrocytes and osteoblasts, via RSPOs, might provide probable mechanisms for treating inflammatory pathogenic conditions like OA.

Immunotherapy to treat cancer is now an established clinical approach. Immunotherapy can be applied systemically, as done with checkpoint blockade antibodies, but it can also be injected directly into identified tumors, in a strategy of in situ vaccination (ISV). ISV is designed to stimulate a strong local antitumor immune response involving both innate and adaptive immune cells, and through this generate a systemic antitumor immune response against metastatic tumors. A variety of ISVs have been utilized to generate an immunostimulatory tumor microenvironment (TME). These include attenuated microorganisms, recombinant proteins, small molecules, physical disruptors of TME (alternating magnetic and focused ultrasound heating, photothermal therapy, and radiotherapy), and more recently nanoparticles (NPs). NPs are attractive and unique since they can load multiple drugs or other reagents to influence immune and cancer cell functions in the TME, affording a unique opportunity to stimulate antitumor immunity. Here, we describe the NP-ISV therapeutic mechanisms, review chemically synthesized NPs (i.e., liposomes, polymeric, chitosan-based, inorganic NPs, etc.), biologically derived NPs (virus and bacteria-based NPs), and energy-activated NP-ISVs in the context of their use as local ISV. Data suggests that NP-ISVs can enhance outcomes of immunotherapeutic regimens including those utilizing tumor hyperthermia and checkpoint blockade therapies.

FDA approval of anti-CTLA4 in 2011 for melanoma immunotherapy was paradigm shifting and dramatically accelerated cancer immunotherapy research. The investment and effort have been exceptionally large, with a commensurate impressive pace of discovery. Historical and current research has validated the following key points: tumors are recognized by the immune system; tumors develop an immunosuppressive environment which suppresses the antitumor immune response; successful immunotherapy must overcome that tumor-mediated immunosuppression. While cancer immunotherapy research expanded, a parallel effort developing nanoparticles (NP) for cancer diagnosis and therapy also received major investment and expanded. Initially the two efforts appeared to have minimal synergy. Systemically administered nanoparticles are rapidly ingested by phagocytic leukocytes, and therefore nanotechnologists developed strategies to avoid NP ingestion by leukocytes in order to accomplish nanoparticle accumulation in tumors rather than liver and spleen. Recently, nanotechnology and cancer immunotherapy have increasingly merged since phagocytic leukocytes are the key to reversing the local tumor immunosuppression and the tendency of NP to be phagocytosed can be exploited to manipulate phagocytes for immunotherapy. This review focuses on in situ vaccination (ISV), an immunotherapy approach that can utilize direct injection of immunostimulatory reagents, including NPs, into tumors to disrupt the local immunosuppression, stimulate effective immune response against the treated tumor, and most importantly, generate a systemic antitumor immune response to eliminate metastatic tumors. While there are many specific options for using NP for ISV (reviewed further in this special issue), this review focuses on immunology concepts needed to understand and design successful NP ISV approaches.

Inflammation is closely related with the progression of cancer and is an indispensable component that orchestrates the tumor microenvironment. Studies suggest that different mediator and cellular effectors, including cytokines (interleukins, tumor necrosis factor-α [TNF-α], transforming growth factor-β [TGF-β], and granulocyte macrophage colony-stimulating factor [GM-CSF]), chemokines, as well as some transcription factors (nuclear factor κB [NF-κB], signal transducer and activator of transcription 3 [STAT3], hypoxia-inducible factor-1α [HIF1α]), play a crucial role during cancer-related inflammation (CRI). MicroRNAs (miRNAs) are the key components of cellular physiology. They play notable roles during posttranscriptional gene regulation and, thus, might have a potential role in controlling the inflammatory cascade during cancer progression. Taking into consideration the role identified for miRNAs in relation to inflammatory cytokines, we have tried to review their participation in neoplastic progression. Additionally, the involvement of miRNAs with some important transcription factors (NF-κB, STAT3, HIF1α) and proteins (cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [iNOS]) closely associated with inflammation during cancer has also been discussed. A clear insight into the responsibility of miRNAs in cytokine signaling and inflammation related to CRI could project them as new therapeutic molecules, which could lead to improved treatment of CRI in the near future.

Dust generated in mining and tunneling activities is hazardous to health of persons and safety of operations. These projects employ pick-milling machines to extract minerals and rock by mechanical breakage. The machines are equipped with flooded-bed scrubbers that encase dust particles within fine water films as particles encounter a flooded wire-mesh screen. A major disadvantage is that the screen gets clogged when particles become trapped within the wire mesh, reducing airflow through the scrubber and increasing ambient dust concentrations. Thus, the system requires frequent maintenance or replacement. The application of a Vortecone scrubber as an improved alternative to conventional fibrous type scrubbers is investigated. A Vortecone forces dust-laden air and water to follow a complex, rapidly swirling motion. The momentum drives dust particles towards the periphery where they are captured by the water film. The operating characteristics of a reduced-scale physical model of a Vortecone, with its primary axis mounted in the horizontal orientation, was analyzed numerically and experimentally. Computational fluid dynamics (CFD) models depicting the spraying action and multi-phase air/water flows using the volume of fraction (VOF) approach, are presented. Experimental results, utilizing an optical particle counting technique to establish the dust-cleaning capabilities of the model, are also described.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus (CoV), has recently emerged as a significant pathogen for humans and the cause for the recent outbreak of the 2019 novel coronavirus disease (COVID-19) throughout the globe. For developing any preventive measure, an understanding of the zoonotic pattern for this virus is a necessity. We should have a clear knowledge of its reservoir host, its distribution pattern and spreading routes. Information about zoonotic reservoirs and its transmission among them can help to understand the COVID-19 outbreaks. In this article, we discuss about the bats as the zoonotic reservoir of several CoV strains, co-existence of bats and CoV/viruses, the sequence similarity of SARS-CoV-2 with bat SARS-like CoV, the probable source of the origin of SARS-CoV-2 strain and COVID-19 outbreak, intermediate host of CoVs and SARS-CoV-2, human to human transmission and the possibility to maintain the zoonotic barriers. Our knowledge about the zoonotic reservoir of SARS-CoV-2 and its transmission ability may help develop the preventive measures and control for the future outbreak of CoV.

Various random regression models with different order of Legendre polynomials for permanent environmental and genetic effects were constructed to evaluate Murrah buffaloes under field condition. A total of 24,160 test-day (TD) milk yield records of 2,336 buffaloes belonging to six districts of Haryana state from 2014 to 2019 under CHRS Rohtak were considered for estimating the random covariate coefficients using REML algorithm. The R2 and BIC improved up to seventh order of the polynomials but decreased at 8th order. The lowest value of AIC was for 8th order of polynomial. The models with LPs of order 5 and above gave an improved fit of the lactation curve having high R2 value (>98%). However, the number of parameters increased from 13 for LP of order 3 to 73 for LP of order 8 indicating over parameterization of models. Best order of fit was 7th order having highest R2 (99.23%), lowest AIC and lowest BIC value. The lactation curves plotted from the ETDMYs obtained under RRMs using LP5 and LP7 were smoother as compared to the lactation curve obtained from arithmetic mean. The 301 day lactation yield under RRMs using LP of order 7 and 5 averaged 3470.42±2.76 kg and 3460.72±3.10 kg, respectively. The milk yield ranged from 3,456.38 kg in Bhiwani district to 3,480.86 kg in Sonipat district under LP7 model while it ranged from 3,426.35 kg in Jhajjar district to 3,503.95 kg in Bhiwani district under LP5 model. It was observed that less than 50% were common in top 1% of total buffaloes under the two RRMs. The RRM using LP of order 7, which provided more accurate breeding values, must be considered for selection of top ranking/ superior animals for breeding purpose.

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of SARS-CoV-2 are emerging in due course of time with substantial mutations, having the immune escape property. Simultaneously, the vaccination drive against this virus is in progress worldwide. However, vaccine evasion has been noted by some of the newly emerging variants. Our review provides an overview of the emerging variants’ immune escape and vaccine escape ability. We have illustrated a broad view related to viral evolution, variants, and immune escape ability. Subsequently, different immune escape approaches of SARS-CoV-2 have been discussed. Different innate immune escape strategies adopted by the SARS-CoV-2 has been discussed like, IFN-I production dysregulation, cytokines related immune escape, immune escape associated with dendritic cell function and macrophages, natural killer cells and neutrophils related immune escape, PRRs associated immune evasion, and NLRP3 inflammasome associated immune evasion. Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein. Mutations in other locations such as NSP1, NSP3, NSP6, ORF3, and ORF8 have also been discussed. Finally, we have illustrated the emerging variants’ partial vaccine (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) escape ability. This review will help gain in-depth knowledge related to immune escape, antibody escape, and partial vaccine escape ability of the virus and assist in controlling the current pandemic and prepare for the next.

Adrenal myelolipomas are rare benign adrenal tumour composed of mature adipocytes intermixed with myeloid tissue. They are second most common cause after adrenal adenomas and comprise of 6-16% of all the adrenal incidentalomas. They are often asymptomatic and therefore, rarely detected but in recent times due to radiological advancements, these cases are increasingly being detected and therefore, treated. Extra-adrenal myelolipoma are the myelolipomas, detected outside the adrenal gland but occur rarely. Three cases (53 years old male patient, 60 years old male patient and 46 years old female patient) of clinically and radiologically suspected cases of symptomatic adrenal myelolipoma are discussed here. The first case described, presented with right flank pain radiating to back which was suspected as adrenal mass by Computed Tomography (CT) evaluation. The second case presented with right flank pain, haematuria and weight loss which was suspected on Ultrasonography (USG) and Contrast Enhanced Computed Tomography (CECT) as an adrenal mass. The third patient presented with bilateral pedal oedema and suspected adrenal mass was found on USG. All three cases were histopathologically confirmed as adrenal myelolipoma and managed by surgical excision. The uniqueness of the case lies in its early detection due to technological advancements and hence, proper management of the patients.

Pterocarpus marsupium Roxb., a significant deciduous tree species of high medicinal value is depleting fast due to various biotic and abiotic factors and is included in the near threatened species category of IUCN red list. The potential distribution range of P. marsupium for India was modeled for the year 2020 and 2050 under different Representative Concentration Pathways (RCP 2.6, 4.5, 6.0 8.5) scenarios of climate change using Maxent, to study the impact of climate change on its distribution. The study revealed that at present ~3.08% geographical area of India is highly suitable to distribution of P. marsupium and depending upon RCP this may expand upto ~ 3.11-3.53% by 2050. The zone wise analysis for the present climatic conditions predicted prominent presence of high suitable habitat range of P. marsupium in the central zone comprising ~ 1.82% of the total geographical area of India followed by southern and western zones with ~ 0.53% and ~ 0.49% distribution area respectively. The study predicted northward shifting of suitable habitat by 2050 with an increase in suitable area in the range of ~0.6-11%, ~6.4-24.5% and ~20-60% for the central, southern and western zone respectively, but ~26%-53% decrease in the eastern zone. Annual precipitation (Bio_12) was the most significant contributor variable in limiting the distribution of P. marsupium for the present as well as future climatic conditions. The result provides baseline information for identification and prioritization of areas for the conservation and promotion of P. marsupium in India.

The COVID-19 pandemic has created an urgent situation throughout the globe. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability. The DEGs will help understand the disease’s potential underlying molecular mechanisms and genetic characteristics, including the regulatory genes associated with immune response elements and protective immunity. This study aimed to determine the DEGs in mild and severe COVID-19 patients versus healthy controls. The Agilent-085982 Arraystar human lncRNA V5 microarray GEO dataset (GSE164805 dataset) was used for this study. We used statistical tools to identify the DEGs. Our 15 human samples dataset was divided into three groups: mild, severe COVID-19 patients and healthy control volunteers. We compared our result with three other published gene expression studies of COVID-19 patients. Along with significant DEGs, we developed an interactome map, a protein-protein interaction (PPI) pattern, a cluster analysis of the PPI network, and pathway enrichment analysis. We also performed the same analyses with the top-ranked genes from the three other COVID-19 gene expression studies. We also identified differentially expressed lncRNA genes and constructed protein-coding DEG-lncRNA co-expression networks. We attempted to identify the regulatory genes related to immune response elements and protective immunity. We prioritized the most significant 29 protein-coding DEGs. Our analyses showed that several DEGs were involved in forming interactome maps, PPI networks, and cluster formation, similar to the results obtained using data from the protein-coding genes from other investigations. Interestingly we found six lncRNAs (TALAM1, DLEU2, and UICLM CASC18, SNHG20, and GNAS) involved in the protein-coding DEG-lncRNA network; which might be served as potential biomarkers for COVID-19 patients. We also identified three regulatory genes from our study and 44 regulatory genes from the other investigations related to immune response elements and protective immunity. We were able to map the regulatory genes associated with immune elements and identify the virogenomic responses involved in protective immunity against SARS-CoV-2 infection during COVID-19 development.

SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.

Pattern recognition plays a critical role in integrative bioinformatics to determine the structural patterns of proteins of viruses such as SARS-CoV-2. This study identifies the pattern of SARS-CoV-2 proteins to depict the structure–function relationships of the protein alphabets of SARS-CoV-2 and COVID-19. The assembly enumeration algorithm, Anisotropic Network Model, Gaussian Network Model, Markovian Stochastic Model, and image comparison protein-like alphabets were used. The distance score was the lowest with 22 for “I” and highest with 40 for “9”. For post-processing and decision, two protein alphabets “C” (PDB ID: 6XC3) and “S” (PDB ID: 7OYG) were evaluated to understand the structural, functional, and evolutionary relationships, and we found uniqueness in the functionality of proteins. Here, models were constructed using “SARS-CoV-2 proteins” (12 numbers) and “non-SARS-CoV-2 proteins” (14 numbers) to create two words, “SARS-CoV-2” and “COVID-19”. Similarly, we developed two slogans: “Vaccinate the world against COVID-19” and “Say no to SARS-CoV-2”, which were made with the proteins structure. It might generate vaccine-related interest to broad reader categories. Finally, the evolutionary process appears to enhance the protein structure smoothly to provide suitable functionality shaped by natural selection.

ABSTRACT The recent emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant concern for public health worldwide. New variants have been classified either as variants of concern (VOCs) or variants of interest (VOIs) by the CDC (USA) and WHO. The VOCs include lineages such as B.1.1.7 (20I/501Y.V1 variant), P.1 (20J/501Y.V3 variant), B.1.351 (20H/501Y.V2 variant), and B.1.617.2. In contrast, the VOI category includes B.1.525, B.1.526, P.2, and B.1.427/B.1.429. The WHO provided the alert for last two variants (P.2 and B.1.427/B.1.429) and labeled them for further monitoring. As per the WHO, these variants can be reclassified due to their status at a particular time. At the same time, the CDC (USA) has marked these two variants as VOIs up through today. This article analyzes the evolutionary patterns of all these emerging variants, as well as their geographical distributions and transmission patterns, including the circulating frequency, entropy diversity, and mutational event diversity throughout the genomes of all SARS-CoV-2 lineages. The transmission pattern was observed highest in the B.1.1.7 lineage. Our frequency evaluation found that this lineage achieved 100% frequency in early October 2020. We also critically evaluated the above emerging variants mutational landscape and significant spike protein mutations (E484K, K417T/N, N501Y, and D614G) impacting public health. Finally, the effectiveness of vaccines against newly SARS-CoV-2 variants was also analyzed. IMPORTANCE Irrespective of the aggressive vaccination drive, the newly emerging multiple SARS-CoV-2 variants are causing havoc in several countries. As per the CDC (USA) and WHO, the VOCs include the B.1.1.7, P.1, B.1.351, and B.1.617.2 lineages, while the VOIs include the B.1.525, B.1.526, P.2, and B.1.427/B.1.429 lineages. This study analyzed the evolutionary patterns, geographical distributions and transmission patterns, circulating frequency, entropy diversity, and mutational event diversity throughout the genome of significant SARS-CoV-2 lineages. A higher transmission pattern was observed for the B.1.1.7 variant. The study also evaluated the mutational landscape and important spike protein mutations (E484K, K417T/N, N501Y, and D614G) of all of the above variants. Finally, a survey was performed on the efficacy of vaccines against these variants from the previously published literature. The results presented in this article will help design future countrywide pandemic planning strategies for the emerging variants, next-generation vaccine development using alternative wild-type antigens and significant viral antigens, and immediate planning for ongoing vaccination programs worldwide.