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The laboratory-scale (in-vitro) microbial fermentation based on screening of process parameters (factors) and statistical validation of parameters (responses) using regression analysis. The recent trends have shifted from full factorial design towards more complex response surface methodology designs such as Box-Behnken design, Central Composite design. Apart from the optimisation methodologies, the listed designs are not flexible enough in deducing properties of parameters in terms of class variables. Machine learning algorithms have unique visualisations for the dataset presented with appropriate learning algorithms. The classification algorithms cannot be applied on all datasets and selection of classifier is essential in this regard. To resolve this issue, factor-response relationship needs to be evaluated as dataset and subsequent preprocessing could lead to appropriate results. The aim of the current study was to investigate the data-mining accuracy on the dataset developed using in-vitro pyruvate production using organic sources for the first time. The attributes were subjected to comparative classification on various classifiers and based on accuracy, multilayer perceptron (neural network algorithm) was selected as classifier. As per the results, the model showed significant results for prediction of classes and a good fit. The learning curve developed also showed the datasets converging and were linearly separable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pant, Pant. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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.

For decades, dermal tissue grafts have been used in various regenerative, reconstructive, and augmentative procedures across the body. To eliminate antigenicity and immunogenic response while still preserving the individual components and collective structural integrity of the extracellular matrix (ECM), dermis can be decellularized. Acellular dermal matrix (ADM) products like such are produced to accurately serve diverse clinical purposes. The aim of the present study is to evaluate the efficacy of a novel decellularization protocol of the human dermis, which eliminates residual human genetic material without compromising the biomechanical integrity and collagenous content of the tissue. Moreover, a freeze-drying protocol was validated. The results showed that though our decellularization protocol, human dermis can be decellularized obtaining a biocompatible matrix. The procedure is completely realized in GMP aseptic condition, avoiding tissue terminal sterilization., (© 2024. The Author(s).)

In recent days, biogenic and green approaches for synthesizing nanostructures have gained much attention in biological and biomedical applications. Endophytic fungi have been recognized to produce several important biomolecules for use in various fields. The present work describes the use of endophytic fungi isolated from Berberis aristata for the synthesis of multi-twinned silver nanoparticles (MT-AgNPs) and their successful applications in antimicrobial and antimalarial studies. TEM images reveal the formation of multi-twined structures in the synthesized silver nanoparticles. The synthesized MT-AgNPs have shown excellent antibacterial activities against five opportunistic bacteria, viz. Bacillus subtilis (MTCC 441), Pseudomonas aeruginosa (MTCC 424), Escherichia coli (MTCC 443), Klebsiella pneumonia (MTCC 3384), and Aeromonas salmonicida (MTCC 1522). The synthesized MT-AgNPs also exhibit interesting antimalarial activities against Plasmodium falciparum parasites (3D7 strain) by displaying 100% inhibition at a concentration of 1 μg mL -1 against the malaria parasite P. falciparum 3D7. Overall, the results describe a green method for the production of twinned-structured nanoparticles and their potential to be applied in the biomedical, pharmaceutical, food preservation, and packaging industries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The current study reports the synthesis of sustainable nano-hydroxyapatite (nHAp) using a wet chemical precipitation approach. The materials used in the green synthesis of nHAp were obtained from environmental biowastes such as HAp from eggshells and pectin from banana peels. The physicochemical characterization of obtained nHAp was carried out using different techniques. For instance, X-ray diffractometer (XRD) and FTIR spectroscopy were used to study the crystallinity and synthesis of nHAp respectively. In addition, the morphology and elemental composition of nHAP were studied using FESEM equipped with EDX. HRTEM showed the internal structure of nHAP and calculated its grain size which was 64 nm. Furthermore, the prepared nHAp was explored for its antibacterial and antibiofilm activity which has received less attention previously. The obtained results showed the potential of pectin-bound nHAp as an antibacterial agent for various biomedical and healthcare applications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microplastics are ubiquitous environmental pollutants with the potential for adverse impacts on ecosystems and human health. These particles originate from the fragmentation of larger plastic items, shedding from synthetic fibers, tire abrasions, and direct release from personal care products and industrial processes. Once released into the environment, microplastics can disrupt ecosystems, accumulate in organisms, cause physical harm, and carry chemical pollutants that pose risks to both wildlife and human health. There is an urgent need to comprehensively explore the multifaceted issue of microplastic pollution and understand microbial degradation to reduce environmental pollution caused by microplastics. This paper presents a comprehensive exploration of microplastics, including their types, composition, advantages, and disadvantages, as well as the journey and evolution of microplastic pollution. The impact of microplastics on the microbiome and microbial communities is elucidated, highlighting the intricate interactions between microplastics and microbial ecosystems. Furthermore, the microbial degradation of microplastics is discussed, including the identification, characterization, and culturing methods of microplastic-degrading microorganisms. Mechanisms of microplastic degradation and the involvement of microbial enzymes are elucidated to shed light on potential biotechnological applications. Strategies for reducing microplastic pollution are presented, encompassing policy recommendations and the importance of enhanced waste management practices. Finally, the paper addresses future challenges and prospects in the field, emphasizing the need for international collaboration, research advancements, and public engagement. Overall, this study underscores the urgent need for concerted efforts to mitigate microplastic pollution and offers valuable insights for researchers, policymakers, and stakeholders involved in environmental preservation., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The focus of this paper revolves around the examination of flow of ternary hybrid nanofluid, specifically the Al 2 O 3 -Cu-CNT /water mixture, with buoyancy effect, across three distinct geometries: a wedge, a flat plate, and a cone. The study takes into account the presence of quadratic thermal radiation and heat source/sink of non-uniform nature. To develop the model, the Cattaneo-Christov theory is utilized. The equations governing the flow are solved by applying similarity transformations and employing the "bvp4c function in MATLAB" for numerical analysis and solution. Conventional methods for conducting parametric studies often face challenges in producing significant conclusions owing to the inherent complex form of the model and the method involved. To address the aforementioned issue, this paper explores the potential of machine learning methods to foresee the conduct of the flow characterized by multiple interconnected parameters. By utilizing simulated data, an artificial neural network is trained using the Levenberg-Marquardt algorithm to learn and comprehend the underlying patterns. Subsequently, the trained neural network is employed to estimate the Nusselt number on the surfaces of all three geometries. This approach offers a promising alternative to traditional parametric studies, enabling more precise predictions and insights into the behavior of complex systems. The Nusselt number is highest for THNF flow over the cone. The mean squared error (MSE) values for the ANN algorithm, across all analyzed cases, range from 0 to 0.03972 . The findings contribute to an improved understanding of the characteristics and dynamics of ternary hybrid nanofluid flow in various geometries, assisting in the design and optimization of heat transfer systems involving such fluids., 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., (© 2023 The Authors.)

Malaria predominantly affects millions annually in the African and Asian tropical and subtropical countries. With no effective vaccine, malaria prevention is exclusively dependent on preventing human-vector interaction. Anopheles gambiae , the main vector of the malaria parasite Plasmodium falciparum contains Odorant Binding proteins (OBPs) which are considered an attractive drug target for anti-malarial therapy. To identify a potential anti-malarial compound, we performed a structure-based screening of 876 phytocompounds derived from essential oils against the OBP4 by molecular docking. The compounds having better docking scores were assessed for drug-likeness, toxicity, and molecular interaction analysis. As per the results, strong affinities and high stability were demonstrated by two phytocompounds viz. Alpha-cyperone (-8.1 kcal mol -1 ) and Humulene oxide (-8.1 kcal mol -1 ) with OBP4. The hydrophobic interactions involve Phe123, Ala106, Thr57, Ala52, Thr69, and Ile64 within the binding cavities, which may block the OBP4 receptor resulting in disorientation. After that, the potential compounds were subjected to molecular dynamics (MD) simulation to evaluate their structural stability and dynamics at the active site of OBP4. The MM-PBSA result revealed that Alpha-cyperone and Humulene oxide had binding free energy of -92.44 kJ mol -1 and -113.25 kJ mol -1 , respectively. Simulation outcomes demonstrate that these phytocompounds displayed considerable significant structural and pharmacological properties. The LD50 value of Alpha-cyperone and Humulene oxide also suggested that both are safe and suitable for use in natural repellent development. We suggest that the use of these compounds can minimize the treatment period and the various side effects associated with the currently available anti-malarial drugs.Communicated by Ramaswamy H. Sarma.

Traditionally, rice leaf disease identification relies on a visual examination of abnormalities or an analytical result obtained by growing bacteria in the research lab. This method of visual evaluation is qualitative and error-prone. On the other hand, an artificial neural network system is fast and more accurate. Several pieces of research using traditional machine learning and deep convolution neural networks (CNN) have been utilized to overcome the issues. Still, these methods need more semantic contextual global and local feature extraction. Due to this, efficiency is less. Hence, in the present study, a multi-scale feature fusion-based RDTNet has been designed. The RDTNet contains two modules, and the first module extracts feature via three scales from the local binary pattern (LBP), gray, and a histogram of orient gradient (HOG) image. The second module extracts semantic global and local features through the transformer and convolution block. Furthermore, the computing cost is reduced by dividing the query into two parts and feeding them to convolution and the transformer block. The results indicate that the proposed method has a very high average precision, f1-score, and accuracy of 99.55%, 99.54%, and 99.53%, respectively. It is suggestive of improved classification accuracy using multi-scale features and the transformer. The model has also been validated on other datasets confirming that the present model can be used for real-time rice disease diagnosis. In the future, such models can be used for monitoring other crops, including wheat, tomato, and potato., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Valproic acid (VA) is a proven inhibitor of human histone deacetylases (HDACs). The homogenous HDAC has been associated with all major human parasitic pathogens and hence, it has been considered an attractive drug target for anti-leishmanial therapy. To assist in drug design endeavors for HDACs, an in- vitro study has been presented to investigate the VA inhibition on Leishmania donovani HDAC ( Ld HDAC). The regression analysis of VA by 24 hrs viability assay confirmed its activity against Ld HDAC. Moreover, the toxicity of VA is also well documented. Thus, the in-silico experiments were also conducted to screen the non-toxic VA derivatives as anti-leishmanial drug candidates having potential as inhibitors of Ld HDAC. For in-silico study, the 3D structure of target Ld HDAC was developed by homology modeling. Based on their in-silico activity, we shortlisted 13 VA derivatives having maximum affinity for Ld HDAC and identified four potential derivatives that can specifically bind to this protein. After that, these ligands were subjected to molecular dynamics simulation. These derivatives may be effective against L. donovani promastigotes since they followed Lipinski's RO5 and were non-toxic. Thus, screened derivatives can be considered as lead ligands for targeting Ld HDAC and may be used as possible drug candidates to treat leishmaniasis and overcome the limitation of anti-leishmanial drugs. This is the first report of antileishmanial potential of VA and its derivatives targeting Ld HDAC. Hence, the current investigation presents a search for novel target specific drugs to aid the anti-leishmanial drug development.Communicated by Ramaswamy H. Sarma.

Magnetic nanoparticles (MNPs) have captivated the scientific community towards biomedical applications owing to their numerous distinctive physio-chemical properties. In this work, cobalt ferrite (CFNPs) and iron oxide nanoparticles (IONPs) were synthesized using the thermal decomposition method and then functionalized with polyacrylic acid (PAA) for aqueous dispersion. Associated techniques, namely TEM, FESEM, DLS, XRD, and VSM, were used to characterize the synthesized nanoparticles. We also investigated the light-induced and magnetic-field-induced hyperthermia properties of the PAA-functionalized MNPs. It was found that the PAA-CFNPs show a high specific absorption rate (SAR) compared with the PAA-IONPs. Since blood plasma is essential for the delivery and targeting of drugs, studying biological interactions is crucial for effective therapeutic use. Therefore, we performed physical and in silico studies to probe into the mechanistic interaction of CFNPs and IONPs with human hemoglobin. From these studies, we inferred the successful binding between the nanoparticles and protein. Preliminary in vitro cytocompatibility and photothermal toxicity studies in breast cancer (MCF-7) cells treated with the nanoparticles revealed a low dark toxicity and significant laser-induced photothermal toxicity.

Bio-inspired quantum dots have received widespread attention in recent years due to their great potential for biological applications. Herein, we report a one pot hydrothermal synthesis of nitrogen-phosphorus-sulphur (NPS)-codoped carbon quantum dots from endophytic bacteria without using any additional doping precursor. The synthesized CQDs were thoroughly characterized and interestingly found to have a graphene like structure. The synthesized CQDs were then utilized in bactericidal activities against Gram-negative bacteria like Salmonella typhi , Pseudomonas aeruginosa and Gram-positive bacteria like the Bacillus subtilis strain. The strains were treated with different concentrations ranging from 5-100 µg ml -1 . The 5 µg ml -1 concentration appeared to be the MIC (minimum inhibitory concentration) and 100 µg ml -1 is the MBC (minimum bactericidal concentration) maintaining a short incubation period of one hour. A simple, cost-effective and eco-friendly approach to synthesize multi-elemental doped CQDs would certainly cause the method to be used in future for diverse biological applications. As compared to the broadly used antibiotics, the developed CQDs have some added advantages including lower cytotoxicity, excellent photo-stability and high selectivity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The outbreak of COVID-19, a little more than 2 years ago, drastically affected all segments of society throughout the world. While at one end, the microbiologists, virologists, and medical practitioners were trying to find the cure for the infection; the Governments were laying emphasis on precautionary measures like lockdowns to lower the spread of the virus. This pandemic is perhaps also the first one of its kind in history that has research articles in all possible areas as like: medicine, sociology, psychology, supply chain management, mathematical modeling, etc. A lot of work is still continuing in this area, which is very important also for better preparedness if such a situation arises in future. The objective of the present study is to build a research support tool that will help the researchers swiftly identify the relevant literature on a specific field or topic regarding COVID-19 through a hierarchical classification system. The three main tasks done during this study are data preparation, data annotation and text data classification through bi-directional long short-term memory (bi-LSTM)., 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., (Copyright © 2023 Tiwari, Bhattacharjee, Pant, Srivastava and Snasel.)

The standard primitives of quantum computing include deterministic unitary entangling gates, which are not natural operations in many systems including photonics. Here, we present fusion-based quantum computation, a model for fault tolerant quantum computing constructed from physical primitives readily accessible in photonic systems. These are entangling measurements, called fusions, which are performed on the qubits of small constant sized entangled resource states. Probabilistic photonic gates as well as errors are directly dealt with by the quantum error correction protocol. We show that this computational model can achieve a higher threshold than schemes reported in literature. We present a ballistic scheme which can tolerate a 10.4% probability of suffering photon loss in each fusion, which corresponds to a 2.7% probability of loss of each individual photon. The architecture is also highly modular and has reduced classical processing requirements compared to previous photonic quantum computing architectures., (© 2023. The Author(s).)

Moringa oleifera , also known as the "tree of life" or "miracle tree," is classified as an important herbal plant due to its immense medicinal and non-medicinal benefits. Traditionally, the plant is used to cure wounds, pain, ulcers, liver disease, heart disease, cancer, and inflammation. This review aims to compile an analysis of worldwide research, pharmacological activities, phytochemical, toxicological, and ethnomedicinal updates of Moringa oleifera and also provide insight into its commercial and phytopharmaceutical applications with a motive to help further research. The scientific information on this plant was obtained from various sites and search engines such as Scopus, Pub Med, Science Direct, BMC, Google Scholar, and other scientific databases. Articles available in the English language have only been referred for review. The pharmacological studies confirm the hepatoprotective, cardioprotective, and anti-inflammatory potential of the extracts from the various plant parts. It was found that bioactive constituents are present in every part of the plant. So far, more than one hundred compounds from different parts of Moringa oleifera have been characterized, including alkaloids, flavonoids, anthraquinones, vitamins, glycosides, and terpenes. In addition, novel isolates such as muramoside A&B and niazimin A&B have been identified in the plant and have potent antioxidant, anticancer, antihypertensive, hepatoprotective, and nutritional effects. The traditional and nontraditional use of Moringa, its pharmacological effects and their phytopharmaceutical formulations, clinical studies, toxicity profile, and various other uses are recognized in the present review. However, several traditional uses have yet to be scientifically explored. Therefore, further studies are proposed to explore the mechanistic approach of the plant to identify and isolate active or synergistic compounds behind its therapeutic potential.

Biofouling of ship hulls form a vector for the introduction of non-indigenous organisms worldwide. Through increasing friction, the organisms attached to ships' hulls increase the fuel consumption, leading to both higher fuel costs and air emissions. At the same time, ship biofouling management causes both ecological risks and monetary costs. All these aspects should be considered case-specifically in the search of sustainable management strategies. Applying Bayesian networks, we developed a multi-criteria decision analysis model to compare biofouling management strategies in the Baltic Sea, given the characteristics of a ship, its operating profile and operational environment, considering the comprehensive environmental impact and the monetary costs. The model is demonstrated for three scenarios (SC1-3) and sub-scenarios (A-C), comparing the alternative biofouling management strategies in relation to NIS (non-indigenous species) introduction risk, eco-toxicological risk due to biocidal coating, carbon dioxide emissions and costs related to fuel consumption, in-water cleaning and hull coating. The scenarios demonstrate that by the careful consideration of the hull fouling management strategy, both money and environment can be saved. We suggest biocidal-free coating with a regular in-water cleaning using a capture system is generally the lowest-risk option. The best biocidal-free coating type and the optimal in-water cleaning interval should be evaluated case-specifically, though. In some cases, however, biocidal coating remains a justifiable option., 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.)

This research effort aims to evaluate the hazardous potential of the redox state (OH - ) of zero-valent iron nanoparticles (nZVI) and its histopathological and oxidative stress toward Mozambique tilapia, Oreochromis mossambicus . X-ray powder diffraction (XRD) validated the nZVI nanoparticles' chemical composition, while transmission electron microscopy (TEM) revealed that their physical form is round and oval. The exposure to 10 g/mL of nZVI induced the activation of the cellular superoxide dismutase (SOD) activity. Dose-dependent testing of O. mossambicus had a reduction in SOD and an increase in malondialdehyde (MDA) levels, suggesting that nZVI caused oxidative damage. At a concentration of 100 g/mL, the catalase (CAT) and peroxidase (POD) activities of diverse tissues exhibited a gradual decrease after 2 days of exposure and a fast increase until day 6. The scavenging of reactive oxygen species (ROS) in the epidermis, liver, and gills of O. mossambicus deteriorated and accumulated gradually. MDA levels in the skin, gill, and liver tissues were substantially higher after 8 days of exposure to 100 and 200 g/mL nZVI compared to those of the control group and those exposed to 10 and 50 g/mL nZVI for 2 days. Extreme histological and morphological abnormalities were seen in the skin, gill, and liver tissues of experimental animals, demonstrating that the damage resulted from direct contact with nZVI in water. A one-way ANOVA followed by Dunnett's post-test was performed to investigate significant differences., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Deployment of secured healthcare information is a major challenge in a web-based environment. eHealth services are subjected to same security threats as other services. The purpose of blockchain is to provide a structure and security to the organization data. Healthcare data deals with confidential information. The medical records can be well organized and empower their propagation in a secured manner through the usage of blockchain technology. The study throws light on providing security of health services through blockchain technology. The authors have analyzed the various aspects of role of blockchain in healthcare through an extensive literature review. The application of blockchain in COVID-19 has also been analyzed and discussed in the study. Further application of blockchain in Indian healthcare has been highlighted in the paper. The study provides suggestions for strengthening the healthcare system by blending machine learning, artificial intelligence, big data, and IoT with blockchain., Competing Interests: There is no conflict of interest in this research., (Copyright © 2022 Shilpa Srivastava et al.)

Introduction: Home parenteral nutrition (HPN) is essential for patients with intestinal failure requiring long-term nutritional support. The Amerita Quality Improvement Project for HPN Patients (QIP-PN) explored the effect of a physician nutrition expert (PNE)-led multidisciplinary nutritional support team (MNST) on HPN care for patients under its service., Objective: To determine an MNST effect on adherence to protocols, outcomes and quality of life (QOL) in HPN., Methods: The study was divided into three phases: data review (phases 1a and 1b), observation (phase 2) and intervention (phase 3). Seven Amerita locations were selected as 'study branches' (population), from which all study patients and controls were drawn. The quality improvement project employed a quasi-experimental case-matched control group (control) design. Data were collected on demographics, treating physicians PNE status, HPN care variables, recommended interventions, quality-of-life assessment, adverse outcomes and hospitalisations. Paired t-test compared continuous data between phases 2 and 3. Comparisons between study and control groups used a negative binomial regression model., Results: Thirty-four patients were reviewed in phase 1a and 197 in phase 1b. Forty study patients completed phase 2 and progressed into phase 3, of whom 30 completed ≥60 therapy days. Patients were lost to follow-up if they discontinued HPN for any reason. Improvements in weight, body mass index and QOL were seen in the study patients during intervention. Recommendations made and accepted by treating physicians differed based on PNE status. Study patients had fewer adverse outcomes and related hospitalisations than controls., Conclusion: MNST recommendations improved clinical, biochemical parameters and patients' self-reported overall health. MNST input reduced adverse outcomes, hospitalisation and the length of stay at the hospital. This study highlights the potential for MNST to have a significant impact on the quality and overall cost of HPN management., Competing Interests: Competing interests: MR and MS are paid consultants for Amerita. RB, JH, FG, AT, DS, AD and DR are paid employees of Amerita. MP, VP, KS and NA have no conflicts., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Assessing the interaction between microbes and nanocatalysts for finding an inclusive, proactive and deep understanding of nanoparticles-based toxicity is vital for discovering their broad range of applications. Palladium based photocatalysts owing to their unique fundamental characteristics and brilliant physicochemical potential have gained immense interest in environment remediation as disinfection system. In the present study, we report synthesis of a novel palladium nanoparticles decorated bismuth oxybromide (Pd/BiOBr) nanostructures using an energy efficient solution-based method, having excellent photocatalytic antibacterial action. The synthesized nanomaterials was thoroughly characterized using various analytical techniques. The photocatalytic antibacterial efficiency of Pd/BiOBr was evaluated against some common pathogenic strains of Gram-positive and Gram-negative bacteria (Pseudomonas fluorescens, Pseudomonas aeruginosa, Escherichia coli, Aeromonas salmonicida, Salmonella typhimurium, Klebsiella pneumoniae, Bacillus subtilis). In our results Pd/BiOBr showed excellent photocatalytic disinfection efficacy with > 99.9% bacterial inactivation. A very low concentration of Pd/BiOBr (0.5 µg/mL) effectively inhibited the bacterial growth in response to just 2 h of visible light irradiation, while 1 µg/mL of Pd/BiOBr completely killed all the tested bacterial strains proving their magnificent bactericidal potential. The developed materials with exceptional antibacterial broad range efficiency can be used in different photocatalytic disinfection systems including water purification systems, biofilm exclusion and combating differential antibiotic resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Due to the continuous depletion of natural resources currently used for electricity generation, it is imperative to develop alternative energy sources. Human waste is nowadays being explored as an efficient source to produce bio-energy. Human waste is renewable and can be used as a source for an uninterrupted energy supply in bioelectricity or biofuel. Annually, human waste such as urine is produced in trillions of liters globally. Hence, utilizing the waste to produce bioenergy is bio-economically suitable and ecologically balanced. Microbial fuel cells (MFCs) play a crucial role in providing an effective mode of bioelectricity production by implementing the role of transducers. MFCs convert organic matter into energy using bio-electro-oxidation of material to produce electricity. Over the years, MFCs have been explored prominently in various fields to find a backup for providing bioenergy and biofuel. MFCs involve the role of exoelectrogens which work as transducers to convert the material into electricity by catalyzing redox reactions. This review paper demonstrates how human waste is useful for producing electricity and how this innovation would be beneficial in the long term, considering the current scenario of increasing demand for the supply of products and shortages of natural resources used to produce biofuel and bioelectricity.

Over the past few years, we are witnessing the advent of a revolutionary bioengineering technology in biochar production and its application in waste treatment and an important component in power generation devices. Biochar is a solid product, highly rich in carbon, whose adsorption properties are ideal for wastewater decontamination. Due to its high specific surface area to volume ratio, it can be utilized for many environmental applications. It has diverse applications in various fields. This review focuses on its various applications in wastewater treatment to remove various pollutants such as heavy metals, dyes, organic compounds, and pesticides. This review also highlights several energy-based applications in batteries, supercapacitors, and microbial fuel cells. It described information about the different feedstock materials to produce LB-derived biochar, the various conditions for the production process, i.e., pyrolysis and the modification methods of biochar for improving properties required for wastewater treatment. The present review helps the readers understand the importance of biochar in wastewater treatment and its application in power generation in terms of batteries, supercapacitors, microbial fuel cells, applications in fuel production, pollutant and dye removal, particularly the latest development on using LB-derived biochar. This review also highlights the economic and environmental sustainability along with the commercialization of biochar plants. It also describes various pyrolytic reactors utilized for biochar production., 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. Published by Elsevier B.V.)

The RNA-dependent RNA polymerase (RdRp) is one of the crucial enzymes in severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) catalysing the replication of RNA, therefore acts as a potential target for antiviral drug design. The fixation of a ligand in the active site of RdRp may alter the SARS-CoV-2 life cycle. Present work aimed at identifying novel inhibitors of the SARS-CoV-2 RdRp enzyme by performing pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation (MDS). Initially, the pharmacophore model of SARS-CoV-2 RdRp was constructed and the resulting model was used to screen compounds from ChEMBL, ZINC and PubChem databases. During the investigation, 180 compounds were screened using the above model and subjected to molecular docking with RdRp. Two compounds viz. ChEMBL1276156 and PubChem135548348 showed a strong binding affinity with RdRp than its standard inhibitor, Remdesivir. Toxicity prediction of these two compounds reveals their non-toxic nature. These compounds were further subjected to MDS for 100 ns to check their stability after binding with RdRp. The MDS of RdRp-ChEMBL1276156 and RdRp-PubChem135548348 complexes show enhanced stability in comparison to the RdRp-Remdesivir complex. The average interaction energy calculated after 100 ns of MDS was -146.56 and -172.68 KJ mol -1 for RdRp-CHEMBL1276156 complex and RdRp-PubChem135548348 complex, respectively, while -59.90 KJ mol -1 for RdRp-Remdesivir complex. The current investigation reveals that these two compounds are potent inhibitors of SARS-CoV-2 RdRp and they could be tested in the experimental condition to evaluate their efficacy against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

DEA, incepted in 80s, has emerged as a popular decision-making technique, for determining the efficiency of similar units. Due to its simplicity and applicability, DEA has gained the attention of scientists and researchers working in diverse areas, which has contributed towards a rich literature both in terms of theoretical development as well as different applications. This paper tries to bring together the near 40 years of existence of DEA in a concise format by discussing the popular DEA models, their advantages and shortcomings, and different applications of DEA. It also provides a brief bibliometric analysis to highlight the development of DEA over the years in terms of publication trends, highly cited papers, journal citation, etc., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding authors states that there is no conflict of interest., (© The Author(s) under exclusive licence to International Center for Numerical Methods in Engineering (CIMNE) 2022.)

Following photopigment bleaching, the rhodopsin and cone-opsins show a characteristic exponential regeneration in the dark with a photocycle dependent on the retinal pigment epithelium. Melanopsin pigment regeneration in animal models requires different pathways to rods and cones. To quantify melanopsin-mediated light adaptation in humans, we first estimated its photopigment regeneration kinetics through the photo-bleach recovery of the intrinsic melanopsin pupil light response (PLR). An intense broadband light (~120,000 Td) bleached 43% of melanopsin compared to 86% of the cone-opsins. Recovery from a 43% bleach was 3.4X slower for the melanopsin than cone-opsin. Post-bleach melanopsin regeneration followed an exponential growth with a 2.5 min time-constant (τ) that required 11.2 min for complete recovery; the half-bleaching level (I p ) was ~ 4.47 log melanopic Td (16.10 log melanopsin effective photons.cm -2 .s -1 ; 8.25 log photoisomerisations.photoreceptor -1 .s -1 ). The effect on the cone-directed PLR of the level of the melanopsin excitation during continuous light adaptation was then determined. We observed that cone-directed pupil constriction amplitudes increased by ~ 10% when adapting lights had a higher melanopic excitation but the same mean photometric luminance. Our findings suggest that melanopsin light adaptation enhances cone signalling along the non-visual retina-brain axis. Parameters τ and I p will allow estimation of the level of melanopsin bleaching in any light units; the data have implications for quantifying the relative contributions of putative melanopsin pathways to regulate the post-bleach photopigment regeneration and adaptation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The multifaceted nature of the renin-angiotensin system (RAS) makes it versatile due to its involvement in pathogenesis of the cardiovascular disease. Angiotensin II (Ang II), a multifaceted member of RAS family is known to have various potential effects. The knowledge of this peptide has immensely ameliorated after meticulous research for decades. Several studies have evidenced angiotensin I receptor (AT 1 R) to mediate the majority Ang II-regulated functions in the system. Functional crosstalk between AT 1 R mediated signal transduction cascades and other signaling pathways has been recognized. The review will provide an up-to-date information and recent discoveries involved in Ang II receptor signal transduction and their functional significance in the cardiovascular system for potential translation in therapeutics. Moreover, the review also focuses on the role of stem cell-based therapies in the cardiovascular system., 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., (Copyright © 2021 Verma, Pant, Paliwal, Dwivedi and Sharma.)

Sarcolipin (SLN) is a regulator of sarco/endo plasmic reticulum Ca 2+ -ATPase (SERCA) pump and has been shown to be involved in muscle nonshivering thermogenesis (NST) and energy metabolism. Interestingly, SLN expression is significantly upregulated both during muscle development and in several disease states. However, the significance of altered SLN expression in muscle patho-physiology is not completely understood. We have previously shown that transgenic over-expression of SLN in skeletal muscle is not detrimental, and can promote oxidative metabolism and exercise capacity. In contrast, some studies have suggested that SLN upregulation in disease states is deleterious for muscle function and ablation of SLN can be beneficial. In this perspective article, we critically examine both published and some new data to determine the relevance of SLN expression to disease pathology. The new data presented in this paper show that SLN levels are induced in muscle during systemic bacterial ( Salmonella ) infection or lipopolysaccharides (LPS) treatment. We also present data showing that SLN expression is significantly upregulated in different types of muscular dystrophies including myotubular myopathy. These data taken together reveal that upregulation of SLN expression in muscle disease is progressive and increases with severity. Therefore, we suggest that increased SLN expression should not be viewed as the cause of the disease; rather, it is a compensatory response to meet the higher energy demand of the muscle. We interpret that higher SLN/SERCA ratio positively modulate cytosolic Ca 2+ signaling pathways to promote mitochondrial biogenesis and oxidative metabolism to meet higher energy demand in muscle., 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., (Copyright © 2021 Bal, Gupta, Pant, Sopariwala, Gonzalez-Escobedo, Turner, Gunn, Pierson, Harper, Rafael-Fortney and Periasamy.)

Background: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status., Methods: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed., Results: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error., Conclusion: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The new outbreak of the corona virus (Covid-19) is expanding rapidly worldwide, disrupting millions and prompting authorities to take swift measures to avoid the disease. National lockdown imposed by the Indian government since 25 March 2020, the early lockdown action shows as compared to many other Countries/states can benefit from limiting the final size of the epidemic. A report on the issue of spreading the Covid-19 modeling in India is under review. This study analyzes Covid-19 infections by 20Dec 2021 and presents a mathematical approach for forecasting new cases or cumulative cases in practical situations. This forecast is much needed to schedule/continue medical set-ups for possible action to tackle the Covid-19 outbreak. It is important to mention here that the number of authors has proposed different models for predicting the expansion of Covid-19 to India and other countries; almost no model has yet to be demonstrated viable. With this mathematical model, it is simple to forecast the transfer of Covid-19. It is clear from the data that lockdown has played a significant role in controlling the transmission of the disease. A close match between the predicted empirical results and the available results proves the derived model similarity., 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 Elsevier Ltd. All rights reserved. Selection and peer-review under responsibility of the scientific committee of the 3rd International Conference on Computational and Experimental Methods in Mechanical Engineering.)

Given the severity of injuries to biota in coastal wetlands from the Deepwater Horizon oil spill (DWH) and the resulting availability of funding for restoration, information on impacted salt marshes and biotic development of restored marshes may both help inform marsh restoration planning in the near term and for future spills. Accordingly, we performed a meta-analysis to model a restoration trajectory of total macroinfauna density in constructed marshes (studied for ~30 y), and with a previously published restoration trajectory for amphipods, we compared these to recovery curves for total macroinfauna and amphipods from DWH impacted marshes (over 8.5 y). Total macroinfauna and amphipod densities in constructed marshes did not consistently reach equivalency with reference sites before 20 y, yet in heavily oiled marshes recovery occurred by 4.5 y post spill (although it is unlikely that macroinfaunal community composition fully recovered). These differences were probably due to initial conditions (e.g., higher initial levels of belowground organic matter in oiled marshes) that were more conducive to recovery as compared to constructed marshes. Furthermore, we found that amphipod trajectories were distinctly different in constructed and oiled marshes as densities at oiled sites exceeded that of reference sites by as much as 20x during much of the recovery period. Amphipods may have responded to the rapid increase and high biomass of benthic microalgae following the spill. These results indicate that biotic responses after an oil spill may be quantitatively different than those following restoration, even for heavily oiled marshes that were initially denuded of vegetation. Our dual trajectories for oil spill recovery and restoration development for macroinfauna should help guide restoration planning and assessment following the DWH as well as for restoration scaling for future spills., 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 © 2020 Elsevier Ltd. All rights reserved.)

Purpose of Review: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is identified from Wuhan, China, and has spread almost worldwide. Recently, the newly identified SARS-CoV-2 has been confirmed to kill millions of people worldwide and is dangerous to society health, survival, and livelihood. The people with cardiovascular problems are noticed as most common patients of coronavirus disease 2019 (COVID-19). There is a greater risk of mortality and morbidity in these patients than other patients of COVID-19. In the heart, expressed angiotensin-converting enzyme 2 (ACE2) and response effect of hyperactivity with angiotensin II associated to the renin-angiotensin mechanism are key factors of hypertension, atherosclerosis, and congestive heart failure., Recent Findings: Mortality rates have been observed about 10.5% cases in patients with cardiovascular disease; however, a mortality rate of 52% was recorded in patients with heart failure, while 12% recovered ultimately. The occupancy of intense injury controlled by troponin elevation was a noteworthy factor in relation to mortality. Among 187 patients infected with SARS-CoV-2, about 35% were diagnosed with cardiovascular disease (CVD) history and 28% with raised troponin. Troponin elevation was identified more frequently (55%) in patients with cardiovascular diseases. Mortality rate in patients without cardiovascular diseases and normal troponin was 7.6%, normal troponin and cardiovascular disease with 13.3%, augmented troponin and without cardiovascular disease 37.5%, however 69.4% among cardiovascular disease and advanced troponin., Summary: The study reflected a significant association of case fatality rate (CFR) to COVID-19 patients with cardiovascular diseases which supposed to be the most common dangerous risk factor and health challenge during the current pandemic situation., Competing Interests: Conflict of InterestNone, (© Springer Nature Switzerland AG 2020.)

Participatory modelling increases the transparency of environmental planning and management processes and enhances the mutual understanding among different parties. We present a sequential probabilistic approach to involve stakeholders' views in the formal decision support process. A continuous Bayesian Belief Network (BBN) model is used to estimate population parameters for stakeholder groups, based on samples of individual value judgements. The approach allows quantification and visualization of the variability in views among and within stakeholder groups. Discrete BBN is populated with these parameters, to summarize and visualize the information and to link it to a larger decision analytic influence diagram (ID). As part of ID, the resulting discrete BBN element serves as a distribution-form decision criteria in probabilistic evaluation of alternative management strategies, to help find a solution that represents the optimal compromise in the presence of potentially conflicting objectives. We demonstrate our idea using example data from the field of marine spatial planning. However, this approach is applicable to many types of management cases. We suggest that by advancing the mutual understanding and concrete participation this approach can further facilitate the stakeholder involvement also during the various stages of the environmental management process., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Pancreatic serous cystadenoma (SCA) is a benign neoplastic lesion with a distinctive gross and microscopic appearance consisting of numerous thin-walled cysts lined by uniform epithelial cells with clear cytoplasm and small nuclei. The vast majority of serous cystadenomas are benign. Pancreatic SCA has rarely been reported in association with other pancreatic lesions. We present a challenging case in which a cystic and solid pancreatic mass was identified on imaging studies. FNA was performed and showed clusters of atypical cells with significant nuclear pleomorphism (>4:1), disorganized, overlapping nuclei, and prominent nucleoli. The FNA diagnosis was positive for malignancy, consistent with adenocarcinoma. The patient underwent neoadjuvant therapy and pancreaticoduodenectomy. Final pathology showed a serous cystadenoma associated with small foci of high-grade PanIN. The lack of invasive adenocarcinoma in the resection specimen was most likely due to complete response of the tumor to neoadjuvant chemoradiation therapy, but it is also possible that only high-grade PanIN was present initially. To our knowledge, this is the first reported case of SCA and high grade PanIN/PDAC that was assessed by FNA. We discuss the cytologic differential diagnosis and how to avoid potential pitfalls highlighted by this case., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite linear-optical fusion (Bell measurement) being probabilistic, photonic cluster states for universal quantum computation can be prepared without feed-forward by fusing small n-photon entangled clusters, if the success probability of each fusion attempt is above a threshold, [Formula: see text]. We prove a general bound [Formula: see text], and develop a conceptual method to construct long-range-connected clusters where [Formula: see text] becomes the bond percolation threshold of a logical graph. This mapping lets us find constructions that require lower fusion success probabilities than currently known, and settle a heretofore open question by showing that a universal cluster state can be created by fusing 3-photon clusters over a 2D lattice with a fusion success probability that is achievable with linear optics and single photons, making this attractive for integrated-photonic realizations.

Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

Merkel cell carcinoma (mcc) is an uncommon malignancy of the skin arising from cells located in the deeper layers of the epidermis called Merkel cells. This malignancy rarely presents as a metastatic disease, and the field is therefore deficient in regards to management. We report the case of a 49-year-old woman who presented with a presumptive diagnosis of osteomyelitis of the left fifth digit that was resistant to treatment with antibiotics; she underwent debridement of the digit that revealed mcc and was later to have metastatic disease to her lungs, liver, and musculoskeletal system. The management of mcc, although simple in the early stage of the disease, can become challenging when it is more advanced. Multiple new modalities for its treatment have emerged over the last few years, and more recently, clinical trials are being conducted for the use of immunotherapy agents in the treatment of this malignancy.

Cholesteryl Ester Storage Disease (CESD), is a rare multisystem autosomal recessive disorder and belongs to the broad family of lysosomal storage disorders. It can present anytime from infancy and childhood to even adulthood. The clinical manifestations are generally severe in infants and with milder forms in adults. One of the prominent sites of involvement is liver. Due to low awareness of this condition among physicians including surgical pathologists, majority of the liver biopsies, especially from the adults are often misdiagnosed as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis or cryptogenic cirrhosis. Given the recent availability of safe and effective enzyme replacement therapy that can alter the natural course of CESD, the pathologists signing out adult and pediatric liver biopsies should be aware of this entity, thus contributing to timely patient management. This review discusses the clinical features, pathogenesis, diagnostic approach, differential diagnosis and management of CESD in adults., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To evaluate dose calculation accuracy of various algorithms in lung equivalent inhomogeneity comprising tumor within it and comparison with Gafchromic film data., Materials and Methods: Gafchromic film measured central axis absorbed dose in lung insert (-700 Hounsfield unit [HU]), in racemosa wood cylindrical inhomogeneity (-725 HU) and at three surfaces of tumor (-20 HU) created in cylindrical inhomogeneity, put in the cavity of computerized imaging reference systems (CIRS) thorax phantom were compared with convolution (CON), superposition (SP), fast SP (FSP), and X-ray voxel Monte Carlo (XVMC) algorithms calculated dose using 6 MV beams of field size 2 cm × 2 cm, 3 cm × 3 cm, 4 cm × 4 cm, 5 cm × 5 cm, and 8 cm × 8 cm., Results: XVMC was in good agreement with film measured results for all selected field sizes except 3 cm × 3 cm. SP under estimated by 5.7% at the center of the lung insert while deviation up to 6% was found at the cent of wood inhomogeneity in 2 cm × 2 cm. Except CON, increase in dose from proximal to the central surface of the tumor and then dose falloff from central to the distal surface for field size 2 cm × 2 cm to 4 cm × 4 cm was recorded. The change in film measured percentage depth dose from 2 cm × 2 cm to 3 cm × 3 cm field sizes was found -8% however for consecutive field size(s) larger than 3 cm × 3 cm this difference was less. CON and FSP produced overestimated results., Conclusion: Out of four algorithms, XVMC found consistent with measured data. The electronic disequilibrium within and at the interface of inhomogeneity make the accurate dose predictions difficult. These limitations results in deviations from the expected results of the treatments.

Aim: The aim of the present study is volumetric analysis of root canal filling with cold lateral compaction, Obtura II, Thermafil, and Calamus using spiral computerized tomography (SCT)., Materials and Methods: Root canals of eighty mandibular premolars were instrumented using rotary ProTaper, and the volume of the canal space was measured using spiral computerized tomography (SCT). The teeth were divided into four groups of twenty teeth each, and root canals filled by lateral compaction technique, Thermafil carriers, Obtura II, and Calamus techniques, respectively. AH Plus was used as a sealer with all techniques. The filled volume in each canal was measured using SCT, and the percentage of obturated volume (POV) was calculated. The data were statistically analyzed using ANOVA, Kruskal-Wallis test, and Mann-Whitney U-test., Results: The four groups were comparable in canal volume. The overall POV was 78.11%, 85.72%, 82.50%, and 87.89% for lateral compaction, Thermafil, Obtura II, and Calamus, respectively (P Conclusion: The greatest POV was obtained with Calamus and Thermafil. Voids were seen in all root fillings.

Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis and heat production, and contributes to temperature homeostasis. SLN also affects whole-body metabolism and weight gain in mice, and is upregulated in various muscle diseases including muscular dystrophy, suggesting a role for SLN during increased metabolic demand. In this review we also highlight the physiological roles of skeletal muscle beyond contraction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Inclusion of inhomogeneity corrections in intensity modulated small fields always makes conformal irradiation of lung tumor very complicated in accurate dose delivery., Objective: In the present study, the performance of five algorithms via Monte Carlo, Pencil Beam, Convolution, Fast Superposition and Superposition were evaluated in lung cancer Intensity Modulated Radiotherapy planning., Materials and Methods: Treatment plans for ten lung cancer patients previously planned on Monte Carlo algorithm were re-planned using same treatment planning indices (gantry angel, rank, power etc.) in other four algorithms., Results: The values of radiotherapy planning parameters such as Mean dose, volume of 95% isodose line, Conformity Index, Homogeneity Index for target, Maximum dose, Mean dose; %Volume receiving 20Gy or more by contralateral lung; % volume receiving 30 Gy or more; % volume receiving 25 Gy or more, Mean dose received by heart; %volume receiving 35Gy or more; %volume receiving 50Gy or more, Mean dose to Easophagous; % Volume receiving 45Gy or more, Maximum dose received by Spinal cord and Total monitor unit, Volume of 50 % isodose lines were recorded for all ten patients. Performance of different algorithms was also evaluated statistically., Conclusion: MC and PB algorithms found better as for tumor coverage, dose distribution homogeneity in Planning Target Volume and minimal dose to organ at risks are concerned. Superposition algorithms found to be better than convolution and fast superposition. In the case of tumors located centrally, it is recommended to use Monte Carlo algorithms for the optimal use of radiotherapy.