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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease where standard-of-care chemotherapeutic drugs have limited efficacy due to the development of drug resistance and poor drug delivery caused by a highly desmoplastic tumor microenvironment. Combining multiple drugs in a tumor-targeting carrier would be a favorable approach to overcome these limitations. Hence, a tumor-targeted peptide (TTP) conjugated amphiphilic tri-block copolymer was developed to make targeted polymer nanoparticles (TTP-PNPs) serving as a vehicle for carrying gemcitabine (Gem), paclitaxel (PTX), and their combination (Gem + PTX). The TTP-PNPs in the form of empty polymer (P), single drug-loaded [P(Gem) and P(PTX)], and dual drug-loaded [P(Gem + PTX)] polymer nanoformulations exhibited stable and homogenous spherical shapes with 110–160 nm size. These nanoformulations demonstrated excellent stability under in vitro physiological conditions and led to an efficient release of the drugs in the presence of reduced glutathione (GSH). The efficacy of these nanoparticles was thoroughly evaluated in vitro and in vivo, demonstrating a notable capacity to selectively target and restrict PDAC cells (PANC-1 and KPC) growth. The cellular uptake and biodistribution study showed a significantly higher tumor-targeting ability of TTP-PNPs than PNPs without TTP. Notably, P(Gem + PTX) exhibited the lowest IC50 compared to all other controls and showed heightened synergistic effects in both cell lines. Furthermore, P(Gem + PTX) showed a significantly better tumor reduction and median overall survival in mouse models than single drug-loaded TTP-PNPs or a combination of free drugs (Gem + PTX). In summary, our TTP-PNP system shows great promise as a novel platform for delivering Gem + PTX specifically to pancreatic cancer (PC), maximizing the therapeutic benefits with lower concentrations of the drugs and potentially reducing toxic side effects.

Background: Tianeptine is an antidepressant that acts as an agonist to the mu-opioid receptor and enhances serotonin reuptake. Tianeptine has been legally sold as an antidepressant in some countries but is not approved for any medical use by the U.S. Food and Drug Administration (FDA). Tianeptine is not a federally controlled substance, but became a schedule II substance in Tennessee on July 1, 2022. This publication aims to describe the prevalence of tianeptine-involved emergency department visits, fatal overdoses, and substance seizures in Tennessee from 2021 to 2023. Methods: We conducted a study to examine the prevalence of tianeptine-involved emergency department visits and fatal overdoses in Tennessee using data for 2021 to 2023 from the Tennessee Electronic Surveillance System for the Early Notification of Community based Epidemics (ESSENCE) database and the Tennessee State Unintentional Drug Overdose Reporting System (SUDORS). Substance seizure data from National Forensic Laboratory Information System (NFLIS) are included. Results: Our search of ESSENCE, SUDORS, and NFLIS yielded 50 tianeptine-involved emergency department visits, 6 tianeptine-involved fatal overdoses, and 19 tianeptine substance seizures respectively. Demographic information is provided for the emergency department visits and tianeptine-involved fatal overdoses. Discharge diagnosis and clinical symptomology information are provided for the emergency department visits. Conclusion: Emergency department visits and fatal overdoses involving tianeptine have occurred in Tennessee despite tianeptine becoming a schedule II substance. Among emergency department visits, tianeptine use is most commonly associated with gastrointestinal and psychological symptoms. All fatal cases where tianeptine was detected involved other substances, suggesting tianeptine plays a role in polysubstance use.

Summary: Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in patients receiving mechanical ventilation in India. Surveillance of VAP is essential to implement data-based preventive measures. Implementation of ventilator-associated events (VAE) criteria for surveillance has major constraints for low resource settings, which can lead to significant underreporting. Surveillance of VAP using common protocols in a large network of hospitals would give meaningful estimates of the burden of VAP in low resource settings. This study leverages a previously established healthcare-associated infections (HAI) surveillance network to develop and test a modified VAP definition adjusted for Indian settings. Methods: In this observational pilot study, thirteen hospitals from the existing HAI surveillance network were selected for developing and testing a modified VAP definition between February 2021 and April 2023. The criteria used for diagnosing VAP were adapted from the CDC’s Pediatric VAP definition and modified to cater to the needs of Indian hospitals. Designated nurses recorded each VAP event in a case report form (CRF) and also collected denominator data. The data was entered into an indigenously developed database for validation and analysis. At the time of data analysis, a questionnaire was sent to sites to get feedback on the performance of the modified VAP definitions. Findings: Out of 133,445 patient days and 40,533 ventilator days, 261 VAP events were recorded, with an overall VAP rate of 6.4 per 1000 ventilator days and a device utilization ratio (DUR) of 0.3. A total of 344 organisms were reported from the VAP events. Of these, Acinetobacter spp (29.6%, 102) was the most frequent, followed by Klebsiella spp (26.7%, 92). Isolates of Acinetobacter spp (98%) and Enterobacterales (85.5%) showed very high resistance against Carbapenem. Colistin resistance was observed in 6% of Enterobacterales and 3.2% of Acinetobacter spp. Interpretation: Data from this pilot study needs to validated in the larger Indian HAI surveillance network so that it can help in wider implementation of this protocol in order to assess its applicability p VAP across India. Funding: This work was supported by a grant received from the Indian Council of Medical Research (code I-1203).

Catalysis field wherein a tiny organic molecule like l-proline is an efficient and selectively catalyzed organic reaction. Catalyst-supported organic synthesis is confirmed to be involved in the fast synthesis of novel compounds with selectivity and enhanced biological activities. l-proline catalyzed reactions are valuable tools for the making of different heterocycles, acyclic, and carbocyclic scaffolds that signify the main framework of most of the bio-active compounds. A few decades ago, novel tools for the manufacturing of bio-active molecules had a huge impact on organic chemistry. Subsequently, the synthesis of biologically important heterocycles through a synthetically proficient and environmentally benign route is the important purpose of modern synthetic chemistry. In this review, we discuss only l-proline catalyzed organic reactions (including condensation, addition, asymmetric, multi-components, and other modular reactions) for the sustainable synthesis of biologically promising heterocycles in a single trencher that may provide as a piece of reliable literature for further research in this field.

The seasonal reversal of ocean circulation associated with seasonal change in the direction of prevailing winds and the occurrence of several anomalous events in the Eastern Equatorial Indian Ocean (EEIO) make this region dynamic and complex in terms of its biogeochemical characteristics. Two multidisciplinary cruises were conducted to measure nutrients and associated physicochemical parameters across the water column (up to 1000 m) of the EEIO during boreal summer and winter monsoons to understand the distribution of nutrients and their spatio-temporal variability from a biogeochemical perspective. The seasonality in the thermohaline structure of the region is indistinct except for surface salinity drop during summer monsoon due to more precipitation on-site and in adjoining areas. Low concentrations of chlorophyll at the surface and in the deep chlorophyll maxima represent the oligotrophic nature of this region. Surface water was found nutrient-depleted (0.03–0.4 µM Nitrate, 0.02–0.13 µM Phosphate). The maxima of vertical profiles of nitrate and phosphate were recorded at a shallower depth (150–200 m) when compared to its maxima in usual oceanic conditions, but a silicate maximum was recorded in deeper water. In the surface and upper mixed layer paucity of nutrients resulted in low N:P and N:Si ratios. Therefore, nitrogen limitation is evident. The overall ratio of N:P yielded a mean value of 15.33 and matched with the representative literature value for the Indian Ocean. The minimum oxygen values (

Abstract:: Oxygenated polyunsaturated fatty acids (oxylipins) are important mediators of inflammation ranging from pro- to anti-inflammatory actions. Research investigating differences in the oxylipin profile of dairy cows suffering from different degrees of systemic inflammation in the early postpartum period is lacking and can help advance knowledge on potential mechanisms leading to excessive inflammation. The objective of this preliminary study was to evaluate the plasma oxylipin profile of cows classified in 1 of 4 systemic inflammation categories based on plasma haptoglobin (Hp) concentrations assessed on days in milk (DIM) 1, 2, 3, 4, 5, and 7, in addition to the presence or absence of metritis within 10 DIM, and of cows without any clinical diseases within 21 DIM. Groups were classified as follows: (1) cows with a peak Hp concentration ≤3 DIM (EarlyHp) and diagnosed with metritis; (2) cows with a peak Hp concentration 3 < DIM ≤7 (LateHp) and diagnosed with metritis; (3) cows suffering from persistently elevated Hp concentrations assessed on DIM 4 and 7 while remaining apparently healthy during the first 21 DIM (PersistentHp); and (4) apparently healthy cows not suffering from persistently elevated Hp concentrations (LowHp). Six cows from each category were randomly selected from a plasma bank of a parent cohort study including 380 multiparous cows. Plasma samples on DIM 1 and 2, 3 and 4, and 5 and 7 were proportionally pooled to create 3 samples per cow for lipidomic analysis (i.e., pool 1 = DIM 1 and 2; pool 2 = DIM 3 and 4; pool 3: DIM 5 and 7). Statistical analyses were performed using SAS v9.4 (SAS Institute Inc.) and least squares means adjusted for multiple comparisons using the Tukey-Kramer test. Comparisons for EarlyHp and LateHp were only performed on pooled samples from DIM 1 and 2 (i.e., before metritis diagnosis). EarlyHp cows had decreased concentrations of 9(S)-HOTrE compared with LowHp cows of DIM 1–2 pooled samples. LateHp cows had decreased concentrations of 9(10)-DiHOME compared with LowHp cows. Next, we sought to investigate whether cows classified as PersistentHp had time-dependent differences in oxylipin profile versus LowHp cows. PersistentHp cows had decreased concentrations of 19(R)-HETE compared with LowHp cows in a time-dependent manner (only in pooled samples from DIM 5 and 7). Our results identified oxylipins of interest that warrant further investigation to elucidate their in vitro and in vivo functions in the postpartum inflammatory process of dairy cows.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Summary: Orofacial clefts (OFCs) are among the most common human congenital birth defects. Previous multiethnic studies have identified dozens of associated loci for both cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP). Although several nearby genes have been highlighted, the “casual” variants are largely unknown. Here, we developed DeepFace, a convolutional neural network model, to assess the functional impact of variants by SNP activity difference (SAD) scores. The DeepFace model is trained with 204 epigenomic assays from crucial human embryonic craniofacial developmental stages of post-conception week (pcw) 4 to pcw 10. The Pearson correlation coefficient between the predicted and actual values for 12 epigenetic features achieved a median range of 0.50–0.83. Specifically, our model revealed that SNPs significantly associated with OFCs tended to exhibit higher SAD scores across various variant categories compared to less related groups, indicating a context-specific impact of OFC-related SNPs. Notably, we identified six SNPs with a significant linear relationship to SAD scores throughout developmental progression, suggesting that these SNPs could play a temporal regulatory role. Furthermore, our cell-type specificity analysis pinpointed the trophoblast cell as having the highest enrichment of risk signals associated with OFCs. Overall, DeepFace can harness distal regulatory signals from extensive epigenomic assays, offering new perspectives for prioritizing OFC variants using contextualized functional genomic features. We expect DeepFace to be instrumental in accessing and predicting the regulatory roles of variants associated with OFCs, and the model can be extended to study other complex diseases or traits.

Antimicrobial resistance (AMR) is a global public health concern and needs to be monitored for control. In this study, synanthropic rodents trapped from humans and animal habitats in Puducherry, India, were screened as sentinels for bacterial pathogens of public health importance and antimicrobial resistance spillover. From the trapped rodents and shrews (n = 100) pathogens viz., Staphylococcus sp, E. coli and Salmonella sp were isolated from oropharyngeal and rectal swabs on Mannitol salt, Mac Conkey and Xylose lysine deoxycholate media respectively. The AMR genes in these isolates were screened by PCR. A total of 76, S. aureus and 19, Staphylococcus non aureus were isolated. E. coli was isolated in 89 samples and among the Salmonella sp (n = 59), 16, were S. enteritidis and 29, were S. typhimurium. A total of 46 MRSA isolates with mec A (n = 40) and mec C (n = 6) were detected. Also, 36.84% and 5.3% Staphylococcus non aureus isolates were tested to have mec A and mec C genes. AMR genes encoding ESBL [blaTEM in 21, blaSHV in 45 and blaCTX-M in 11] was tested positive in 77 E. coli isolates. Among, Salmonella isolates 44/45 were screened to have AMR genes [tet in 13, sul3 & sul4 in 20 and qnrA in 11]. Antibiotic sensitivity test confirmed the antimicrobial resistance. Isolation of pathogens of public health importance and demonstration of genetic elements conferring antimicrobial resistance in the synanthropic rodents confirms that they act as reservoirs and appropriate sentinels to monitor AMR spillover in the environment.

Here we present a novel study of Calcium hydroxide and iron-nickel co-doped Calcium hydroxide nanoparticles. Calcium hydroxide (CH) and iron-nickel doped Calcium hydroxide (INCH) nanoparticles (NPs) were synthesized by a simple chemical precipitation method. XRD, FESEM-EDX, and FTIR were used to characterize the structural and morphological characteristics, while UV–Vis spectroscopy was used to study the optical alterations. The average crystallite size is estimated to be 63.75 nm and 66 nm for the CH and INCH nanoparticles, respectively. The FESEM analysis revealed that CHNPs form a hexagonal-like shape, whereas INCH NPs produce highly agglomerated dispersed particles. The UV–Vis spectroscopy revealed that the band gap changes with average crystallite size concurrently.

Adrenaline (AD) is a naturally occurring catecholamine, synthesised in the adrenal medulla to prepare the organisms for a ''fight or flight'' response. Under stressful circumstances, the circulatory catecholamine undergoes auto-oxidation, resulting in the formation of free radicals. Chronic stress results in the depletion of micronutrient stores in the body. Pyridoxine, often known as vitamin B6, is an essential water-soluble vitamin that acts as a coenzyme in many metabolic processes. Therefore, our current investigation has prioritized the regulation of pyridoxine metabolism during the period of chronic stress and the precise role of melatonin, as a natural antioxidant, in preventing the alterations generated by adrenaline in cardiac and hepatic tissues. Adrenaline augmented the oxidative stress indices, leading to an imbalance in the antioxidative state resulting in changes in the levels of certain organ-specific serum markers, modifications in the levels of PL (pyridoxal), PLP (pyridoxal-5-phosphate), and the enzymes responsible for their metabolism and breakdown. The foregoing results were corroborated by the histochemical and histological examinations. Melatonin efficiently counteracted all these harmful changes. Besides, the current study demonstrates that both PLP and melatonin show efficacy in scavenging free radicals, including superoxide anion free radicals and hydroxyl radicals, in the chemical system. However, the in vitro studies demonstrated that when administered together, melatonin and PLP more effectively mitigate free radical generation than the individual molecule. These findings were further confirmed by the ITC binding study. These results suggest that a combination of melatonin and PLP could be a better therapeutic approach for the amelioration of stress induced oxidative damages in cardiac and hepatic tissues with an improved pyridoxine metabolism.

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer’s disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (−11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p

Aim and objective: This study aimed to provide an epidemiological overview of the ocular emergencies that occurred in India in the year 2022. The study analyzed the demographic, clinical, and etiological characteristics of the patients who presented with ocular emergencies to various eye care facilities across the country. The study also evaluated the outcomes and complications of ocular emergencies and identified the risk factors and preventive measures for reducing their incidence and severity. Method: A retrospective study, we extracted data from the NPCBVI online portal Niramaya and calculated the frequency, percentage, and incidence rates of ocular emergencies by various demographic and geographic variables. Results: More males (55.9%) than females (44.1%) are blind in India. The age group with the highest frequency of blindness is 15–49 years (40%), followed by 50–69 years (30%), ≥70 years (20%) and

Lean combustion is environment friendly with low NOX emissions providing better fuel efficiency in a combustion system. However, approaching towards lean combustion can make engines more susceptible to an undesirable phenomenon called lean blowout (LBO) that can cause flame extinction leading to sudden loss of power. During the design stage, it is quite challenging for the scientists to accurately determine the optimal operating limits to avoid sudden LBO occurrences. Therefore, it is crucial to develop accurate and computationally tractable frameworks for online LBO prediction in low NOX emission engines. To the best of our knowledge, for the first time, we propose a deep learning approach to detect the transition to LBO in combustion systems. In this work, we utilize a laboratory-scale swirl-stabilized combustor to collect acoustic data for different protocols. For each protocol, starting far from LBO, we gradually move towards the LBO regime, capturing a quasi-static time series dataset at different conditions. Using one of the protocols in our dataset as the reference protocol, we find a transition state metric for our trained deep learning model to detect the imminent LBO in other test protocols. We find that our proposed approach is more precise and computationally faster than other baseline models to detect the transition to LBO. Therefore, we endorse this technique for monitoring the operation of lean combustion engines in real time.

Background: Efficacy of balloon mitral valvuloplasty (BMV) in low gradient severe rheumatic mitral stenosis (MS) is not very well defined. This study was undertaken to evaluate the outcomes of BMV in low gradient severe rheumatic MS. Methods: Severe MS was defined as mitral valve area 0.05). Ninety percent (n = 36) patients improved in NFLG group in comparison to 70 % (n = 14) in LFLG group (p

A positive parity sequence of ΔI=2 γ transitions has been identified above Iπ=9/2+ state (Ex=2019 keV) in 115Sb through in-beam γ ray spectroscopic technique. Rotational features of this sequence are found similar to a low-K decoupled band. Observation of this newly identified low-K decoupled band, along with the earlier reported strongly coupled high-K band in this nucleus, provides the first experimental evidence for prolate-oblate shape coexistence associated with g9/2 proton-hole configuration around Z=50 shell closure. Experimental results are reproduced reasonably well in the frameworks of the projected shell model and the total Routhian surface calculations.

Mycobacterium tuberculosis (Mtb), causative agent of tuberculosis (TB) and non-tubercular mycobacterial (NTM) pathogens such as Mycobacterium abscessus are one of the most critical concerns worldwide due to increased drug-resistance resulting in increased morbidity and mortality. Therefore, focusing on developing novel therapeutics to minimize the treatment period and reducing the burden of drug-resistant Mtb and NTM infections are an urgent and pressing need. In our previous study, we identified anti-mycobacterial activity of orally bioavailable, non-cytotoxic, polycationic phosphorus dendrimer 2G0 against Mtb. In this study, we report ability of 2G0 to potentiate activity of multiple classes of antibiotics against drug-resistant mycobacterial strains. The observed synergy was confirmed using time-kill kinetics and revealed significantly potent activity of the combinations as compared to individual drugs alone. More importantly, no re-growth was observed in any tested combination. The identified combinations were further confirmed in intra-cellular killing assay as well as murine model of NTM infection, where 2G0 potentiated the activity of all tested antibiotics significantly better than individual drugs. Taken together, this nanoparticle with intrinsic antimycobacterial properties has the potential to represents an alternate drug candidate and/or a novel delivery agent for antibiotics of choice for enhancing the treatment of drug-resistant mycobacterial pathogens.

Fibrosis characterized by excess accumulation of extracellular matrix (ECM) due to complex cell-ECM interactions plays a pivotal role in pathogenesis. Herein, we employ the pancreatic ductal adenocarcinoma (PDAC) model to investigate dynamic alterations in nanomechanical attributes arising from the cell-ECM interactions to study the fibrosis paradigm. Several segregated studies performed on cellular and ECM components fail to recapitulate their complex collaboration. We utilized collagen and fibronectin, the two most abundant PDAC ECM components, and studied their nanomechanical attributes. We demonstrate alteration in morphology and nanomechanical attributes of collagen with varying thicknesses of collagen gel. Furthermore, by mixing collagen and fibronectin in various stoichiometry, their nanomechanical attributes were observed to vary. To demonstrate the dynamicity and complexity of cell-ECM, we utilized Panc-1 and AsPC-1 cells with or without collagen. We observed that Panc-1 and AsPC-1 cells interact differently with collagen and vice versa, evident from their alteration in nanomechanical properties. Further, using nanomechanics data, we demonstrate that ML-based techniques were able to classify between ECM as well as cell, and cell subtypes in the presence/absence of collagen with higher accuracy. This work demonstrates a promising avenue to explore other ECM components facilitating deeper insights into tumor microenvironment and fibrosis paradigm.

Due to the industrial revolution and, thereby with, the emergence of Industry 4.0, there has been an impact on the marketing of business firms, enabling them to digitally transform and adopt Marketing 4.0 practices supported by smart technologies. One of these is Big Data Analytics (BDA), which enables a firm to improve its marketing practices. The main objective of this study is to evaluate how integrating big data technology improves the marketing strategies of Indian FMCG companies operating in a dynamic and highly competitive market distinguished by its size and diversity, constantly changing consumer behaviour, and Marketing 4.0 trends. This study adopts a systematic approach to coding an interview with seasoned Indian FMCG professionals to explain the capabilities of Big Data in molding marketing practices. A framework is constructed based on the same. The theoretical and practical implications are discussed to visualize its applicability in business. Further, the Resource-based View (RBV) theory is discussed for describing the insights into the role and adoption of Big Data by Indian FMCG firms for enhancing performance and achieving competitiveness, along with demonstrating its benefits for decision-making, customer loyalty and internal capability assessment.

The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with disease development in individuals affected by DENV infection. Additionally, the study aimed to discover potential biomarkers that could indicate severe dengue infection and determine the most suitable timeframe for predicting the severity of these biomarkers during the acute stage of dengue infections. We conducted a temporal analysis of the daily viral load and cytokine levels in 60 hospitalized dengue patients until discharge. Our findings reveal a distinct cytokine profile (elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 and decreased IL-12, MIP-1β) on the third day after symptom onset is predictive of severe dengue in secondary dengue infection. The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.

This study is aimed to investigate the unsteady two-dimensional combined forced and natural convective motion of MHD Maxwell liquid passing a stretched surface. Non-Newtonian feature of the liquid is portrayed with the ‘upper convected Maxwell fluid’ model. A prearranged surface ‘temperature’ at the boundary is considered. ‘Similarity transformations’ are applied to find the self-similar solutions and then the altered ‘equations’ are numerically solved with the help of ‘Runge-Kutta method with shooting technique’. The behaviours of ‘flow’ and ‘heat’ transportation characters for diverse foremost ‘parameters’ are examined and discussed in detail for clear understanding about the non-Newtonian flow features and related thermal field. The interesting behaviours of flow and heat transfer characters warrant further studies of this problem for other type of situations. Due to unsteadiness, ‘velocity and temperature’ are seen to reduce for ‘buoyancy aided and opposed’ flows. Also, it is noted that for ‘buoyancy aided and opposed flows’, liquid velocity diminishes for rising ‘Hartmann number’. The influences of mounting ‘Maxwell parameter’ are to delay fluid velocity for either value of mixed convection parameter. However, for this case temperature is improved. Owing to mixed convection, liquid velocity increases but the temperature reduces within the ‘boundary layer’ area. Here lies the significance of the present study as this result is very much helpful for industrial applications for cooling purpose of different devices.

Newtonian nanoliquid flow passing a nonlinearly stretched surface in attendance of shear flow under ‘blowing/suction’ has been measured. For passive control of the flow, zero flux of nanoparticles at the border has been considered. Two-phase liquid replica for nanoliquid is used. ‘Similarity transformations’ are used to alter main ‘partial differential equations’ into ‘ordinary differential equations’. With the help of 4th order Runge-Kutta method and ‘shooting technique’, solutions of the leading equations are obtained numerically. ‘Wall shear stress’ and ‘mass transfer’ coefficient rise but ‘heat transfer coefficient’ reduces for mounting strain rate ‘parameter’. ‘Temperature’ of the liquid diminishes but fluid's ‘velocity’ and concentration rise with growing ‘suction/injection parameter’. Temperature of the liquid goes up but fluid's ‘velocity’ reduces with the enhancement of ‘nonlinear stretching parameter’. According to the results presented here it is very clear that the relevant ‘parameters’ influence ‘flow, heat and mass’ transportation appreciably.

This article describes the significance of ‘Stefan suction/blowing’ on the forced flow of nanoliquid past the surface of a ‘plate’ with temperature-obeying ‘thermal conductivity’ and ‘fluid viscosity’ with ‘zero nanoparticle flux’ at the ‘plate’ that has not till been attended by anyone and thus it points to the originality of present investigation and here lies the novelty of our work. Nanofluid flow is modeled with the help of ‘Buongiorno's two-phase model’ which contains the instantaneous virtue of thermophoresis diffusion and Brownian movement. This investigation shows that the speed of heat transport is remarkably augmented by the variable ‘thermal conductivity’ and variable ‘viscosity parameters’ which is the main contribution of this research. Due to changeable viscosity, reducing nature of velocity as well as the reducing nature of concentration of the nanoparticles near the ‘plate’ are observed. Due to Stefan's blowing parameter, fluid velocity augments but ‘temperature’ is observed to reduce for mounting values of Stefan's blowing parameter. 3.2 % reduction in skin-friction coefficient is noted when variable viscosity parameter reduces from -6 to -8. Moreover, 7.1 % reduction in heat transfer as well as mass transfer is noted when the variable thermal conductivity parameter rises from 0.2 to 0.4. The consequence of this inspection exposes a variation of exciting diversity which claims extra exploration of the present study.

Objectives: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. Methods: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. Results: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. Conclusion: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more effective vaccine for typhoid fever. Here, we cloned and expressed S. Typhi outer membrane protein A (OmpA). The conjugation of Vi-polysaccharide with OmpA was carried out by the carbodiimide (EDAC) method employing ADH as a linker. Total Ig and IgG generated against OmpA, and Vi polysaccharide was quantified by ELISA. Vi polysaccharide alone induced very low levels of Vi polysaccharide antibody. Vi-OmpA conjugate (Vi-conjugate) elicited a robust immune response compared to Vi polysaccharide alone and showed booster response. Further, IgG was only evoked by Vi-OmpA conjugate, not with Vi polysaccharide alone. OmpA antibody induction in both the Vi-OmpA conjugate and OmpA were similar level. Taken together, we show that OmpA as a carrier protein conjugated to Vi polysaccharide is immunogenic. We predict OmpA antibodies will contribute protection along with antibodies generated by Vi-polysaccharide. Past and current literature supports that OmpA is highly conserved protein not only among Salmonellae but entire Enterobacteriacea family with 96–100% identity.

Summary: Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th–97.5th centile) observed were: serum T4: μg/dL (5.23–12.31), TSH: μg/mL (0.52–4.16) and serum prolactin: ng/mL (5.13–37.35), LH: mIU/mL (2.75–20.68), FSH: mIU/mL 2.59–15.12), serum total testosterone: ng/mL (0.06–0.68), fasting insulin: mIU/mL (1.92–39.72), morning cortisol: μg/dL (4.71–19.64), DHEAS:μg/dL (50.61–342.6) and SHBG: nmol/L (21.37–117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p

Background: Psychosocial factors such as stress have been previously implicated as a risk factor for cardiovascular diseases (CVDs). There is little evidence regarding the prevalence of stress among patients with acute myocardial infarction (AMI). Methods: A total of 903 patients with AMI enrolled in the North Indian ST-Segment Elevation Myocardial Infarction (NORIN-STEMI) registry were included in this study. Perceived stress in these subjects was evaluated using the Perceived Stress Scale-10 questionnaire while the World health Organization (WHO-5) Well-being Index was used to evaluate psychological well-being. All these patients were followed up for one month and major adverse cardiac events (MACE) were determined. Results: A majority of patients with AMI had either severe (478 [52.9%]) or moderate stress (347 [38.4%]) while low stress levels were observed in 78 [8.6%] patients. Additionally, most of the patients with AMI (478 [53%]) had WHO-5 well-being index

Antisense oligonucleotides (ASOs) are short synthetic nucleic acids that recognize and bind to complementary RNA to modulate gene expression. It is well established that single-stranded, phosphorothioate-modified ASOs enter cells independent of carrier molecules, primarily via endocytic pathways, but that only a small portion of internalized ASO is released into the cytosol and/or nucleus, rendering the majority of ASO inaccessible to the targeted RNA. Identifying pathways that can increase the available ASO pool is valuable as a research tool and therapeutically. Here, we conducted a functional genomic screen for ASO activity by engineering GFP splice reporter cells and applying genome-wide CRISPR gene activation. The screen can identify factors that enhance ASO splice modulation activity. Characterization of hit genes uncovered GOLGA8, a largely uncharacterized protein, as a novel positive regulator enhancing ASO activity by ∼2-fold. Bulk ASO uptake is 2- to 5-fold higher in GOLGA8-overexpressing cells where GOLGA8 and ASOs are observed in the same intracellular compartments. We find GOLGA8 is highly localized to the trans-Golgi and readily detectable at the plasma membrane. Interestingly, overexpression of GOLGA8 increased activity for both splice modulation and RNase H1-dependent ASOs. Taken together, these results support a novel role for GOLGA8 in productive ASO uptake.

In the wake of the COVID-19 pandemic, respiratory tract infections have emerged as a significant global threat, yet their impact on public health was previously underappreciated. This study investigated the antiviral efficacy of the nano-coating agent BARRIER90, composed of silicon-quaternary ammonium compound and a naturally derived biopolymer, against three distinct respiratory viruses: Influenza A (H1N1), Adenovirus Type 1, and Enterovirus-Coxsackie B1. BARRIER90 exhibited robust and sustained virucidal activity, persisting up to 90 days post-coating, against the enveloped virus, Influenza A, with significant reduction in viral plaques. Contrastingly, its efficacy against non-enveloped viruses revealed transient activity against Enterovirus-Coxsackie B1, with almost no antiviral activity observed against Adenovirus Type 1. These findings indicate the potential of antimicrobial coatings in mitigating viral transmission through contaminated surfaces (fomites), which harbour pathogenic viruses for longer periods. Antimicrobial coatings may facilitate infection control in various settings, including healthcare facilities and shared workspaces.

Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi and it is reportedly associated with up to 20 % of hospitalized cases of febrile illnesses. The major challenge of vaccine development is the lack of identified antigens that can induce both heterotypic and homotypic immunity including the production of antibodies, cytotoxic T lymphocyte, and helper T lymphocytes. We employed a comprehensive immunoinformatic prediction algorithm to identify immunogenic epitopes of the 56-kDa type-specific cell membrane surface antigen and surface cell antigen A of O. tsutsugamushi to select potential candidates for developing vaccines and diagnostic assays. We identified 35 linear and 29 continuous immunogenic B-cell epitopes and 51 and 27 strong-binding T-cell epitopes of major histocompatibility complex class I and class II molecules, respectively, in the conserved and variable regions of the 56-kDa type-specific surface antigen. The predicted B- and T-cell epitopes were used to develop immunogenic multi-epitope candidate vaccines and showed to elicit a broad-range of immune protection. A stable interactions between the multi-epitope vaccines and the host fibronectin protein were observed using docking and simulation methods. Molecular dynamics simulation studies demonstrated that the multi-epitope vaccine constructs and fibronectin docked models were stable during simulation time. Furthermore, the multi-epitope vaccine exhibited properties such as antigenicity, non-allergenicity and ability to induce interferon gamma production and had strong associations with their respective human leukocyte antigen alleles of world-wide population coverage. A correlation of immune simulations and the in-silico predicted immunogenic potential of multi-epitope vaccines implicate for further investigations to accelerate designing of epitope-based vaccine candidates and chimeric antigens for development of serological diagnostic assays for scrub typhus.

Summary: Investigating the rheology of 2D materials such as clays is of growing interest in various applications as it dictates their flowability and structural stability. Clay minerals present unique rheological properties, especially when in suspension. This study explores the effect of functionalizing bentonite clay with betaines of variable carbon chain lengths on the rheological properties of clay slurries to analyze their interactions in suspension. The results show that these zwitterion-functionalized clays exhibit higher viscosity, storage moduli, and flow stresses due to the formation of three-dimensional networks and increased aggregation caused by intercalation. The structural properties of the clay slurries are also found to be pH-sensitive. Additionally, XRD and SEM analyses support the proposed intercalation of the clays. The findings suggest the potential application of small-chain betaine functionalized clays in engineering and energy applications. Overall, this study provides insight into predicting the stability and strength of functionalized clay suspensions.

Ready-to-eat breakfast cereals (RTEBCs) have been developed from low-amylose rice by incorporating germinated green gram and bhimkol flour. A four variable central composite design (CCD) was used to evaluate the effects of independent variables on product responses, viz. blend ratio (80:10:10–60:30:10) of low-amylose rice flour, germinated green gram and bhimkol), screw speed (200–400 rpm), barrel temperature (90–130 °C) and feed moisture content (10.5–20.5%, wet basis), respectively. Extrudates developed in the optimized condition showed acceptable physic-chemical properties viz. EI (5.5) and BS (0.215 N/mm2), WAI (483.21 g/100 g), WSI (46.22 g/100 g), PV (484 cp) and FV (154 cp). The extrudates were found to have dietary fibre content and vitamin B1 content of 5.16% and 0.847 μg/g, respectively. MTT-proliferation study showed 75.45% survivality for extrudate made of low amylose rice blended with germinated green gram and bhimkol flour at maximum concentration of 50 mg/ml, respectively. Thus it was demonstrated that germinated green gram and bhimkol could be extruded to have a healthy RTBCs as well as weaning food.

Summary: Understanding the cell biological mechanisms that enable tumor cells to persist after therapy is necessary to improve the treatment of recurrent disease. Here, we demonstrate that transient receptor potential channel 6 (TRPC6), a channel that mediates calcium entry, contributes to the properties of breast cancer stem cells, including resistance to chemotherapy, and that tumor cells that persist after therapy are dependent on TRPC6. The mechanism involves the ability of TRPC6 to regulate integrin α6 mRNA splicing. Specifically, TRPC6-mediated calcium entry represses the epithelial splicing factor ESRP1 (epithelial splicing regulatory protein 1), which enables expression of the integrin α6B splice variant. TRPC6 and α6B function in tandem to facilitate stemness and persistence by activating TAZ and, consequently, repressing Myc. Therapeutic inhibition of TRPC6 sensitizes triple-negative breast cancer (TNBC) cells and tumors to chemotherapy by targeting the splicing of α6 integrin mRNA and inducing Myc. These data reveal a Ca2+-dependent mechanism of chemotherapy-induced persistence, which is amenable to therapy, that involves integrin mRNA splicing.

Aim: To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41–49%) regardless of baseline diabetes. Methods: We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model. Results: We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p

Introduction: The Cancer Genome Atlas cohort of endometrial carcinoma (TCGA-UCEC) includes almost 40% TP53-mutants encompassing missense and truncated variants. TCGA revealed ‘POLE’, characterized by POLE gene bearing exonuclease domain mutation (EDM), as the prognostically best molecular profile. The worst profile was characterized by TP53-mutated Type 2 cancer requiring adjuvant therapy having cost implications in low-resource settings. We aimed to find more ‘POLE-like’ favourable subgroups by searching TCGA cohort, especially within TP53 mutated risk group, that could eventually avoid adjuvant treatment in resource-poor settings. Method: Our study was an in-silico survival analysis performed on the TCGA-UCEC dataset using SPSS statistical package. TP53 and POLE mutations, microsatellite instability (MSI), time-to-event and clinicopathological parameters were compared among 512 endometrial cancer cases. Deleterious POLE-mutations were identified by Polyphen2. Progression free survival was studied using Kaplan-Meier plots keeping original ‘POLE’ as comparator. Result: In presence of wild type (WT)-TP53, other deleterious POLE-mutations behaved like POLE-EDM. Only truncated and not missense TP53 benefitted from POLE/MSI overlap. However, TP53 missense mutation, Y220C, was found to be as favourable as ‘POLE’. Overlapping POLE, MSI and WT-TP53 also performed favourably. Truncated TP53 overlapped with POLE and/or MSI, TP53 Y220C alone and, WT-TP53 overlapped with POLE and MSI both, were named ‘POLE-like’ for prognostically behaving like the comparator ‘POLE’. Conclusion: Obesity being a lesser frequent event in low and middle-income countries (LMICs), relative proportion of women with lower BMI and Type 2 endometrial cancers may be high. Identification of ‘POLE-like’ groups may facilitate therapeutic de-escalation in some TP53-mutated cases - a novel option. Instead of 5% (POLE-EDM), potential beneficiary would then comprise 10% (POLE-like) of TCGA-UCEC.

Clustered outbreaks of multi-drug resistant (MDR) Shigella are on the rise among men who have sex with men (MSM). Identification of MDR sub-lineages is critical for clinical management and public health interventions. Here, we describe a novel MDR sub-lineage of Shigella flexneri isolated from an MSM patient without a travel history in Southern California. Detailed genomic characterization of this novel strain would serve as a reference to aid monitoring and future outbreak investigation of MDR Shigella among MSM.

Quasi-elastic (QEL) scattering measurements have been performed using a 28Si projectile off a 90Zr target at energies around the Coulomb barrier. A Bayesian analysis within the framework of coupled channels (CC) calculations is performed in a large parameter space of quadrupole and hexadecapole deformations (β2 and β4) of 28Si. Our results unambiguously show that 28Si is an oblate shaped nucleus with β2=-0.38±0.01 which is in excellent agreement with results from electromagnetic probes. The sign and magnitude of quadrupole deformation along with a precise value of hexadecapole deformation (β4=+0.03±0.01) of 28Si have been determined for the first time using QEL scattering. A remarkable agreement is obtained between the experimental and calculated β4 values of 28Si based on Skyrme-Hartree-Fock method. The present results demonstrate the strong sensitivity of the quasi-elastic scattering to the sign and magnitude to the ground state deformation parameters, thus affirming its suitability to be used for rare exotic nuclei using low intensity RIBs.

The next wave of unprecedented urbanisation is expected to occur in South Asia and Africa, with India being the most populous country. India's urbanisation choices will influence the success of the three global agendas: New Urban Agenda, Sustainable Development Goals, and the Paris Agreement. Sustainable urban transport is vital in delivering United Nations Sustainable Development Goal 11 (SDG11) on inclusive and sustainable urbanisation. SDG11 includes dimensions such as equity, gender equality, health, employment, and climate change. Through a mixed-methods approach, the paper develops an assessment framework to investigate: ‘What are the roles of existing urban transport interventions in delivering SDG11?’ in two Indian cities: Surat (an industrial city of 5.9 million) and Udaipur (a tourist city of 0.8 million) across three interrelated transport roles: providing Inclusive Access, delivering Climate-Resilient Development, and delivering Context-Sensitive Planning. Each urban transport interaction is assigned synergy (+1), trade-off (−1) or mixed impacts (−/+1). The paper finds that current transport interventions in Surat & Udaipur largely result in trade-offs across all three themes Inclusive Access (−1 for Surat & Udaipur), Climate Vulnerability (−1 for Surat & Udaipur), and Context-Sensitive Planning (−1 for Surat & +1 for Udaipur).

Summary: Maximizing the production of heterologous biomolecules is a complex problem that can be addressed with a systems-level understanding of cellular metabolism and regulation. Specifically, growth-coupling approaches can increase product titers and yields and also enhance production rates. However, implementing these methods for non-canonical carbon streams is challenging due to gaps in metabolic models. Over four design-build-test-learn cycles, we rewire Pseudomonas putida KT2440 for growth-coupled production of indigoidine from para-coumarate. We explore 4,114 potential growth-coupling solutions and refine one design through laboratory evolution and ensemble data-driven methods. The final growth-coupled strain produces 7.3 g/L indigoidine at 77% maximum theoretical yield in para-coumarate minimal medium. The iterative use of growth-coupling designs and functional genomics with experimental validation was highly effective and agnostic to specific hosts, carbon streams, and final products and thus generalizable across many systems.

In recent years, the use of nanotechnology has shown great potential to enhance plant growth by combating stress tolerance. One of the major stress factors in agriculture is soil salinity, which adversely affects crop productivity and quality. The development of engineered nanoparticles (ENPs) has opened new avenues for alleviating salinity stress in plants. These ENPs usually made of biocompatible materials that have been shown to enhance plant growth and reduce salt stress-induced damage by improving their nutrient uptake, water balance, and anti-oxidative defense mechanisms. Several studies have reported the effectiveness of ENPs in enhancing plant growth and yield under salt stress conditions. For instance, silica nanoparticles were found to increase the chlorophyll content and photosynthetic efficiency of salt-stressed tomato plants, resulting in higher biomass and fruit yield. Similarly, chitosan nanoparticles were shown to increase the water-use efficiency of maize plants and reduce the accumulation of sodium ions in leaves under salt stress conditions. Furthermore, the ENPs can act as carriers for plant growth-promoting compounds, such as nutrients, hormones, or bioactive molecules, to enhance plant growth and stress tolerance.Despite the promising results, the use of ENPs in agriculture raises concerns about their potential environmental impacts and safety for human health. The fate and transport of ENPs in soil and water systems, as well as their potential toxicity to non-target organisms, need to be carefully evaluated. This review analyzes the use of ENPs as a tool for mitigating salinity stress in plants and offers a promising strategy that requires further research and development to optimize their efficacy and safety in agricultural applications.

This paper deals with the flow of non-Newtonian nanoliquid past an unsteady stretched exterior in attendance of Stefan blowing/suction. Model for Casson liquid has been taken into account to represent the non-Newtonian liquid. Two phase fluid replica for nanofluid has been considered. Similarity alterations are applied to transform the leading pdes (partial differential equations) to ordinary ones. Runge–Kutta method of order four has been used to solve the altered equations numerically with the help of shooting technique. Wall shear stress, heat and mass transfer coefficients diminish with the rise in unsteadiness. Fluid's velocity and temperature are found to rise with the enhancement in Stefan blowing/suction parameter. Temperature of the fluid rises but fluid's velocity diminishes for the rising values of Casson parameter. Basically, the pertinent parameters affect the stream, warmth and accumulation transport significantly which can be viewed by the figures and tables presented here and also by their physical analysis.

Background: There is an increasing prevalence of coronary artery disease (CAD) in younger individuals. Lipid biomarkers such as lipoprotein-a (Lp-a), Apo A1, Apo B and Paraoxonase-1 (PON1) serve as important risk predictors for development of CAD. There is little evidence regarding the role of lipid biomarkers and their genetic polymorphisms in young (

Background: Genetic polymorphism in MMPs are associated with multiple adverse CV events. There is little evidence regarding role of MMPs and their genetic polymorphisms in young (

The baseline approaches on satellite image segmentation problem suffer from issues like sensitivity towards initialization, local optima solutions, a predefined number of output clusters, single-objective optimization, etc. To solve these challenges, this study proposes a unique pixel-level Multi-Spectral (MS) very high resolution (VHR) image segmentation algorithm based on variable-length multi-objective genetic clustering. We propose a new approach to update solutions by retaining variable length property throughout the optimization process. The resulting clustering algorithm contains a set of near-Pareto-optimal solutions. A map that has a scale of less than 1/10000 is called a large-scale map. We propose a large-scale change detection technique as an application of the proposed image segmentation algorithm. Solving Land-use/Land-Cover (LULC) change detection problems in a congested area is a complex task. This study considers the dataset from Pleiades-HR 1B, and Landsat 5 TM sensors in the experimental study. An extensive quantitative and qualitative analysis is performed to validate the superior performance of the proposed method with different state-of-the-art techniques.

The Youngest Toba Tuff (YTT, 74 ka ago) is considered as the product of one of the largest super-volcanic events in the Quaternary period, which possibly caused a disastrous effect on the climate and hominid habitation. Here, we report a rare occurrence of an ∼ 2 cm YTT ash bed in the Barakar-Damodar Late Quaternary sediments, Eastern India, and the Microlith toolkits that were found in the sedimentary deposits above the ash layer. The high silica content of the glass shards with bubble walls, blocky, rod-shaped structures, and pumice morphology, are similar to other YTT ash deposits. The sedimentary facies associated with the ash layer show a transition from lacustrine to fluvial depositional environments. Sedimentological, petrographical, mineralogical, geochemical, and magnetic properties suggest the ash was deposited in a lacustrine environment. Moreover, the discovery of the ash bed, the occurrence of in-situ Bovid species, and microlith assemblages in the Barakar-Damodar Valley add to our understanding of late Pleistocene depositional environments, hominin occupations, and possible local migration across eastern India during the Last Glacial Maximum (LGM) period.

Background: Vaccination against COVID 19 and observing COVID appropriate behavior are effective measures to control, manage and prevent COVID-19 infection. With India starting its adolescent vaccination program, this study aimed to explore the adolescents’ perception of vaccination, their COVID-appropriate behavior, compliance with two doses of COVID-19 vaccines and the experienced side effects following vaccination. Methods: A longitudinal survey was conducted among 440 adolescents visiting the COVID Vaccination Center (CVC) of a tertiary hospital in West Bengal. In the survey, adolescents were asked about family socio-demographic characteristics, their opinions on COVID-19 vaccines, and COVID-19 Appropriate Behavior (CAB) practices. Voluntary participants were given a questionnaire to fill and a telephonic interview was taken regarding side effects experienced following the vaccination and their compliance to both doses of vaccine. Results: The majority of adolescents (99.3%) had taken vaccines by their own wish. The reason for willingness to take the vaccine was the fear of being infected with COVID-19 infection (50.5%). Maximum adolescents got information regarding the COVID vaccination program through the internet (41.8%) followed by family members (30.5%). The majority of adolescents (70.9%) had a good perception of COVID-19 vaccination. A significant number of adolescents (44.8%) strongly disagreed with the statement that they don't need to follow COVID appropriate behavior after vaccination. Conclusion: The majority of adolescents had a good perception regarding COVID-19.

The aim of this study is to present the existence of two-dimensional steady boundary layer flow of hybrid nanofluid over a diverging channel in the occurrence of an externally applied magnetic field. The walls of the channel are absorbent and subjected to either suction or injection of equivalent amount of the same type of fluid on both the walls. By using appropriate similarity transformations the governing non-linear partial differential equations (PDEs) along with boundary conditions are transformed into a set of non-linear ordinary differential equations (ODEs). The obtained non-linear ODEs with modified boundary conditions are solved using the traditional and competent shooting method. The option of flow under boundary layer approximations in a divergent channel is inspected with the hybrid nanofluid model. The significance of this study is that in the attendance of a magnetic field with appropriate value of magnetic parameter flow separation for hybrid nanofluid flow through a diverging channel can be prohibited. This study discloses that if mass suction exceeds a certain amount then only boundary layer flow is possible and as magnetic parameter increases, the requirement of mass suction for boundary layer flow diminishes.

Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma expression and recruits T cells to the tumor microenvironment, ultimately yielding durable systemic T cell responses. Interrogation of longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase of intratumoral CXCR3 transcripts that was restricted to responding patients, underscoring the clinical relevance of tumor-infiltrating CXCR3+ immune cells. In this study, we sought to understand if the addition of DNA-encodable CXCL9 could augment the anti-tumor immune responses driven by intratumoral IL-12. We show that localized IL-12 and CXCL9 treatment reshapes the tumor microenvironment to promote dendritic cell licensing and CD8+ T cell activation. Additionally, this combination treatment results in a significant abscopal anti-tumor response and provides a concomitant benefit to anti-PD-1 therapies. Collectively, these data demonstrate that a functional tumoral CXCR3/CXCL9 axis is critical for IL-12 anti-tumor efficacy. Furthermore, restoring or amplifying the CXCL9 gradient in the tumors via intratumoral electroporation of plasmid CXCL9 can not only result in efficient trafficking of cytotoxic CD8+ T cells into the tumor but can also reshape the microenvironment to promote systemic immune response.

Inflammation is a complicated physiological process that results in a variety of disorders. Several inflammatory mediators are produced during this process, which is responsible for long-term inflammatory conditions like osteoarthritis, rheumatoid arthritis, asthma, cancer, and neurological disorders. Inflammatory mediators are produced by an arachidonic acid pathway that gives us several anti-inflammatory targets. The most commonly used medications are NSAIDs to treat inflammation by inhibiting cyclooxygenase (COX) and lipoxygenase enzymes (5-LOX). However, this therapy is associated with adverse events like gastrointestinal disorders, renal failure, etc., limiting its use. Therefore, novel, efficacious, and safer anti-inflammatory agents are prerequisites for inhibiting both cyclooxygenase and lipoxygenase pathways. Though several synthetic analogs are under development, natural products may act as a potential source to identify novel molecules and herbal remedies. Valuable contributions have been made in this direction by the scientific communities. This review article briefly discusses the implications of phytochemicals and bioactive fractions in the development of dual COX-LOX inhibitors while highlighting different classes of phytoconstituents such as tannins, steroids, flavonoids, alkaloids, terpenoids, among others, that showed significant dual COX-LOX inhibition.