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In industrial applications, among several varieties of semiconductor devices available, a silicon-controlled rectifier (SCR) is often used in managing and protecting various systems with different applications. Hence, it is of the utmost importance to design a control system which can operate over a range of electrical loads without any modifications in its hardware and/or software. This paper analyzes and investigates in detail the power circuit effects on conduction delay and SCR functioning. Moreover, two different commonly used driving systems for SCR application have been introduced, discussed, and evaluated. Concerning driving systems, here, three aspects have paramount importance and are consequently taken into consideration, namely the driver system losses, the conduction delay, and in particular, some power quality indices. The conduction delay is a parameter of great importance, as being able to control and reduce it to the minimum allowed by the application can bring significant practical advantages (both in terms of application and economic terms, as better summarized in the article). Theoretical analysis has been performed, followed and verified by simulation studies and, for some cases, laboratory experimental test results are presented which provide credibility to the study.

Plastic recycling has become more important than ever as the globe struggles with growing environmental issues. This research explores the significant environmental impact of recycling plastic and its growing relevance. The pervasive material known as plastic presents a complex risk to both human health and ecosystems in contemporary life. It exacerbates problems including marine pollution, habitat damage, and wildlife entanglement because of its persistence in landfills and seas, which leads to serious ecological deterioration. In addition, producing plastic uses a lot of energy and produces a lot of greenhouse gas emissions, which exacerbate climate change. Through the use of multi-criteria decision making (MCDM), this study emphasizes how vital it is to support recycling activities in order to protect the environment and promote a sustainable future. The elimination and choice ex-pressing reality (ELECTRE) approach is used to rank the alternatives in this proposed research study that employs bipolar dual hesitant fuzzy sets (BDHFs). The most efficient and versatile outranking method for making decisions is the BDHF-ELECTRE approach. The weights of environment, economic, social, technical, and finally safety is computed using the entropy distance metric. The economic factor received the highest score of 0.2945 among the other factors since economic considerations are crucial in choosing the most efficient plastic recycling method, as they ensure sustainability, cost-effectiveness, resource allocation, and overall feasibility in managing plastic waste. The decision-makers determined that the mechanical recycling approach ought to be prioritized over all others for the efficient recycling of plastic waste. The robustness of the system is examined in the sensitive and comparative analyses. The proposed MCDM technique thus presents a viable solution, mitigating the adverse effects of plastic waste by conserving resources, reducing energy consumption, and curbing pollution., (© 2024. The Author(s).)

Introduction Stroke-associated pneumonia (SAP) frequently complicates stroke and is associated with significant mortality. Clinicians often use physiological variables within the National Early Warning Score (NEWS) when diagnosing and prescribing antibiotics for SAP, but little is known of its association with mortality. We investigated the relationship of the NEWS 2 score and its components (respiratory rate, heart rate, temperature, oxygen requirement, oxygen saturation and alertness level) prior to antibiotic initiation, with time-to-mortality in SAP. Methods We included patients with SAP (n=389) from a single hyperacute stroke unit. Diagnosis of SAP was made if pneumonia occurred within 7 days of hospital admission. Kaplan-Meier survival curves were generated to assess NEWS 2 parameters influencing survival at pre-defined time periods (1 year and 5 years). The association of these parameters on time-to-mortality were analysed using multivariable Cox regression models to account for a set of pre-specified potential confounders. Results The median age was 80y (71y-87y) and median NIHSS was 7 (IQR 4-17). Mortality within 1 year was 52.4% and 65.8% within 5 years. In the multivariable analyses, time-to-mortality was independently associated with respiratory rate (HR 1.04, 95% CI 1.01 to1.08, p=0.009) and total NEWS 2 score (HR 1.13, 95% CI 1.06 to 1.21, p=<0.001). Conclusions In patients with SAP, higher respiratory rate and total NEWS 2 score prior to antibiotic initiation were independently associated with time-to-mortality. Further studies are warranted to identify potential opportunities for intervention and ultimately guide treatment to improve outcomes in SAP patients., (S. Karger AG, Basel.)

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we performed multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing, along with spatial profiling. We identified tumor microenvironmental features previously described to associate with therapy response. We identified five malignant cell programs, including undifferentiated, intermediate, differentiated, epithelial-to-mesenchymal transition, and cycling programs, which were associated with differential epigenetic plasticity and clinical outcomes, and for which we inferred candidate transcription factor regulons. Furthermore, we revealed diverse spatial localizations of malignant cells expressing their associated transcriptional programs and predicted their significant interactions with microenvironmental cell types. We validated our findings in three external single-cell RNA-seq and three bulk RNA-seq studies. Altogether, our findings advance the understanding of EAC heterogeneity, disease progression, and therapeutic response., Competing Interests: E.M.V.: Advisory/Consulting: Enara Bio, Manifold Bio, Monte Rosa, Novartis Institute for Biomedical Research, Serinus Bio, TracerDx Research support: Novartis, BMS, Sanofi, NextPoint Equity: Tango Therapeutics, Genome Medical, Genomic Life, Enara Bio, Manifold Bio, Microsoft, Monte Rosa, Riva Therapeutics, Serinus Bio, Syapse, TracerDx Travel reimbursement: None Patents: Institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation; intermittent legal consulting on patents for Foaley & Hoag Editorial Boards: Science Advances A.J.A. has consulted for Anji Pharmaceuticals, Affini-T Therapeutics, Arrakis Therapeutics, AstraZeneca, Boehringer Ingelheim, Kestrel Therapeutics, Merck & Co., Inc., Mirati Therapeutics, Nimbus Therapeutics, Oncorus, Inc., Plexium, Quanta Therapeutics, Revolution Medicines, Reactive Biosciences, Riva Therapeutics, Servier Pharmaceuticals, Syros Pharmaceuticals, T-knife Therapeutics, Third Rock Ventures, and Ventus Therapeutics. A.J.A. holds equity in Riva Therapeutics and Kestrel Therapeutics. A.J.A. has research funding from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Deerfield, Inc., Eli Lilly, Mirati Therapeutics, Nimbus Therapeutics, Novartis, Novo Ventures, Revolution Medicines, and Syros Pharmaceuticals.

Currently, the treatment of various human ailments is based on different therapeutic approaches including traditional and modern medicine systems. Precision nutrition has come into existence as an emerging approach considering the diverse aspects such as age, sex, genetic and epigenetic makeup, apart from the pathophysiological conditions. The continuously and gradually evolving disciplines of genomics about nutrition have elucidated the importance of genetic variations, epigenetic information, and expression of myriads of genes in disease progression apart from the involvement in modulating therapeutic responses. Further, the investigations have presented the considerable role of gut microbiota comprising of commensal and symbionts performing innumerable activities such as release of bioactive molecules, defense against pathogenic microbes, and regulation of immunity. Noteworthy, the characteristics of the microbiome change depending on host attributes, environmental factors, and habitat, in addition to diet, and therefore can be employed as a biomarker to unravel the response to given food. The specific diet and the components thereof can be suggested for supporting the enrichment of the desired microbial community to some extent as an important part of precision nutrition to achieve not only the goal of human health but also of healthy aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Singh, Hu, Singh, Solanki, Vijayaraghavan, Srivastav, Joshi, Kumari, Singh, Wang and Kumar.)

The introduction of pharmaceuticals into aquatic ecosystems can lead to the generation of antibiotic-resistant bacteria. This paper employed molecular dynamics simulations to examine the interactions between cationic/anionic surfactants and two antibiotics or drugs, namely, ciprofloxacin and azithromycin. The analysis focused on many factors to elucidate the mechanism by which the surfactant bilayer molecular structure affects the selected antibiotics. These factors include the tilt angle, rotational angle of the surfactants, electrostatic potential, and charge density along the bilayers. Our molecular-level investigation of the adsorption mechanisms of hydrophobic (azithromycin) and hydrophilic (ciprofloxacin) drugs on the cationic/anionic surfactant bilayer offers a crucial understanding for comprehending the optimal selection of surfactants for effectively separating antibiotics., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Stroke is a leading cause of morbidity and mortality in humans. Most strokes are ischemic in nature and early recanalization of occluded vessels determines good outcomes. Recanalization of occluded vessels depends on many angiographic and demographic features. These factors need to be identified for better patient overall outcomes. Better preoperative knowledge of factors can help in customizing our treatment approach and explaining the prognosis to the guardians of the patients. We aim to share our institutional experience with mechanical thrombectomy (MT) for stroke and studied factors that affect an angiographic recanalization of vessels . A retrospective single-center study was conducted involving 104 patients who underwent MT at our institution between January 2016 and December 2019. Patient demographics, baseline characteristics, pre- and postprocedural imaging findings, and other clinical data were meticulously reviewed. We divided patients into successful recanalization (modified thrombolysis in cerebral ischemia [mTICI] 2b or 3) and unsuccessful recanalization (mTICI 2a or 1) groups and various factors were analyzed to evaluate their impact on recanalization rates. In the univariate analysis, a significant association was observed between successful recanalization and several factors: the absence of rheumatic heart disease (RHD) as a risk factor ( p  = 0.035), the presence of a hyperdense vessel sign ( p  = 0.003), and the use of treatment methods including aspiration ( p  = 0.031), stent retriever ( p  = 0.001), and Solumbra ( p  = 0.019). However, in the multivariate analysis, none of these factors exhibited statistical significance. The presence of RHD is a risk factor associated with poor angiographic recanalization in all three MT treatment modalities. Based on the above variables we can guide the patients/relatives prior to MT procedure for their better outcome and risk-benefit ratio., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The technological landscape for industrial processes handling asphaltene is evolving at a rapid pace due to the increase in the extraction of heavy crude oil. The main underlying challenges in this regard are the flow assurance, the recovery of the spent solvent, and the sophisticated extractor setup required to develop the process to an industrial scale. The number of studies focused on the handling of the asphaltene at the atomic and molecular scales is growing enormously in order to identify new sustainable solvents for the effective extraction of asphaltene from heavy crude oil or oil-bearing sands. This Perspective focuses on the importance of density functional theory and molecular dynamics simulations to explore the broader range of asphaltene inhibitors, e.g., nanoparticles, ionic liquids, and deep eutectic solvents, to prevent asphaltene precipitation. We provide a concise overview of the major accomplishments, analyze the aspects that require attention, and highlight the path-breaking studies having a significant impact on the process of chemical enhanced oil recovery from heavy crude oil reservoirs primarily based on atomistic and molecular simulations., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Background and Purpose: Mechanical thrombectomy is the standard treatment modality for flow restoration in acute ischemic stroke. In cases of persistent occlusion, the optimal number of retrieval attempts before considering procedure termination is currently undetermined and is a topic for research. Therefore in this study, we studied the impact of the number of stent retrieval maneuvers on the recanalization of vessels., Methods: In this retrospective single-center observational study we included 52 patients with large vessel occlusion who underwent stent retriever mechanical thrombectomy. Successful recanalization rate was defined as modified TICI (Thrombolysis in Cerebral Infarction) 2b or 3., Result: The overall successful recanalization rate was 44.24%. The recanalization rate per stent retrieval attempt was the highest in 1st attempt (28.84%) and no recanalization was observed with the 3rd, 5th, and 6th attempts (p<0.001). At most 6 retrieval attempts were used., Conclusions: After two retrieval attempts, 91% of the patients were successfully recanalized and other after the 5th attempt could not result in recanalization., Competing Interests: Nil, (Copyright © 2024 Bheru Dan Charan, Shailesh B Gaikwad, Savyasachi Jain, Ajay Garg, Leve Joseph Devarajan Sebastian, M V Padma Srivastava, Rohit Bhatia, Awadh Kishore Pandit, Shashank Sharad Kale. Published by Vilnius University Press.)

Background: Mechanical thrombectomy has been established as a safe, standard and effective treatment option for occlusions of the proximal segment of the middle cerebral artery (MCA), as demonstrated in numerous studies. However, performing thrombectomy in the M2 divisions of MCA presents inherent challenges. In this institutional experience, we aim to delineate the recanalisation rates achieved through mechanical thrombectomy in cases involving the M2 segment of the MCA., Methods: We conducted a retrospective analysis of patients who underwent thrombectomy due to M2 MCA occlusions in the period from January 2018 to December 2021. Various factors affecting recanalisation rates were assessed., Results: A total of 15 patients with M2 segment occlusions of the middle cerebral artery were included in the study, comprising 11 in the superior division and 4 in the inferior division. The successful recanalisation rate was 72.33%, with notably higher success observed in cases of inferior division occlusion. The primary outcome of our study was the mTICI recanalisation status, categorised as successful recanalisation (mTICI = 2b or mTICI = 3) and unsuccessful recanalisation (mTICI = 1 or mTICI = 2a) and mRS at 6 months. None of the predictors assessed reached statistical significance., Conclusions: Mechanical thrombectomy demonstrates favourable efficacy and recanalisation rates in cases of M2 MCA division occlusion. Notably, inferior division occlusions exhibit a higher likelihood of successful recanalisation., Competing Interests: The authors declare that they have no competing interests, (Copyright © 2024 Bheru Dan Charan, Shailesh B Gaikwad, Savyasachi Jain, Ajay Garg, Leve Joseph Devarajan Sebastian, M V Padma Srivastava, Rohit Bhatia, Awadh Kishore Pandit, Shashank Sarad kale. Published by Vilnius University Press.)

The ability of neat deep eutectic solvents (DESs) to influence protein structure and function has gained considerable interest due to the unstable nature of enzymes or therapeutic proteins, which are often exposed to thermal, chemical, or mechanical stresses when handled at an industrial scale. In this study, we simulated a model globular protein, lysozyme, in water and six choline chloride-based DES using molecular dynamics simulations, to investigate the structural changes in various solvent environments, giving insights into the overall stability of lysozyme. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) of the C- α backbone indicated that most DESs induced a less flexible and rigid lysozyme structure compared to water. The radius of gyration and end-to-end distance calculations pointed towards higher structural compactness in reline and levuline, while the structure of lysozyme considerably expanded in oxaline. Protein-solvent interactions were further analysed by hydrogen bonding interactions and radial distribution functions (RDF), which indicated a higher degree of lysozyme-hydrogen bond donor (HBD) interactions compared to lysozyme-choline hydrogen bonding. Surface area analysis revealed an overall % increase in total positive, negative, donor, and acceptor surface areas in malicine and oxaline compared to water and other DESs, indicating the exposure of a larger number of residues to interactions with the solvent. Reline, levuline, and polyol-based DESs comparatively stabilized lysozyme, even though changes in the secondary/tertiary structures were observed.Communicated by Ramaswamy H. Sarma.

Quantum dots (QDs) are a class of remarkable materials that have garnered significant attention since their initial discovery. It is noteworthy to mention that it took approximately a decade for these materials to be successfully implemented in practical applications. While QDs have demonstrated notable optical properties, it is important to note that these attributes alone have not rendered them a feasible substitute for traditional organic dyes. Furthermore, it is worth noting that the substance under investigation exhibited inherent toxicity and instability in its initial state, primarily due to the presence of a heavy metal core. In the initial stages of research, it was observed that the integration of nanocomposites had a positive impact on the properties of QDs. The discovery of these nanocomposites was motivated by the remarkable properties exhibited by biocomposites found in nature. Recent discoveries have shed light on the potential utilization of QDs as a viable strategy for drug delivery, offering a promising avenue to enhance the efficacy of current pharmaceuticals and pave the way for the creation of innovative therapeutic approaches. The primary objective of this review was to elucidate the distinctive characteristics that render QDs highly suitable for utilization as nanocarriers. In this study, we will delve into the multifaceted applications of QDs as sensing nanoprobes and their utilization in diverse drug delivery systems. The focus of our investigation was directed toward the utilization of QD/polymer composites in sensing applications, with particular emphasis on their potential as chemical sensors, biosensors, and physical sensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard., (© 2023. Kunming Institute of Botany, CAS.)

Globally, substantial research into endophytic microbes is being conducted to increase agricultural and environmental sustainability. Endophytic microbes such as bacteria, actinomycetes, and fungi inhabit ubiquitously within the tissues of all plant species without causing any harm or disease. Endophytes form symbiotic relationships with diverse plant species and can regulate numerous host functions, including resistance to abiotic and biotic stresses, growth and development, and stimulating immune systems. Moreover, plant endophytes play a dominant role in nutrient cycling, biodegradation, and bioremediation, and are widely used in many industries. Endophytes have a stronger predisposition for enhancing mineral and metal solubility by cells through the secretion of organic acids with low molecular weight and metal-specific ligands (such as siderophores) that alter soil pH and boost binding activity. Finally, endophytes synthesize various bioactive compounds with high competence that are promising candidates for new drugs, antibiotics, and medicines. Bioprospecting of endophytic novel secondary metabolites has given momentum to sustainable agriculture for combating environmental stresses. Biotechnological interventions with the aid of endophytes played a pivotal role in crop improvement to mitigate biotic and abiotic stress conditions like drought, salinity, xenobiotic compounds, and heavy metals. Identification of putative genes from endophytes conferring resistance and tolerance to crop diseases, apart from those involved in the accumulation and degradation of contaminants, could open new avenues in agricultural research and development. Furthermore, a detailed molecular and biochemical understanding of endophyte entry and colonization strategy in the host would better help in manipulating crop productivity under changing climatic conditions. Therefore, the present review highlights current research trends based on the SCOPUS database, potential biotechnological interventions of endophytic microorganisms in combating environmental stresses influencing crop productivity, future opportunities of endophytes in improving plant stress tolerance, and their contribution to sustainable remediation of hazardous environmental contaminants., (© 2023. The Author(s).)

Oil spills and subsequent cleanup by oil-water separation remain a global concern. For the first time, corn silk-derived cellulose acetate (CSCA) and polyacrylonitrile (PAN) composite nanofiber are reported to create a superhydrophobic oil-water sequestration membrane. CA : PAN solutions with various PAN concentrations were evaluated for viscosity and conductivity. A CSCA nanofiber membrane was fabricated through electrospinning, which was superhydrophobic and oleophilic in water. Scanning electron microscope, energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis/differential scanning calorimetry were used to analyze the membrane's morphological features. CSCA nanofibers formed a highly spherical bead with a maximum contact angle of 156° (>120°) in pure water solutions, demonstrating their superhydrophobicity. This study found that membranes can remove oil from oil-water mixtures and emulsions, as gravity is the only force required for propelling the system. Mineral oil had the highest oil sorption capability (908%), while toluene had the lowest (664%). For mineral oil-water mixtures, the CSCA membrane has the greatest separation flux at a maximum of 442 L/m 2 /h and the best separation efficiency at up to 99.67%. These findings provide strong support for using an as-prepared CSCA nanofiber membrane as a viable reusable oil sorbent in oil spill cleaning.

Interferon-gamma (IFN-γ) is a type II interferon produced primarily by T cells and natural killer cells. IFN-γ induces the expression of inducible nitric oxide synthase (NOS2) to catalyze Nitric Oxide (NO) production in various immune and non-immune cells. Excessive IFN-γ-activated NO production is implicated in several inflammatory diseases, including peritonitis and inflammatory bowel diseases. In this study, we screened the LOPAC® 1280 library in vitro on the H6 mouse hepatoma cell line to identify novel non-steroidal small molecule inhibitors of IFN-γ-induced NO production. Compounds with the highest inhibitory activity were validated, which led to identifying the lead compounds: pentamidine, azithromycin, rolipram, and auranofin. Auranofin was the most potent compound determined based on IC 50 and goodness of fit analyses. Mechanistic investigations revealed that majority of the lead compounds suppress the IFN-γ-induced transcription of Nos2 without negatively affecting NO-independent processes, such as the IFN-γ-induced transcription of Irf1, Socs1 and MHC class 1 surface expression. However, all four compounds lower IFN-γ-induced reactive oxygen species amounts. In addition, auranofin significantly reduced IFN-γ-mediated NO and IL6 production in resident as well as thioglycolate-elicited peritoneal macrophages (PMs). Finally, in vivo testing of the lead compounds in the pre-clinical DSS-induced ulcerative colitis mice model revealed pentamidine and auranofin to be the most potent and protective lead compounds. Also, pentamidine and auranofin greatly increase the survival of mice in another inflammatory model: Salmonella Typhimurium-induced sepsis. Overall, this study identifies novel anti-inflammatory compounds targeting IFN-γ-induced NO-dependent processes to alleviate two distinct inflammatory models of disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Existing water and wastewater treatment techniques are becoming increasingly difficult to employ due to the discovery of new toxins, the rapid development of population and industrial activities, and the limited quantity of water resources. Treatment of wastewater is a critical need in modern civilization due to a scarcity of water resources and rising industrial activity. Some of the techniques utilized include adsorption, flocculation, filtration, and others, although they are only used for primary wastewater treatment. However, the development and deployment of modern wastewater management with high efficiency and low capitalization are critical in terms of mitigating the environmental consequences of waste. The employment of different nanomaterials in the treatment of wastewater has opened up a world of possibilities for heavy metal and pesticide removal, as well as the treatment of microbes and organic contaminants in wastewater. Nanotechnology is a rapidly evolving technology because of certain nanoparticle's outstanding physiochemical and biological capabilities as contrasted to bulk counterparts. Secondly, it has been established that this is a cost-effective treatment strategy with significant potential in wastewater management, transcending the limitations imposed by currently existing technology. Advances in nanotechnology to reduce water contamination have been presented in this review, including the use of various nanomaterials such as nanocatalysts, nanoadsorbents, and nanomembranes in the treatment of wastewater containing organic contaminants, hazardous metals, and virulent pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This paper discusses the design and development of a low-cost virtual reality (VR) based flight simulator with cognitive load estimation feature using ocular and EEG signals. Focus is on exploring methods to evaluate pilot's interactions with aircraft by means of quantifying pilot's perceived cognitive load under different task scenarios. Realistic target tracking and context of the battlefield is designed in VR. Head mounted eye gaze tracker and EEG headset are used for acquiring pupil diameter, gaze fixation, gaze direction and EEG theta, alpha, and beta band power data in real time. We developed an AI agent model in VR and created scenarios of interactions with the piloted aircraft. To estimate the pilot's cognitive load, we used low-frequency pupil diameter variations, fixation rate, gaze distribution pattern, EEG signal-based task load index and EEG task engagement index. We compared the physiological measures of workload with the standard user's inceptor control-based workload metrics. Results of the piloted simulation study indicate that the metrics discussed in the paper have strong association with pilot's perceived task difficulty., Competing Interests: The authors declare that the contents of the article are in agreement with the ethics described in http://biblio.unibe.ch/portale/elibrary/BOP/jemr/ethics.html and that there is no conflict of interest regarding the publication of this paper., (Copyright (©) 2023 Hebbar, P. A., Vinod, S., Shah, A.K., Pashilkar, A. A., Biswas, P.)

Our goal in this manuscript is to advance the assessment and treatment of monkey species in neuroscience research. We hope to begin a discussion and establish baseline data on how complications are identified and treated. We surveyed the neuroscience research community working with monkeys and compiled responses to questions about investigator demographics, assessment of animal wellbeing, treatment choices, and approaches to mitigate risks associated with CNS procedures and promote monkey health and wellbeing. The majority of the respondents had worked with nonhuman primates (NHP) for over 15 y. Identification of procedure-related complications and efficacy of treatment generally rely on common behavioral indices. Treatments for localized inflammatory responses are generally successful, whereas the treatment success for meningitis or meningoencephalitis, abscesses, and hemorrhagic stroke are less successful. Behavioral signs of pain are treated successfully with NSAIDs and opioids. Our future plans are to collate treatment protocols and develop best practices that can be shared across the neuroscience community to improve treatment success rates and animal welfare and therefore science. Human protocols can be used to develop best practices, assess outcomes, and promote further refinements in treatment practices for monkeys to enhance research outcomes.

One of the major constituents of heavy oil is asphaltenes. They are responsible for numerous problems in petroleum downstream and upstream processes, such as catalyst deactivation in heavy oil processing and blocking pipes while transporting crude oil. Probing the efficiency of new nonhazardous solvents in separating asphaltenes from crude oil is key to avoid conventional volatile and hazardous solvents by replacing these conventional solvents with new ones. In this work, we have investigated the efficiency of ionic liquids to separate asphaltenes from organic solvents (such as toluene and hexane) using molecular dynamics simulations. Triethylammonium-dihydrogen-phosphate and triethylammonium acetate ionic liquids are considered in this work. Various structural and dynamical properties are calculated, such as radial distribution function, end-to-end distance, trajectory density contour, and diffusivity of asphaltene in the ionic liquid-organic solvent mixture. Our results explain the role of anions, i.e., dihydrogen-phosphate and acetate ions, in separating asphaltene from toluene and hexane. Our study provides an important revelation about the dominant role played by the IL anion in intermolecular interactions which depends on the type of solvent (i.e., toluene or hexane) in which the asphaltene is present. The anion induces enhanced aggregation in the asphaltene-hexane mixture compared to the asphaltene-toluene mixture. The molecular insights obtained within this study on the role played by ionic liquid anion in asphaltene separation are key for the preparation of new ionic liquids for asphaltene precipitation applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as "CTs", are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance., Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included., Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69-0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68-0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75-0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF., Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JD has obtained honoraria from Medtronic, BI, BMS, Diaicchi Sankyo, Bayer, Pfizer. In addition, research support was also obtained from Pfizer and BMS. AK has obtained honoraria from Medtronic, Bayer and Abbott Inc. AC has received honoraria from BMS, Pfizer, AstraZeneca and Boeringher Ingelheim and research grants from Pfizer., (© European Stroke Organisation 2022.)

There are numerous elements of daily life where plastic is employed, yet it is uncertain exactly when it will deteriorate. Poly-(3-hydroxybutyrate) (PHB), a biodegradable polymer, is viewed as a possible substitute for synthetic plastics made from petroleum. With Pseudomonas putida SS9, the current study sought to enhance operational conditions and nutritional factors to enhance PHB production. To maximize the impacts of operational factors, a combination of response surface modeling (RSM) and artificial neural networks (ANN) has been applied. PHB content was used as the response while the interaction effects of the factors were examined. The optimal parameters for PHB synthesis were further tested in a lab scale fermentor. Under optimal conditions, 13.83 g/L of C, 0.57 g/L of N, 0.59 g/L of P, the maximal productivity of PHB obtained with Pseudomonas putida SS9 is 12.89 g/L after 84 h. A mean square value of 15.7 with P < 0.0001 were obtained from the ANOVA results of quadratic polynomial model using RSM. The same construct was employed in MATLAB software to train a feed-forward ANN using the back-propagation approach, generating 12.88 g/L. The data indicated that a properly trained ANN model outperforms the RSM model in prediction. Furthermore, employing dairy waste (cheese whey) as a low-cost feedstock resulted in an equally proportionate PHB yield of 12.02 g/L. Therefore, cheese whey appeared to be a viable alternative carbon source over optimized synthetic media., Competing Interests: Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

NLRP3 is a cytoplasmic receptor protein, which initiates caspase-1 mediated inflammatory immune response upon detection of invading pathogen or a wide array of internal distress signals. Several gain-of function mutations of NLRP3 cause hereditary disorder of cold-induced hyper-inflammation known as familial cold autoinflammatory syndrome-1 (FCAS1). Although, caspase-1 activation and downstream interleukin-1β/interleukin-18 maturation are common effectors in pathophysiology of this disorder, molecular mechanisms of how exposure to subnormal temperature triggers mutant NLRP3-inflammsome activity is not understood. Here, we show that endogenous NLRP3 is in complex with HSC70 (HSPA8), and this interaction is reduced upon exposure to cold. FCAS-causing NLRP3-L353P and NLRP3-R260W mutants show enhanced interaction with HSC70. Upon exposure to subnormal temperature, NLRP3-L353P and NLRP3-R260W show enhanced inflammasome formation, increased caspase-1 activation and reduced interaction with HSC70. Knockdown of HSC70 results in increased inflammasome formation by L353P and R260W mutants of NLRP3. Our results suggest that interaction with HSC70 suppresses inflammasome formation by FCAS-causing NLRP3 mutants at physiological temperature, and loss of this inhibitory association at subnormal temperature causes aggravated inflammasome formation and caspase-1 activation leading to interleukin-1β maturation. These results provide evidence for HSC70 being a cold-sensor and a temperature-dependent regulator of inflammatory signaling by FCAS-causing NLRP3 mutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Familial cold autoinflammatory syndrome (FCAS) is a subset of heritable autoinflammatory disorders wherein inflammatory symptoms aggravate upon exposure of the individual to subnormal temperature. In the past two decades, several mutations in various genes such as NLRP3, NLRP12, PLCG2 and NLRC4 have been identified that cause cold-triggered inflammation. However, our understanding of the mechanisms by which cells perceive subnormal temperature, and what keeps the inflammation under check until exposure to low temperature, is very limited. We hypothesise that recognition of FCAS-associated mutants as misfolded polypeptides by temperature-sensitive HSC70 (HSPA8) chaperone determines the FCAS phenotype. At 37 °C, HSC70 would interact with the mutant proteins, keeping them almost inactive, and loss of interaction at low temperature due to a conformational change in HSC70 would lead to their activation. The proposed mechanism of low temperature sensing in the context of FCAS may have wider implications for HSC70 as a cold temperature sensor in various pathological conditions where symptoms get aggravated upon exposure to low temperature., (© 2021 Federation of European Biochemical Societies.)

Microorganisms are an important component of the ecosystem and have an enormous impact on human lives. Moreover, microorganisms are considered to have desirable effects on other co-existing species in a variety of habitats, such as agriculture and industries. In this way, they also have enormous environmental applications. Hence, collections of microorganisms with specific traits are a crucial step in developing new technologies to harness the microbial potential. Microbial culture collections (MCCs) are a repository for the preservation of a large variety of microbial species distributed throughout the world. In this context, culture collections (CCs) and microbial biological resource centres (mBRCs) are vital for the safeguarding and circulation of biological resources, as well as for the progress of the life sciences. Ex situ conservation of microorganisms tagged with specific traits in the collections is the crucial step in developing new technologies to harness their potential. Type strains are mainly used in taxonomic study, whereas reference strains are used for agricultural, biotechnological, pharmaceutical research and commercial work. Despite the tremendous potential in microbiological research, little effort has been made in the true sense to harness the potential of conserved microorganisms. This review highlights (1) the importance of available global microbial collections for man and (2) the use of these resources in different research and applications in agriculture, biotechnology, and industry. In addition, an extensive literature survey was carried out on preserved microorganisms from different collection centres using the Web of Science (WoS) and SCOPUS. This review also emphasizes knowledge gaps and future perspectives. Finally, this study provides a critical analysis of the current and future roles of microorganisms available in culture collections for different sustainable agricultural and industrial applications. This work highlights target-specific potential microbial strains that have multiple important metabolic and genetic traits for future research and use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Newly detected atrial fibrillation (NDAF) following an ischemic stroke or transient ischemic attack is often paroxysmal in nature. While challenging to detect, extended electrocardiographic (ECG) monitoring is often used to identify NDAF which has resource implications. Prognostic risk scores have been derived which may stratify the risk of NDAF and inform patient selection for ECG monitoring approaches after ischemic stroke/transient ischemic attack., Aim: The overall aim was to identify risk scores that were derived and/or validated to predict NDAF after ischemic stroke/transient ischemic attack and evaluate their performance., Summary of Review: A systematic literature review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, with application of the Quality Assessment of Diagnostic Accuracy-2 tool. Published studies, which derived and validated clinical risk scores in patients with ischemic stroke/transient ischemic attack, or externally validated an existing score to predict NDAF after ischemic stroke/transient ischemic attack, were considered and independently screened by two reviewers. Twenty-one studies involving 23 separate cohorts were analyzed from which 17 integer-based risk scores were identified. The overall frequency of NDAF was 9.7% (95% confidence intervals 8%-11.5%; I 2  = 98%). The performance of the scores varied widely among derivation and validation cohorts (area under the receiver operating characteristic curve (AUC) 0.54-0.94); scores derived from stroke cohorts (12 scores) appeared to perform better (AUC 0.7-0.94) than those derived from non-stroke cohorts (five scores; AUC 0.53-0.79). The scores also varied considerably in their complexity, ascertainment, component variables, participant characteristics, outcome definition, and ease of application limiting their generalizability and utility., Conclusion: Overall, the risk scores identified performed variably in their discriminative ability and the utility of these scores to predict NDAF in clinical practice remains uncertain. Further studies are required using larger prospective cohorts and randomized control trials to evaluate the usefulness of such scores for clinical decision making and preventative intervention.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India., Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases., Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Aggregation phenomena arise predominantly due to self-organisation of molecules to form supramolecular assemblies leading to restriction of intramolecular motions. In the present study, the solvent-induced aggregation of salicylaldehyde azine ester (SAE) was comprehensively investigated through experimental techniques, and classical molecular dynamics simulations (MDS). The emission spectra and particle sizes of SAE in THF-water mixtures confirmed the formation of nanoaggregates. The interaction of SAE aggregates with the solvent mixture was studied using Fourier-transform Infrared spectroscopy. The optical microscopy images and surface morphology analysis reinforced the nanoaggregate formation of SAE in solvent mixtures with increasing water fractions. The average number of H-bonds, diffusion coefficients and trajectory density contours of the aggregates were investigated through MDS studies, which provided atomistic perceptions into the formation of rod-like SAE nanoaggregates. The combined results of experimental and theoretical studies offer deeper insights into the self-aligning tendency of SAE in THF-water mixtures.

Introduction: Globally, pedestrians are one of the most vulnerable road-user groups. Their vulnerability increases while crossing the road at controlled intersections during the "don't walk" phase. Previous literature shows that driver yielding behavior has an association with pedestrian safety at intersections. Though several studies have explored driver yielding behavior towards pedestrians at conflict points, evidence on how pedestrian actions influence driver yielding behavior at intersections is yet to be investigated., Method: To pursue this end, a binary logistic regression model was developed using the collected data to explore the effect of non-compliant pedestrian characteristics and their road crossing behavior on driver yielding behavior towards pedestrians at six controlled intersections of Dhaka, Bangladesh. The data were collected through videography survey., Results: Results showed that drivers were more likely to yield to pedestrians who were female, crossing in a group, carrying baggage, not using a mobile, making some hand gesture to the driver, or crossing by rolling gap strategy., Practical Applications: These findings add new insights for transportation planners into the complex interaction between vehicles and pedestrians at busy controlled intersections, and thus would help to make a pedestrian friendly street., (Copyright © 2022.)

An important feature of several neurodegenerative diseases is the formation of pathological structures containing aggregated proteins. The autophagy receptor optineurin/OPTN is frequently observed in these structures. The role played by optineurin in these aggregates is not clear. In this study, we explored whether optineurin has a cytoprotective role in the cells having mutant protein aggregates. We overexpressed mutant huntingtin having 97 glutamine repeats (mHtt) and mutant ataxin-3 having 130 glutamine repeats (mAtax-3) in wild-type and optineurin-deficient neuronal (N2A) and non-neuronal cells (Optn-/- mouse embryonic fibroblasts) and determined the percentage of dead cells with mutant protein aggregates. Optineurin-deficient cells having mHtt or mAtax-3 aggregates showed higher cell death as compared to wild-type cells having mutant protein aggregates. Confocal microscopy revealed that optineurin formed a shell around mHtt and mAtax-3 aggregates through its C-terminal domain. The C-terminal domain of optineurin, which lacks LC3-interacting region required for autophagy, was necessary and sufficient to reduce cytotoxicity of mHtt and mAtax-3 aggregates. Our results show that in the absence of optineurin, mutant protein aggregates are highly toxic, revealing an autophagy-independent cytoprotective function of optineurin, which is mediated by its C-terminal domain., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Competing Interests: There are no conflicts of interest.

To study, compare and analyse the trend of allergic rhinitis incidence post COVID-19 pandemic in a tertiary care hospital in Patna Bihar. This is a retrospective observational study done at Patna medical college from January to June 2020. The number of patients with signs and symptoms of allergic rhinitis post pandemic (March-July2020) were compared to preceding three months (Jan 2020-March2020). Chi square test was employed to know and infer whether the change in trend of incidence is statistically significant. There is decrease in trend of allergic rhinitis in our study at our centre. P  < .01. Decrease in pollution due to lockdown and increased use of mask and increase indoor activities may be the reason for decreasing trend of allergic rhinitis., (© Association of Otolaryngologists of India 2020.)

Introduction: Infection after stroke is associated with unfavorable outcome. Randomized controlled studies did not show benefit of preventive antibiotics in stroke but lacked power for subgroup analyses. Aim of this study is to assess whether preventive antibiotic therapy after stroke improves functional outcome for specific patient groups in an individual patient data meta-analysis., Patients and Methods: We searched MEDLINE (1946-7 May 2021), Embase (1947-7 May 2021), CENTRAL (17th September 2021), trial registries, cross-checked references and contacted researchers for randomized controlled trials of preventive antibiotic therapy versus placebo or standard care in ischemic or hemorrhagic stroke patients. Meta-analysis was performed by a one-step and two-step approach. Primary outcome was functional outcome adjusted for age and stroke severity. Secondary outcomes were infections and mortality., Results: 4197 patients from nine trials were included. Preventive antibiotic therapy was not associated with a shift in functional outcome (mRS) at 3 months (OR1.13, 95%CI 0.98-1.31) or unfavorable functional outcome (mRS 3-6) (OR0.85, 95%CI 0.60-1.19). Preventive antibiotics did not improve functional outcome in pre-defined subgroups (age, stroke severity, timing and type of antibiotic therapy, pneumonia prediction scores, dysphagia, type of stroke, and type of trial). Preventive antibiotics reduced infections (276/2066 (13.4%) in the preventive antibiotic group vs. 417/2059 (20.3%) in the control group, OR 0.60, 95% CI 0.51-0.71, p < 0.001), but not pneumonia (191/2066 (9.2%) in the preventive antibiotic group vs. 205/2061 (9.9%) in the control group (OR 0.92 (0.75-1.14), p = 0.450)., Discussion and Conclusion: Preventive antibiotic therapy did not benefit any subgroup of patients with acute stroke and currently cannot be recommended., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: WFW, JDV, CJS, AK, JH, LK, AM, AC, JJC, YR, MRAN, FAF, JAS, MGWD, PJN, DvdB declare no competing interests. DB is clinical advisor and stockholder in Argenica Therapeutics, a biotech company developing a neuroprotective drug., (© European Stroke Organisation 2021.)

Inflammation is strongly implicated in both injury and repair processes occurring after stroke. In this exploratory study we assessed the feasibility of repeated sampling of exhaled volatile organic compounds and performed an untargeted metabolomic analysis of plasma collected at multiple time periods after stroke. Metabolic profiles were compared with the time course of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Serial breath sampling was well-tolerated by all patients and the measurement appears feasible in this group. We found that exhaled decanal tracks CRP and IL-6 levels post-stroke and correlates with several metabolic pathways associated with a post-stroke inflammatory response. This suggests that measurement of breath and blood metabolites could facilitate development of novel therapeutic and diagnostic strategies. Results are discussed in relation to the utility of breath analysis in stroke care, such as in monitoring recovery and complications including stroke associated infection., (© 2021. The Author(s).)

Background: As the health systems around the world struggled to meet the challenges of COVID-19 pandemic, care of many non-COVID emergencies was affected., Aims: The present study examined differences in the diagnosis, evaluation and management of stroke patients during a defined period in the ongoing pandemic in 2020 when compared to a similar epoch in year 2019., Methods: The COVID stroke study group (CSSG) India, included 18 stroke centres spread across the country. Data was collected prospectively between February and July 2020 and retrospectively for the same period in 2019. Details of demographics, stroke evaluation, treatment, in-hospital and three months outcomes were collected and compared between these two time points., Results: A total of 2549 patients were seen in both study periods; 1237 patients (48.53%) in 2019 and 1312 (51.47%) in 2020. Although the overall number of stroke patients and rates of thrombolysis were comparable, a significant decline was observed in the month of April 2020, during the initial period of the pandemic and lockdown. Endovascular treatment reduced significantly and longer door to needle and CT to needle times were observed in 2020. Although mortality was higher in 2020, proportion of patients with good outcome were similar in both the study periods., Conclusions: Although stroke admissions and rates of thrombolysis were comparable, some work flow metrics were delayed, endovascular stroke treatment rates declined and mortality was higher during the pandemic study period. Reorganization of stroke treatment pathways during the pandemic has likely improved the stroke care delivery across the globe., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Occurrence of stroke has been reported among patients with COVID-19. The present study compares clinical features and outcomes of stroke patients with and without COVID-19., Methods: The COVID-19 Stroke Study Group (CSSG) is a multicentric study in 18 sites across India to observe and compare the clinical characteristics of patients with stroke admitted during the current pandemic period and a similar epoch in 2019. The present study reports patients of stroke with and without COVID-19 (CoVS and non-CoVS, respectively) seen between February 2020 and July 2020. Demographic, clinical, treatment, and outcome details of patients were collected., Results: The mean age and gender were comparable between the two groups. CoVS patients had higher stroke severity and extent of cerebral involvement on imaging. In-hospital complications and death were higher among CoVS patients (53.06% vs. 17.51%; P < 0.001) and (42.31% vs. 7.6%; P < 0.001), respectively. At 3 months, higher mortality was observed among CoVS patients (67.65% vs. 13.43%; P < 0.001) and good outcome (modified Rankin score [mRS]: 0-2) was seen more often in non-CoVS patients (68.86% vs. 33.33%; P < 0.001). The presence of COVID-19 and baseline stroke severity were independent predictors of mortality., Conclusions: CoVS is associated with higher severity, poor outcome, and increased mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and baseline stroke severity are independent predictors of mortality., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2021 Annals of Indian Academy of Neurology.)

Drug delivery empowered with nanotechnology manifests to be a superior therapy to cancer. Electrospun nanofibers cocooning anti-cancerous drugs have shown tremendous cytotoxicity towards various tumor cells, including breast, brain, liver, and lung cancer cells. This pristine drug delivery system, according to literature, desists showing any undesirable effects on other parts of the body and bestows several other benefits. From nature-derived Curcumin to laboratory-made Doxorubicin, literature proclaims many such drugs used in nanofibrous drug delivery. Also, multi-drug delivery has been reported to exhibit enhanced properties. The present review exhibits the unrealized potential of nanofibrous drug delivery in chemotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V.)

Gynaecological cancers are the major cause of cancer-related deaths in Indian women. The poor prognosis and lack of symptoms in the early stages make early cancer diagnosis difficult. The absence of mandatory screening programmes and the lack of awareness pose to be a real challenge in a developing economy as India. Prompt intervention is required to enhance cancer patient survival statistics and to lessen the social and financial burden. Conventional screening and cytological techniques employed currently have helped to reduce the incidence of cancers considerably. However, these tests offer low sensitivity and specificity and are not widely used for risk assessment, leading to inadequate early-stage cancer diagnosis. The accomplishment of Human Genome Project (HGP) has opened doors to exciting 'omics' platforms. Promising research in genomics and proteomics has revolutionized cancer detection and screening methodologies by providing more insights in the gene expression, protein function and how specific mutation in specific genes corresponds to a particular phenotype. However, these are incompetent to translate the information into clinical applicability. Various factors such as low sensitivity, diurnal variation in protein, poor reproducibility and analytical variables are prime hurdles. Thus the focus has been shifted to metabolomics, which is a much younger platform compared to genomics and proteomics. Metabolomics focuses on endpoint metabolites, which are final products sustained in the response to genetic or environmental changes by a living system. As a result, the metabolome indicates the cell's functional condition, which is directly linked to its phenotype. Metabolic profiling aims to study the changes occurred in metabolic pathways. This metabolite profile is capable of differentiating the healthy individuals from those having cancer. The pathways that a cell takes in turning malignant are exceedingly different, owing to the fact that transformation of healthy cells to abnormal cells is linked with significant metabolic abnormalities. This review is aimed to discuss metabolomics and its potential role in early diagnosis of gynaecological cancers, viz. breast, ovarian and cervical cancer.

Objectives: Accurate and timely diagnosis of pneumonia complicating stroke remains challenging and the diagnostic accuracy of chest X-ray (CXR) in the setting of stroke-associated pneumonia (SAP) is uncertain. The overall objective of this study was to evaluate the use of pulmonary computed tomography (CT) in diagnosis of suspected SAP., Materials and Methods: Patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH) were recruited within 24h of clinically suspected SAP and underwent non-contrast pulmonary CT within 48h of antibiotic initiation. CXR and pulmonary CT were reported by two radiologists. Pulmonary CT was used as the reference standard for final diagnosis of SAP. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and diagnostic odds ratio (OR) for CXR were calculated., Results: 40 patients (36 IS, 4 ICH) with a median age of 78y (range 44y-90y) and a median National Institute of Health Stroke Scale score of 13 (range 3-31) were included. All patients had at least one CXR and 35/40 patients (88%) underwent pulmonary CT. Changes consistent with pneumonia were present in 15/40 CXRs (38%) and 12/35 pulmonary CTs (34%). 9/35 pulmonary CTs (26%) were reported normal. CXR had a sensitivity of 58.3%, specificity of 73.9%, PPV of 53.8 %, NPV of 77.2 %, diagnostic OR of 3.7 (95% CI 0.7 - 22) and an accuracy of 68.5% (95% CI 50.7% -83.1%)., Discussion: CXR has limited diagnostic accuracy in SAP. The majority of patients started on antibiotics had no evidence of pneumonia on pulmonary CT with potential implications for antibiotic stewardship., Conclusions: Pulmonary CT could be applied as a reference standard for evaluation of clinical and biomarker diagnostic SAP algorithms in multi-center studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Human telomerase reverse transcriptase (hTERT) remains suppressed in most normal somatic cells. Resulting erosion of telomeres leads eventually to replicative senescence. Reactivation of hTERT maintains telomeres and triggers progression of >90% of cancers. However, any direct causal link between telomeres and telomerase regulation remains unclear. Here, we show that the telomere-repeat-binding-factor 2 (TRF2) binds hTERT promoter G-quadruplexes and recruits the polycomb-repressor EZH2/PRC2 complex. This is causal for H3K27 trimethylation at the hTERT promoter and represses hTERT in cancer as well as normal cells. Two highly recurrent hTERT promoter mutations found in many cancers, including ∼83% glioblastoma multiforme, that are known to destabilize hTERT promoter G-quadruplexes, showed loss of TRF2 binding in patient-derived primary glioblastoma multiforme cells. Ligand-induced G-quadruplex stabilization restored TRF2 binding, H3K27-trimethylation, and hTERT re-suppression. These results uncover a mechanism of hTERT regulation through a telomeric factor, implicating telomere-telomerase molecular links important in neoplastic transformation, aging, and regenerative therapy., Competing Interests: Declaration of interests S.C. is a scientific advisor for Rejuvas Biotech India Pvt. Ltd., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

GSK3β, a ubiquitously expressed Ser/Thr kinase, regulates cell metabolism, proliferation and differentiation. Its activity is spatially and temporally regulated dependent on external stimuli and interacting partners, and its deregulation is associated with various human disorders. In this study, we identify C3G (RapGEF1), a protein essential for mammalian embryonic development as an interacting partner and substrate of GSK3β. In vivo and in vitro interaction assays demonstrated that GSK3β and Akt are present in complex with C3G. Molecular modelling and mutational analysis identified a domain in C3G that aids interaction with GSK3β, and overlaps with its nuclear export sequence. GSK3β phosphorylates C3G on primed as well as unprimed sites, and regulates its subcellular localization. Over-expression of C3G resulted in activation of Akt and inactivation of GSK3β. Huntingtin aggregate formation, dependent on GSK3β inhibition, was enhanced upon C3G overexpression. Stable clones of C2C12 cells generated by CRISPR/Cas9 mediated knockdown of C3G, that cannot differentiate, show reduced Akt activity and S9-GSK3β phosphorylation compared to wild type cells. Co-expression of catalytically active GSK3β inhibited C3G induced myocyte differentiation. C3G mutant defective for GSK3β phosphorylation, does not alter S9-GSK3β phosphorylation and, is compromised for inducing myocyte differentiation. Our results show complex formation and reciprocal regulation between GSK3β and C3G. We have identified a novel function of C3G as a negative regulator of GSK3β, a property important for its ability to induce myogenic differentiation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The disposal of municipal solid waste (MSW) directly at landfills or open dump areas, without segregation and treatment, is a significant concern due to its hazardous contents of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and metal resistance genes (MGEs). The released leachate from landfills greatly effects the soil physicochemical, biological, and groundwater properties associated with agricultural activity and human health. The abundance of ARB, ARGs, and MGEs have been reported worldwide, including MSW landfill sites, animal husbandry, wastewater, groundwater, soil, and aerosol. This review elucidates the occurrence and abundance of ARB, ARGs, and MRGs, which are regarded as emerging contaminants (ECs). Recently, ECs have received global attention because of their prevalence in leachate as a substantial threat to environmental and public health, including an economic burden for developing nations. The present review exclusively discusses the demands to develop a novel eco-friendly management strategy to combat these global issues. This review also gives an intrinsic discussion about the insights of different aspects of environmental and public health concerns caused due to massive leachate generation, the abundance of antibiotics resistance (AR), and the effects of released leachate on the various environmental reservoirs and human health. Furthermore, the current review throws light on the source and fate of different ECs of landfill leachate and their possible impact on the nearby environments (groundwater, surface water, and soil) affecting human health. The present review strongly suggests the demand for future research focuses on the advancement of the removal efficiency of contaminants with the improvement of relevant landfill management to reduce the potential effects of disposable waste. We propose the necessity of the identification and monitoring of potential environmental and human health risks associated with landfill leachate contaminants.

The present research is focused on the application of glass beads (GBs) in fixed biofilm reactor (FBR) for the treatment of simulated methylene blue (MB) wastewater for 9 weeks under aerobic conditions. The COD of MB wastewater showed a reduction of 86.48% from 2000 to 270.4 mg/L, and BOD was declined up to 97.7% from 1095.5 to 25.03 mg/L. A drastic increase in the pH was observed until the 3rd week (8.5 to 8.28), and later, marginal changes between 8.30 ± 0.02 were noticed. A dramatic fluctuation was observed in ammonia concentration which increased (74.25 mg/L) up till the 2nd week, and from the 3rd week it started declining. In the 9th week, the ammonia concentration dropped to 16.5 mg/L. The color intensity increased significantly up till the 2nd week (259,237.46 Pt/Co) of the experiment and started decreasing slowly thereafter. The SEM-EDX analysis has shown the maximum quantity of carbon content in the GBs without biofilm, and then in the GB samples of 1st, and 9th-week old aerobic biofilms. Furthermore, Raman spectroscopy results revealed that the 9th-week GBs has a fine and strong MB peak and matched with that of the MB stock solution. Overall, the results have shown that the GBs filter media were suitable for the development of active biofilm communities for the treatment of dye wastewater. Thus, GBs-FBR system can be used for wastewater treatment to solve the current problem of industrial pollution in many countries and to protect the aquatic environment from dye pollution caused by the textile industry.

How to cite this article: Bhattacharyya M, Debnath AK, Todi SK. Clostridium difficile and Antibiotic-associated Diarrhea. Indian J Crit Care Med 2020;24(Suppl 4):S162-S167., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Background: Paroxysmal atrial fibrillation (PAF) is a frequent cause of recurrent stroke but can be difficult to detect because of its episodic and often asymptomatic nature. We sought to improve rate of PAF detection through a quality improvement project (QIP) to deliver early prolonged inpatient cardiac monitoring on the stroke unit (SU)., Methods: A structured protocol for cardiac monitoring using 5-day event recorders was established. 'In-house' cardiac monitoring was implemented. Performance data on this change in service was analysed prospectively and summary statistics obtained., Results: One-hundred and two ischaemic stroke (IS) patients undertook 5-day event recorder monitoring. Provision of monitors as an inpatient (IP) increased from 20% (pre-QIP pilot 2018) to 65.7% (during QIP). New AF was detected in 15 patients (14.7% vs 8.6% pre-QIP pilot 2018) with majority of new AF (13 patients; 19%) detected when monitors applied early (IP) after IS., Conclusion: Although this study had a number of limitations, it did demonstrate that early and prolonged non-invasive IP cardiac monitoring could be delivered 'in-house' on the SU and improve AF detection rates., (© Royal College of Physicians 2020. All rights reserved.)

The aggregation behavior of asphaltene in aqueous solution is systematically investigated based on a classical molecular dynamics study. In this work, a novel approach is adopted in order to investigate the structural and dynamical properties of the asphaltene nanoaggregates using different water models. The end-to-end distance of the asphaltene molecule is probed in order to understand the aggregation behavior in aqueous solution. The accuracy of different water models, that is, simple point charge, TIP4P-D, and TIP5P, is thoroughly investigated. In order to probe the dynamical properties of the asphaltene nanoaggregates, the transport coefficients, namely, diffusion coefficient and shear viscosity, are computed. The obtained results highlight the importance of using the appropriate water model in order to accurately study the aggregation behavior of asphaltene in aqueous solution., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Aim: To classify unrelated patients with juvenile onset primary open angle glaucoma (JOAG) into clinically useful phenotypes using cluster analysis., Methods: Out of the 527 unrelated patients with JOAG, the study included 414 patients who had all the phenotypic characteristics required for the study. A cluster analysis was performed to classify the patients based on their iris and angle morphology, age of onset, highest untreated intraocular pressure (IOP), worst mean deviation and greatest vertical cup disc ratio of the worst eye. The iris features were broadly classified into three groups: those with normal iris crypts (NIC), those with prominent iris crypts (PIC) and those with absence of iris crypts. The gonio photographs were graded as normal appearing angle or those with angle dysgenesis in the form of a featureless angle, one with a high iris insertion and an angle with prominent iris processes. Using a hierarchical clustering model and a two-way cluster analysis, the distribution of clusters of JOAG was analysed to obtain a classification of JOAG subtypes., Results: The four major clusters identified were: Cluster 1 with NIC and normal angles had the lowest untreated IOP and higher age of onset among all clusters. Cluster 2 with NIC and featureless angle was found to be associated with earliest age of onset. Cluster 3 had NIC and either a high iris insertion or prominent iris processes. Cluster 4 was a heterogeneous cluster with maximum number of patients in a group comprising of those with PIC and high iris insertion., Conclusions: Cluster analysis extracted four subgroups of the JOAG phenotype that have clinical and prognostic significance and can potentially be helpful while evaluating these patients in the clinics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)