More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

It is common knowledge that increasing CO₂ concentration plays a major role in enhancement of the greenhouse effect and contributes to global warming. The purpose of this study is to complement the conventional and established theory that increased CO₂ concentration due to human emissions causes an increase of temperature, by considering the reverse causality. Since increased temperature causes an increase in CO₂ concentration, the relationship of atmospheric CO₂ and temperature may qualify as belonging to the category of “hen-or-egg” problems, where it is not always clear which of two interrelated events is the cause and which the effect. We examine the relationship of global temperature and atmospheric carbon dioxide concentration at the monthly time step, covering the time interval 1980–2019, in which reliable instrumental measurements are available. While both causality directions exist, the results of our study support the hypothesis that the dominant direction is T → CO₂. Changes in CO₂ follow changes in T by about six months on a monthly scale, or about one year on an annual scale. We attempt to interpret this mechanism by involving biochemical reactions, as at higher temperatures soil respiration, and hence CO₂ emission, are increasing.

Despite of being an exceptionally biodiversity rich country, the forest coverage of Bangladesh is declining at an alarming rate. Declaration and management of protected areas in this regard is one of the efforts from government side to tackle the loss of biodiversity. The limited numbers of forest-protected areas (FPA), established to conserve the dwindling forest biodiversity of the country with high pressure on them for timber, non-timber forest products, and fuelwood - makes their management challenging. Moreover, most of the FPAs of the country declared only in the recent decades with very limited infrastructure, manpower and policy support for monitoring and governance. Some people-centred approaches for the management of FPAs and alternative livelihood and income generation subsidies although made available through a few project interventions, their number are still inadequate and performance remains less than satisfactory. This chapter provides a critical review of the FPAs of Bangladesh looking at their role in biodiversity conservation, management challenges, and key lessons from previous management interventions with recommendations for the future. It has been revealed that the FPA system of Bangladesh still poorly represents the diverse forest ecosystems with relatively small forest size and lack of corridors for the movement of wildlife. There are ample opportunities to render co-management of FPAs an effective strategy to minimize the conflicts in FPAs management in the country. It is, however, important to ensure the access of local forest-dependent people to different alternative income generating options that may adequately support their livelihoods.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

Pneumonia caused by a new coronavirus SARS-CoV-2 has caused serious harm to people's lives and health in Wuhan, China. By February 26, 2020, over 80,000 people were infected and 2,814 died from the infection. The initial route of infection is the binding of the spike protein (S protein) of the virus to the angiotensin-converting enzyme 2 (ACE2). From bioinformatics analysis, we found that the S protein of SARS-CoV-2 produced an evolutionary mutation of K403R compared with the S protein of SARS-CoV, forming an adjacent RGD motif at the interaction surface. As the RGD motif is considered as a ligand for many cell surface integrins, we proposed that the binding of S protein of SARS-CoV-2 with integrins may facilitate the infection process of the virus. Therefore, high-throughput virtual screening was performed by choosing the key residues of S protein interface of SARS-CoV-2 and the adjacent RGD motif as potential binding site, to search for the potential agents targeting interaction of S protein of SARS-CoV-2 with both ACE2 and integrins as potential therapeutic drugs. Various libraries including the FDA-approved drugs etc. were screened, and Nadide, Losartan, 9'''-Methyllithospermate B and Leonurine etc. were identified as representative potential drugs candidate for COVID-19.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

Background: On late December 2019, a viral pneumonia known as coronavirus disease 2019 (COVID-19), was originated from China and spread very rapidly in the world. Therefore, COVID-19 became a global concern and health problem. Methods: We presented four patients in this study. They were selected from patients who presented with pneumonia symptoms and were suspicious for COVID-19 and referred to the intended centers for COVID-19 diagnosis and management of Shiraz University of Medical Sciences in the south of Iran. Two nasopharyngeal and oropharyngeal throat swab samples were collected from each patient and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR), and also samples were sent for influenza viruses and all the respiratory panel. Results: In the present report, four patients were diagnosed in the starting days of COVID-19 disease in our center in south of Iran with co-infection of SARS-CoV-2 and influenza virus. Conclusions: This co-infection of COVID-19 and influenza highlights the importance of considering SARS-CoV-2 PCR assay regardless of other positive findings for other pathogens in the primary test during the epidemic.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Good governance in natural resource management (NRM) is one of the most challenging issues in developing countries that often inappropriately embedded in national policies and political agendas. It is, in fact, even more important for countries like Bangladesh with exceptionally high pressure and dependence on its natural resources for sustaining rural livelihoods. Globally, nowadays, good governance is considered as one of the key factor for achieving the goal of sustainable development and biodiversity conservation. Bangladesh, of late has responded to that global zeal by involving local communities in the management of country’s declining forest and other natural resources. The colonial legacy of the forestry sector of Bangladesh was planned and, managed as interim projects through donors’ prescriptions. Thus, institutions, management processes and conservation outcomes were problematic. The conventional approach adopted by colonial and post-colonial regimes for forest management also proved to be inefficient due to its top-down management system. The absolute dependency on donor support, and their prescription sometimes worsened the situation both ecologically and socially. Global, regional and local trends supported the need for a different dimension in the governance paradigms. The introduction of a pluralistic approach, known as co-management in protected areas (PAs) is an example of an attempt whereby shared governance mechanism are implemented to attain the desired goals of conservation that will also address the livelihoods and aspirations of communities living in and around PAs of the country. However, in designing future forest and PA regimes the concern of the external aid support and attached conditions remain a reality that needs to be addressed. Adequate attention should be given to our vanishing biodiversity, culture and community livelihoods through devising an appropriate governance mechanism recognizing and supporting local rights, access and participation in the environmental management. It is now time to mainstream the adhoc nature of governance according to our national conservation strategy and policy frameworks in order to achieve the goals and objectives of the Bangladesh NRM sector addressing the human and community right of people in the specific context of forest protected areas management.

According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

Abstract The COVID-19 pandemic has tremendously affected the African continent and the rest of the world. Most businesses have closed and a lot of people have lost their jobs. The aviation industry has been shaken to the core with airlines losing millions of dollars and flights being cancelled. The tourism industry has consequently been affected due to restricted travel of tourists, impacting wildlife conservation and livelihoods. Schools, colleges and universities have been closed. The virus has infected millions of people and hundreds of thousands of people have died globally putting strain on health systems especially those of hard hit countries. Various countries all over the world have put measures to control the spread of the virus through lockdowns and social distancing policies. The reduced economic activities and mobility of people has resulted in improved air quality, cleaner water and beaches in some countries. However there are also negative impacts such as challenges in waste management, increased pharmaceutical and household waste and discovery of the corona virus in wastewater, a potential threat to public health. A considerable amount of research has been done on the socio-economic impacts of COVID-19 in Africa but there is still limited research on its impact on the environment. This paper serves to highlight the observed and potential environmental impacts of COVID-19 in Africa.

Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Pharmaceutically active compounds and organic pollutants are becoming a major environmental dispute possessing serious threat to the water bodies and terrestrial ecosystem. Microorganisms are capable of the self-purification process, and hence the microbial degradation is considered a lucrative method to counteract the therapeutic and recalcitrant pollutants. Pharmaceutical toxicants in aquatic system can be treated by conventional wastewater treatment, but slow sludge settling, presence of mixture of pharmaceuticals and recalcitrant compounds often pose a potential ecological risk. Some microbial strains are very effective in reducing the chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), and turbidity in pharmaceutical industrial wastewater treatment. The natural microbial community has a significant role in the ecological processes of pharmaceutical and organic compounds, including non-steroidal anti-inflammatory drugs, analgesics, blood lipid regulators and other micropollutants. Specific bacterial isolates can act as biodegraders, and fungal treatment could offer protection to the ecosystem. These microorganisms use the pollutants as their sole carbon source and transform the contaminants by co-metabolic pathways. Natural attenuation by native microorganisms, biostimulation and bioaugmentation are the processes employed to degrade the target contaminant. Microorganisms may also be genetically engineered to improve the neutralization efficiency, which would assist in the mineralization of the pollutants. Thus, employing microorganisms to detoxify the pollutants probably enhances the sustainable potential biodegradability, improves water quality standards and ensures eco-friendly alternative bioremediation strategy.

The corona (COVID-19) pandemic offers an opportunity for dealing with persistent problems, through a transformative recovery process. It is a crisis that offers opportunities for dealing with three interrelated crises: the ecological crisis (climate change, loss of biodiversity, resource depletion, pollution and ecosystem destruction), the confidence crisis (people losing trust in government, politics, companies, regular news channels, science, each other and the future), and the inequality crisis (the widening of the gap between rich and poor). Our argument is that sustainability transitions will not succeed without a different economy and another social contract with the associated rights and duties of care (for the environment and the well-being of others, including future generations). A different social contract is not only desirable from the point of view of sustainability and fairness, justice and equality, but is also necessary to restore citizens' trust in politics, government, companies and each other. In the paper we discuss mechanisms towards a Natural Social Contract, systemic leverage points for system transformations and possibilities for co-evolutionary governance by actor coalitions interested in transformative change. The combination of those three elements helps to synchronize different agendas and reduce the chance that they will work against each other.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, M^pro of the COVID-19 virus. With the high-resolution X-ray crystallography structure of this viral enzyme recently being solved, CADD provides a veritable tool for rapidly screening diverse sets of compounds with the aim of identifying ligands capable of forming energetically favorable complexes with M^pro . From our screening of 1,082,653 compounds derived from the ZINC, the DrugBank, and our in-house African natural product libraries, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective M^pro inhibitors, which include FDA-approved drugs, drug candidates in clinical trials, as well as natural products. The top-ranking compounds are characterized by the presence of an extended ring system combined with functional groups that allow the ligands to adapt flexibly to the M^pro active site as, for example, present in the biflavonoid amentoflavone, one of the most promising compounds identified here. This particular chemical architecture leads to considerable stronger binding than found for reference compounds with in vitro demonstrated M pro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

Introduction The COVID-19 virus was initially reported in Dec 2019 as the causative agent of a pneumonia breakout in Wuhan China. This virus rapidly spread from China to Europe and the East Coast of the United States eventually reaching the South West United States and indigenous tribes in mid -March. Since, then the indigenous tribes have been devasted by the virus which the Governor of New Mexico has likened as an existential threat. Methodology A PubMed search was performed utilizing the words: Navajo Indian, Indigenous Indian, Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal Results: Navajo’s and other indigenous peoples may have elevated levels of ACE2 receptors in their lungs and other tissues allowing greater susceptibility to the COVID-19 virus. Increased levels of diabetes and protein nutrition are directly related to increased morbidity and mortality in this group while obesity, COPD, and heart diseas are not. The increased morbidity and mortality is exasperated by an inability to test for COVID-19 Conclusion: The infectivity rate of Navaho’s on the reservation is 22 times higher than the national average with a death rate near 4%. Comorbidites account for some of the increased morbidity and mortality while lack of access to adequate health care unnecessarily magnifies the poor outcome. The threat to indigenous tribes in the Southwest of COVID-19 is dire.

Cannabis is among the oldest human domesticates and has been subjected to intensive artificial (human-mediated) selection throughout history to create a wide array of varieties and biotypes for diverse uses, including fibre, food, biofuel, medicine and drugs. This paper briefly reviews the available literature on the taxonomy, evolutionary origin and domestication of this plant, as well as its worldwide dispersal, in both its wild and cultivated forms. Emphasis is placed on Europe and especially on the Iberian Peninsula. Today, it is accepted that Cannabis is a monospecific genus with two subspecies, C. sativa subsp. sativa and C. sativa subsp. indica, originating in Europe and Asia, respectively, by allopatric differentiation after geographic isolation fostered by Pleistocene glacial-interglacial cycles. Palynological and phylogeographic evidence situates the Cannabis ancestor on the NE Tibetan Plateau during the mid-Oligocene. The timing and place of domestication is still a matter of debate between contrasting views that defend single or multiple Neolithic domestication centres situated in different parts of the Eurasian supercontinent, notably central/southeastern China and the Caucasus region. Recent meta-analyses have suggested that wild Cannabis may have already been spread across Europe in the Pleistocene, and its domestication could have occurred during the European Copper/Bronze ages. According to the available reviews and meta-analyses, pre-anthropic dispersal of Cannabis into the Iberian Peninsula seems to have occurred only in postglacial times, and the earlier signs of cultivation date to the Early Medieval Ages. However, the palynological and archaeological evidence used to date is insufficient for a sound assessment, and the development of thorough Iberian databases to address further meta-analysis is essential for more robust conclusions. Some clues are provided for these achievements to be fulfilled.

3CL^pro is the main protease of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology, we found 23 approved clinical drugs such as Carfilzomib, Saquinavir, Thymopentin and etc., which showed high affinity with the 3CL^pro active sites. These findings suggest that 3CL^pro inhibitors might be potential candidates for further activity detection and molecular modification.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

The Estimation of systemic risk in India is still in its infancy stage. There are several methods which are available but none of the methods are fully compatible to forecast the systemic risk since under different circumstances the factors responsible for the risk differs. In this paper the systemic risk estimation in India being carried out based on spread in daily stock market price(Difference between the bid and ask price of a share) of the top 100 firms in India according to market capitalization for the period of July2007 to March 2016. The results were compared with the Financial Stability Report published by Reserve Bank Of India for the period of March 2010 to June 2016.The results clearly indicates that there exits relationship between market illiquidity represented by spread and risks associated with the Financial System. In most of the cases the Z score (deviation from the mean/Standard Deviation) of the spread has become negative which provides the spread which is farther from the mean, also a good indicator of volatility in market and risk to financial system. It is also seen that the Systemic Risk Survey conducted by Reserve Bank of India which started during October 2011 has supported the results.

Co-integration and Causality was built to conduct studies on causality relation between carbon intensity and coal consumption leading to providing important basis for the transition to a low carbon economy. The EG two-step method was performed to study the relation between carbon intensity and coal consumption of China during 1990-2015 and the co-integration and Granger test was constructed to build up the co-integration and error correction models for analysis of the interaction between carbon intensity and coal consumption. The results showed that in long term there is a stable co-integration relation and a positive correlation between carbon intensity and coal consumption; whereas fluctuations exist in short term and there is a one-way Granger causality of carbon intensity with respect to coal consumption.

Porous MnO/C microspheres have been successfully fabricated by a fast co-precipitation method in a T-shaped microchannel reactor. The structures, compositions and electrochemical performances of the obtained MnO/C microspheres are characterized by X-ray diffraction, emission scanning electron microscopy, transmission electron microscopy (HRTEM), Brunauer–Emmett–Teller analysis, charge-discharge testing, cyclic voltammograms, and electrochemical impedance spectra. Experimental results reveal that the as-prepared MnO/C, with a specific surface area of 96.66 m²·g^–1 and average pore size of 24.37 nm, exhibits excellent electrochemical performance, with a discharge capacity of 655.4 mAh·g^–1 after cycling 50 times at 1 C and capacities of 808.3, 743.7, 642.6, 450.1, and 803.1 mAh·g^–1 at 0.2, 0.5, 1, 2, and 0.2 C, respectively. Moreover, the controlled method of using a micro-channel reactor, which can produce larger specific surface area porous MnO/C with improved cycling performance by shortening lithium-ion diffusion distances, can be easily applied in real production on a large-scale.

In this work, we report synthesis of Cu, Pt and Pd doped SnO₂ powders and their comparative CO gas sensing studies. Dopants were incorporated into SnO₂ nanostructures using chemical and impregnation methods by using urea and ammonia as precipitation agents. The synthesized samples were characterized using X-ray diffraction (XRD), Raman spectroscopy, Scanning electron microscopy (SEM) and High resolution transmission electron microscopy (HR-TEM). The presence of dopants within the SnO₂ nanostructures was evidenced from HR-TEM. Doped powders utilizing chemical methods with urea as precipitation agent presented higher sensitivities compared to the remaining, which is due to the formation of uniform and homogeneous particles resulted from the temperature assisted synthesis. The particle sizes of doped SnO₂ nanostructures were in the range of 40-100 nm. An enhanced sensitivity around 1783 was achieved with Cu doped SnO₂ when compared with two other dopants i.e., Pt (1200) and Pd: SnO₂(502). The high sensitivity of Cu: SnO₂ is due to formation of CuO and its excellent association and dissociation in the presence of CO with adsorbed atmospheric oxygen at sensor operation temperatures resulted in high conductance. Cu: SnO₂ may be an alternative and cost effective sensor for industrial applications.

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

On the eve of the Brexit process, in the context of a rising Euroscepticism that fuels the modest confidence of European citizens in their national and European institutions, the article assesses the efficiency and effectiveness of the European Parliament within the framework of the ordinary legislative procedure (co-decision). After defining and formulating the main indicators, the paper analyses the micro- and macro-performance of the European Parliament within the decision-making process from a quantitative-qualitative and a qualitative-quantitative perspective, highlighting the relativizing factors and the responsiveness of the European decision-making process to the Europeans’ needs.

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are over-expressed in different kinds of cancer, including breast, prostate and bladder carcinoma, with positive effects on cancer proliferation and chemo-resistance. For these reasons, these enzymes are potential therapeutic cancer targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing JARID1B. In particular we tested H3K4 demethylation (western blot); target gene transcription (RNAseq and real time PCR); radio-sensitivity (citoxicity and clonogenic assays) and damage accumulation (kinetics of H2AX phosphorylation). Results: we show that two compounds with completely different chemical structure can selectively inhibit KDM5 enzymes and that both compounds are capable of increasing sensitivity of breast cancer cells to ionizing radiation and H2AX phosphorylation. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in DNA damage signaling and repair and suggest new strategies for the therapeutic use of their inhibitors.

The purpose of the present study was to investigate the effects of psychological pressure on corticospinal excitability, the spinal reflex, lower limb muscular activity, and reaction times during a task involving dominant leg movements. Ten healthy participants performed a simple reaction time task by raising the heel of their dominant foot from a switch. After 20 practice trials, participants performed 20 non-pressure and 20 pressure trials in a counterbalanced order. Stress responses were successfully induced, as indexed by significant increases in state anxiety, mental effort, and heart rates under pressure. Significant increases in motor evoked potential (MEP) amplitude of the tibialis anterior muscle (TA) occurred under pressure. In terms of task-related EMG amplitude, the co-contraction rate between the soleus (SOL) and TA muscles significantly increased along with SOL and TA EMG amplitudes under pressure. Hoffmann reflexes for SOL and reaction times did not change under pressure. These results indicate that corticospinal excitability and leg muscle-related EMG activity increase homogeneously during lower limb movements that are performed under psychological pressure.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, an-tagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including inter-section points to the new generation of antidiabetic drugs. We provide insight into the effective-ness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Mangrove forests store and sequester large area-specific quantities of blue carbon (C_org). Except for tundra and peatlands, mangroves store more C_org per unit area than any other ecosystem. Mean mangrove C_org stock is 738.9 Mg C_org ha⁻¹ and mean global stock is 6.17 Pg C_org, which equates to only 0.4–7% of terrestrial ecosystem C_org stocks but 17% of total tropical marine C_org stocks. Seagrasses sequester more C_org per unit area than mangroves (179.6 g C_org m⁻²·a⁻¹) but twice the C_org sequestered by mangroves globally (15 Tg C_org a⁻¹). Mangroves sequester only 4% (range 1.3–8%) of C_org sequestered by terrestrial ecosystems, indicating that mangroves are a minor contributor to global C storage and sequestration. CO₂ emissions from mangrove losses equate to 0.036 Pg CO₂-equivalents a⁻¹ based on rates of C sequestration but 0.088 Pg CO₂-equivalents a⁻¹ based on complete destruction for conversion to aquaculture and agriculture. Mangrove CO₂ emissions account for only 0.2% of total global CO₂ emissions but 18% of CO₂ emissions from the tropical coastal ocean. Despite significant data limitations, the role of mangrove ecosystems in climate change mitigation is globally insignificant but may be more significant and effective at the national and regional scale.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

Data from Earth Observation (EO) satellites are increasingly used to monitor the environment, understand variability and change, inform evaluations of climate model forecasts and manage natural resources. Policy makers are progressively relying on the information derived from these datasets to make decisions on mitigating and adapting to climate change. These decisions should be evidence based, which requires confidence in derived products as well as the reference measurements used to calibrate, validate or inform product development. In support of the European Union’s Earth Observation Programmes Copernicus Climate Change Service, the Quality Assurance for Essential Climate Variables (QA4ECV) project fulfilled a gap in the delivery of climate quality satellite derived datasets by prototyping a robust, generic system for the implementation and evaluation of Quality Assurance (QA) measures for satellite-derived ECV climate data record products. The project demonstrated the QA system on six new long-term, climate quality ECV data records for surface Albedo, Leaf Area Index, FAPAR, NO₂, HCHO and CO. Provision of standardized QA information provides data users with evidence-based confidence in the products and enables judgement on the fitness-for-purpose of various ECV data products their specific applications.

Activation of the N-methyl D-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly that which relates pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer –term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.

In the pre era of synthetic antibodies, pharmaceutical companies depend on finding novel drugs from medicinal plants and other traditional resources; while in present, technological advances in biology, computer and robotics give the researchers the ability to rewrite and edit DNA in order to synthesize very large sets of drug candidates; these novel and improved candidates serves the basis for creating another library of drug candidates and so on until we find the right biomolecule for the disease of interest. all these technologies combined together to synthesize therapeutic antibodies for many types of cancer, autoimmune diseases, and infectious diseases, that can address diseases much more readily to very rapidly get therapeutics into patients so that we can potentially have an impact on disease. The antibodies mechanism is recognize and bind to disease cells and pinpoint the immune system to attack those cells effectively. Now a days, they dependent on computational approach to guide and accelerate the process of antibodies engineering by combination of selection system and use of high-throughput data acquisition and analysis to build and construct populations of next generation antibodies that are thermo-stable, non-immunogenic as possible, and to be administered to many humans as possible. In this review, I will discuss the latest in silico methods for antibodies engineering.

At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.

The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.

We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in expression patterns of intermediate filaments are often associated with cancer progression, in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

Within the past several decades, the emergence of new viral diseases with more severe health complications and mortality, primarily in older adults with comorbidities, is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitant reduced immunity. The emergence of new infectious coronaviruses such as SARS-CoV-2 has resulted in the coronavirus disease 2019 (COVID-19). The result is increased morbidity and mortality in persons with underlying chronic diseases and among those with compromised defense mechanisms, regardless of age and among older adults who are more likely to fit these categories. COVID-19 appears to be primarily an upper respiratory disease. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome (ARDS), lung fibrosis, cardiac t complication, acute kidney injury, hospitalization, and high mortality have been reported in older adults with COVID-19, that result from pathogen-host interactions. Here, we review potential interactions of the coronavirus and host cellular responses in relation to hallmarks of aging including genomic instability, telomere attrition, impaired autophagy, mitochondrial dysfunction, innate immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, and epigenetic alterations, that likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults.

Cu,N-TiO₂ nanotube (Cu,N-TNT) is prepared through a novel magnetron sputtering and anodic oxidation method. Then the morphology, structure and physicochemical property of Cu,N-TNT was analyzed by XRD, SEM, TEM, EDX and UV-vis-DR. The results indicate that the evenly doped copper is beneficial to the transformation of the TNT from anatase to rutile and play a key role in the morphology of the Cu,N-TNT. The doped Cu and N in the TNT influence the growth orientation of the TiO₂ crystals, which result in the lattice distortion and wider the interplanar spacing 60s-Cu,N-TNT has less band gap and stronger absorption intensity in visible region than other Cu,N-TNT samples, which make the combination rate of photogenerated electron and photogenerated hole decrease greatly, thus beneficial to its physicochemical property.

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

This paper investigates the effects of Inter-generational co-residence on health care market, and labor market outcomes, to see whether or not living under the same roof with at least one parent matters in health care market, and labor market behaviors in post-Affordable-Care Act (ACA) USA. The adopted analytical strategy involves not only looking at the gender differences in co-residence, and its effects on outcomes in the two markets, but also accounting for co-residence endogeneity following the recent literature. Unlike the recent literature that relies on instrumental variables methods, this study adopts a switching regression approach, defining inter-generational co-residence as an endogenous selection process using a binary probit equation, and modeled jointly with the extensive margins and intensive margins in the two markets. This novel approach results in a recursive trivariate probit model for each market, and estimated using penalized maximum likelihood methods. The results suggest that ACA by reorganizing the US health care market, seems to have reduced significantly disparities in health care access among males and females based on race, region of residence, place of birth, and citizenship. However not only do we observe significant differences in inter-generational co-residence status between males and females, we also find significant inequalities in the effects of co-residence on health care market, and labor market outcomes. In fact, co-residence is found to increase health care expenditure by 56.7% among females, while this figure increases to 74.2% among males. In addition co-residing individuals, while spending 69.7% more on health care annually are 1.22 times more likely to access health care, but 31% less likely to use health care intensively during the year. In the labor market, co-residence is found to reduce significantly hours of weekly labor supplied by 41% for females, and 55.6% for males. Furthermore co-residing individuals, while not significantly different in their likelihood of labor force participation, are 1.52 times less likely to work full time once they decide to participate, and also spend about 55.4% less time working in the labor market in post-ACA USA.

In this work, we focus on investigating electrothermal flow in a rotating electric field (ROT-ETF), with primary attention paid to the horizontal traveling-wave electrothermal (TWET) vortex induced at the center of the electric field. The frequency-dependent flow profiles in the microdevice are analyzed using different heat transfer models. Accordingly, we address in particular the importance of electrode cooling in ROT-ETF as metal electrodes of high thermal conductivity while substrate material of low heat dissipation capability are employed to develop such microfluidic chips. Under this circumstance, cooling of electrode array due to external natural convection on millimeter-scale electrode pads for external wire connection occurs and makes the internal temperature maxima shift from the electrode plane to a bit of distance right above the cross-shaped interelectrode gaps, giving rise to reversal of flow rotation from a typical repulsion-type to attraction-type induction vortex, which is in good accordance with our experimental observations of co-field TWET streaming at frequencies on the order of reciprocal charge relaxation time of the bulk fluid. These results point out a way to make a correct interpretation of out-of-phase electrothermal streaming behavior, which holds great potential for handing high-conductivity analytes in modern microfluidic systems.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining nolecules, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Direct georeferencing of airborne pushbroom scanner data usually suffers from the limited precision of navigation sensors onboard of the aircraft. The bundle adjustment of images and orientation parameters, used to perform geocorrection of frame images during the post-processing phase, cannot be used for pushbroom cameras without difficulties: it relies on matching corresponding points between scan lines, which is not feasible in the absence of sufficient overlap and texture information. We address this georeferencing problem by equipping our aircraft with both a frame camera and a pushbroom scanner: the frame images and the navigation parameters measured by a couple GPS/Inertial Measurement Unit (IMU) are input to a bundle adjustment algorithm; the output orientation parameters are used to project the scan lines on a Digital Elevation Model (DEM) and on an orthophoto generated during the bundle adjustement step; using the image feature matching algorithm Speeded Up Robust Features (SURF), corresponding points between the image formed by the projected scan lines and the orthophoto are matched, and through a least-squares method, the boresight between the two cameras is estimated and included in the calculation of the projection; finally, using Particle Image Velocimetry (PIV) on the gradient image, the projection is deformed into a final image that fits the geometry of the orthophoto. We apply this algorithm to five test acquisitions over Lake Geneva region (Switzerland) and Lake Baikal region (Russia). The results are quantified in terms of Root Mean Square Error (RMSE) between matching points of the RGB orthophoto and the pushbroom projection. From a first projection where the Interior Orientation Parameters (IOP) are known with limited precision and the RMSE goes up to 41 pixels, our geocorrection estimates IOP, boresight and Exterior Orientation Parameters (EOP) and produces a new projection which RMSE with the reference orthophoto is around two pixels.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

The dye effluent is usually difficult to be degraded by conventional wastewater treatment in leather industry. In order to develop efficient and cost-effective treatment methods, we evaluate the effect of white-rot fungus immobilization for dye decolorisation in this paper. The Phanerochaete chrysosporium BKM-F-1767 was used for immobilization. This research found that the white-rot fungus immobilization had an obviously decolorisation effect in dye wastewater treatment, and plant carriers such as sorghum stalk and corn cob were helpful to the growth of Phanerochaete chrysosporium in white-rot fungus immobilization. Due to the stability and recyclability, the white-rot fungus co-immobilization was considered as the most suitable treatment for decolorisation of dye effluent which enjoyed the advantages of both adsorption immobilization and entrapment immobilization. Furthermore, the dye decolorisation evaluation was carried out to find the most suitable carrier for co-immobilization, and it found that sorghum stalk - calcium-alginate gel spherical particle (SS-CGPB) has better decolorisation effect than corn cobs - calcium-alginate gel spherical particle (CC-CGPB), and the dye decolorisation rate was 86.77%. After 5 cycles, the dye decolorisation rate was 85.87% which indicated the SS-CGPB preserved functional integrity successfully. By further analyzing the biodegradation process with white-rot fungus immobilization, the intermediate products were observed and the degradation pathway of acid golden yellow dye molecular was proposed. The results showed that the C-N single bonds attached to the central benzene in the dye molecule were attacked and destroyed in white-rot fungus co-immobilization treatment, thus the structure of dye molecule could be successfully degraded into small molecules which would be more easily treated by conventional treatment methods. Therefore, the white rot fungus co-immobilization might be appropriate for pre-treatment as an important biotechnology for the advanced treatment of dye effluent.

It is well known that that there is an intrinsic link between the financial and energy sectors, which can be analyzed through their spillover effects, which are measures of how the shocks to returns in different assets affect each other’s subsequent volatility in both spot and futures markets. Financial derivatives, which are not only highly representative of the underlying indices, but can also be traded on both the spot and futures markets, include Exchange Traded Funds (ETFs), a tradable spot index whose aim is to replicate the return of an underlying benchmark index. When ETF futures are not available to examine spillover effects, “generated regressors” are useful for constructing both Financial ETF futures and Energy ETF futures. The purpose of the paper is to investigate the co-volatility spillovers within and across the US energy and financial sectors in both spot and futures markets, by using “generated regressors” and a multivariate conditional volatility model, namely Diagonal BEKK. The daily data used are from 1998/12/23 to 2016/4/22. The data set is analyzed in its entirety, and are also subdivided into three distinct subsets. The empirical results show there is a significant relationship between the Financial ETF and Energy ETF in the spot and futures markets. Therefore, financial and energy ETFs are suitable for constructing a financial portfolio from an optimal risk management perspective, and also for dynamic hedging purposes.

Contact-based co-culture of fibroblasts and keratinocytes is important to study the structure and functions of the wound bed. Co-culture of these two cell types in direct contact with each other has been challenging, requiring high serum concentrations (up to 10%), feeder systems and a range of supplemental factors. These approaches are not only technically demanding, but also present scientific, cost and ethical limitations associated with high-serum concentrations. We have developed two reduced-serum approaches (1-2%) to support contact-based co-culture of human dermal fibroblasts (HDFa) and human epidermal keratinocytes (HaCaT). The two approaches include (1) Specialized cell culture media for each cell type mixed in a 1:1 ratio (KGM+FGM), and (2) Minimal media supplemented with cell-specific growth factors (MEM+GF). Co-culture could be successfully achieved by co-seeding (two cell types were introduced simultaneously), or in a layered fashion (keratinocytes seeded on top of confluent fibroblasts). With wound scratch assays, the co-cultured platforms could demonstrate cell proliferation, migration and wound closure. The reduced-serum conditions developed are simple, easy to formulate and adopt, and based on commonly-available media components. These contact-based co-culture approaches can be leveraged for wound and skin studies, and tissue bioengineering applications, potentially reducing concerns with high-serum formulations.

A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-Bampa) was validated using Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-Bampa were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for the 14 BCS class I-IV drugs cited in the FDA guidance (including other drugs as acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-Bampa. Apparent permeability (Papp) was compared to literature fraction dose absorbed in humans (Fa%). Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-Bampa performance. Mannitol and metoprolol Papp values across Franz-Bampa were lower (3.20 x 10-7 and 1.61 x 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 x 10-5 and 2.55 x 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed similar log linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-Bampa method for use during drug discovery process.

This study reports on empirical findings of participatory design workshops for the development of a supportive user experience design system in the automotive. Identifying and addressing this area with traditional research methods is problematic due to the different UX design perspectives that might be conflicting and the related automotive domain limitations. To help resolve this problem, we conducted research with 12 User Experience (UX) designers through individual participatory prototyping activities to gain insights on their explicit, observable, tacit and latent needs. These activities allowed us to explore their motivation to use different technologies; the system's architecture; detailed features of interactivity and describe user needs including Efficiency, Effectiveness, Engagement, Naturalness, Ease of Use, Information retrieval, Self-Image awareness, Politeness, and Flexibility. Our analysis led us to design implications that translate participants' needs into UX design goals, informing practitioners on how to develop relevant systems further.

Crotoxin (CTX), the predominant toxin in Crotalus durissus terrificus snake venom (CdtV), has anti-inflammatory and immunomodulatory effects. Despite its inhibitory action on neutrophil migration and phagocytosis, CTX does not directly affect the production of reactive oxygen species (ROS) by the neutrophils. In contrast, it enhances the generation of reactive oxygen and nitrogen intermediates by macrophages. Given the importance of macrophage-neutrophil interactions in innate antimicrobial defense, the aim of this study was to investigate the effect of CTX on neutrophil ROS production and killing activity, either through CTX-treated macrophage co-culture or conditioned medium of CTX-treated macrophages. The results showed an important modulatory action of CTX on the neutrophil function as well as neutrophil-macrophage interactions, as demonstrated by the increased production of hydrogen peroxide, hypochlorous acid, nitric oxide and TNF-α, along with the increased fungicidal activity of neutrophils.

This study investigated whether biogas reactor performance, including microbial community development, in response to a change in substrate composition is influenced by initial inoculum source. Test reactors were first started with two different inocula and operated with the same grass-manure mixture for more than 120 days. These reactors initially showed great differences depending on inoculum source, but eventually showed similar performance and overall microbial community structure. At the start of the present experiment, the substrate was complemented with milled feed wheat, added all at once or divided into two portions. The starting hypothesis was that process performance depends on initial inoculum source and microbial diversity, and thus that reactor performance is influenced by the feeding regime. In response to the substrate change, all reactors showed increases and decreases in volumetric and specific methane production, respectively. However, specific methane yield and development of the microbial community showed differences related to initial inoculum source, confirming the hypothesis. The different feeding strategies had however only minor effects on process performance and overall community structure, but still induced differences in the cellulose-degrading community and in cellulose degradation.

Elevated antimony concentrations in aqueous environments from anthropogenic sources is becoming of global concern, here iron oxides are known to strongly adsorb aqueous antimony species with different oxidation states, but the effect of silica on the removal characteristics is not well understood despite being a common component in the environment. In this study, ferrihydrite was synthesized at various Si/Fe molar ratios to investigate its adsorption and co-precipitation behaviors with aqueous antimony anionic species, Sb(III) and Sb(V). The XRD analyses of the precipitates showed two broad diffraction features at approximately 35° and 62° 2θ, which are characteristic of 2-line ferrihydrite, no significant shifts in peak positions in the ferrihydrite regardless of the Si/Fe ratios. The infrared spectra showed a sharp band at ~990 cm⁻¹, corresponding to asymmetric stretching vibrations of Si-O-Fe bonds which increased in intensity with increasing Si/Fe molar ratios. Further, the surface charge on the precipitates became more negative with increasing Si/Fe molar ratios. The adsorption experiments indicated that Sb(V) was preferentially adsorbed at acidic conditions and decreased dramatically with increasing pH while the adsorption rate of Sb(III) ions was independent of pH, however, the presence of silica suppressed the adsorption of both Sb(III) and Sb(V) ions. The results showed that Sb(III) and Sb(V) ions were significantly inhibited by co-precipitation with ferrihydrite even in the presence of silica by isomorphous substitution in the ferrihydrite crystal structure.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We here evaluated available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining antidiabetics, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To our best, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other novel antidiabetics and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.

In the recent decade, Building Information Modelling (BIM) has widely been adopted in the Architecture, Engineering and Construction (AEC) industry and completely upended the way we build. While BIM continues gain momentum in the industry, it has also attracted increasing attentions from researchers. However, most of the current study focuses on reviewing BIM for management, BIM for green building, BIM for infrastructure and BIM for Facilities Management (FM). There are few studies about Global BIM review and to discuss their complex inter-connections. In this study, we adopted a scientometric analysis method to review global BIM research from 2004-2019. A total of 1455 scholarly bibliographic records obtained from Web of Science Core Collection databased were established for the analysis. This study has identified the top productive and influential researchers, research institutes, regions/countries, subject categories and journals in the BIM field. In addition, 11 clusters of Global BIM research were also identified including construction project, green BIM, construction safety planning, automated IFC-based workflow and so on. Authors distinguished 11 clusters of global BIM research into 3 stages, namely formulating stage, accelerating stage and transforming stage. Furthermore, authors reviewed the BIM policy of Singapore and observed there is a co-production relationship between evolution of BIM policy and global BIM research. These findings provide valuable information for researchers, practitioners and policy makers by visualizing the current progress in the research field of BIM and highlighting future research needs.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Background: Patients with mild cognitive impairment end up progressing to Alzheimer’s disease (AD) leading to straining burden on public health. R. officinalis long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aims of the review were to summarize the qualitative and quantitative aspects of R.O and its active constituents in enhancing the cognition. MATERIALS AND METHOD Google scholar and PubMed structured search to find relevant studies that assessed the effect of R.O extract or any of its active constituents on cognitive performance in animals. Data extraction: Following information from each included study was extracted: (1) article information (2) characteristics of study animals (3) type of intervention; type, dose, duration, and frequency of administration of R.O (4) type of outcome measure. Data synthesis: Data were analyzed using Review Manager (RevMan 5.3, 2014] and meta-analysis was performed for the outcome measures on all relevant tasks within the included papers by computing the standardized mean difference ps. RESULTS. 23 studies for qualitative and fifteen for meta-analysis were selected. From fifteen included papers, 22 studies with 35 comparisons were meta-analyzed. Effect sizes for intact animals and impaired animals respectively was (mean g and 95% CI 1.19 [0.74, 1.64; 0.57 [0.19,0.96]. The R. officinalis had positive effect on both groups of animals. The subgroup analyses exhibited substantial unexplained heterogeneity between studies. Mechanisms of R.O was anticholinesterase, procholinergic, antioxidant, anti-amyloid, neuroprotective and anti-inflammatory agent CONCLUSIONS: R.O improves cognitive function. Limitations: Considerable heterogeneity between studies.

Simulation tools capturing the interactions of communication and electrical system operation represent a powerful support for fully assessing the potential benefits and impacts of ICT in future smart power distribution network. A strong interest is upon the possibility of exploiting the last generation communication systems for supporting the transition of distribution network towards a smart grid scenario. Having in mind the above, the authors propose a numerical co-simulation tool useful to thoroughly understand the impact of the communication networks on the performance of whole power system dynamics. The co-simulation tool has been purposely developed to simulate the highly time-critical smart grid application of fault management and network reconfiguration and permits reproducing and evaluating the behavior of the public mobile telecommunication system 4G Long Term Evolution (LTE), as communication technology for smart grid applications. Results of the paper demonstrates that LTE provides good performances for supporting the data communication required to perform fault location, extinction and a subsequent network reconfiguration in smart power distribution networks.

Ocean big data is the scientific practice of using big data technology in the marine field. Data from satellites, manned spacecraft, space stations, airship, unmanned aerial vehicles, shore-based radar and observation stations, exploration platforms, buoys, underwater gliders, submersibles, and submarine observation networks are seamlessly combined into the ocean’s big data. Increasing numbers of scholars have tried to fully analyze the ocean’s big data. To explore the key research technology knowledge graphs related to ocean big data, articles between 1990 and 2020 were collected from the “Web of Science”. By comparing bibliometric software and using the visualization software Cite-Space, the pivotal literature related to ocean big data, as well as countries, institutions, categories, and keywords, were visualized and recognized. Journal co-citation analysis networks can help determine the national distribution of core journals. Co-citation analysis networks for documents show authors who are influential at key technical levels. Key co-occurrence analysis network keywords can determine research hot spots and research frontiers. The three supporting elements of marine big data research are shown in the co-citation network. These elements are author, institution, and country. By examining the co-occurrence of keywords, the key technology research directions for future marine big data were determined.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

The consumption of alcohol and drugs of abuse among pregnant women has experienced a significant increase in the last decades. Optimal maternal nutritional status is of great importance for proper fetal development, yet is often altered with alcohol or drugs consumption. There is a lack of information on the effects of alcohol and drugs on maternal nutritional status, so the focus of this review was to provide an overview on nutrional status of mother and fetus in abusers pregnant women. Alcohol and drugs consumption can adversely affect the quality and quantity of proper nutrient supply and energy intake, resulting in malnutrition especially of micronutrients (vitamins, omega-3, folic acid, zinc, choline, iron, copper, selenium). When maternal nutritional status is compromised by alcohol and drugs essential nutrients are not available for the fetus, this can result in suboptimal outcomes like Intrauterine Growth Restriction (IUGR) or Fetal Alcohol Spectrum Disorder (FASD). It is critical to determine a means to resolve and reduce the physical and neurological malformations that develop in the fetus as a result of prenatal alcohol and drugs exposure combined with poor maternal nutrition. Prenatal nutrition interventions are required that may prevent or alleviate the development of such abnormalities.

The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Degussa P25 is a benchmark form of TiO₂ used worldwide in photocatalysis studies. Currently no such benchmark exists for co-catalysts, which are essential for many photocatalytic reactions. Here, we present the preparation of Pt nanocluster co-catalysts on TiO₂ using an unmodified commercial source and equipment that is commonly available. Transmission electron microscopy reveals that the procedure produces TiO₂ decorated with Pt atom and nanoclusters (1-5 atoms). Optical reflectance and X-ray diffraction measurements show that the procedure does not affect the TiO₂ polymorph or UV-Vis absorbance. Gas phase photocatalytic splitting of heavy water (D₂O) shows that the Pt nanocluster decorated TiO₂ outperforms Pt nanoparticle (produced by photodeposition) decorated TiO₂ in D₂ production. Pt nanoclusters, produced directly from a commercial source, with high co-catalyst activity are prime candidates to be used in benchmark photocatalytic reactions.

Hormones must be balanced and dynamically controlled for the Female Reproductive Tract (FRT) to function correctly during the menstrual cycle, pregnancy, and delivery. Gamete selection and successful transfer to the uterus, where it implants and pregnancy occurs, is supported by the mucosal epithelial lining of the FRT ovaries, uterus, cervix, fallopian tubes, and vagina. Successful implantation and placentation in humans and other animals rely on complex interactions between the embryo and a receptive female reproductive system. The FRT's recent breakthroughs in three-dimensional (3D) organoid systems now provide critical experimental models that match the organ's physiological, functional, and anatomical characteristics in vitro. This article summarizes the current state of the art on organoids generated from various parts of the FRT. The current analysis examines recent developments in the creation of organoid models of reproductive organs, as well as their future directions.

This paper addresses pastoral resilience by drawing out the coping strategies and mechanisms utilized by the Maasai Pastoralists through a food system approach, based on the study findings of an anthropological study of pastoralism in Laikipia County, Rift Valley, Kenya. This paper is guided by the specific objectives aimed at establishing actors and their roles, and describing the institutional settings and changes in pastoralism. Using a new institutionalism approach, the paper focuses not only on the actors and their roles in pastoralism but also on how internal and external forces regulate access and use of common pool resources (CPRs) resulting in sustainability of the food system. We argue that this has an impact on the practice of pastoralism that continually defines and redefine the actors’ roles as well as elicit the value of pastoral economies and benefits accrued to a wide range of actors hence reinforcing pastoral resilience. The study also identified institutional settings and changes that lead to pastoral survival resulting from the country’s devolved system of governance. Data collection was through in-depth interviews, key informant interviews, focus group discussions and unstructured observations in the pastoral regions. The findings reveal that actors at the household, state, non-state, and service providers have developed varied coping strategies and mechanisms that sustain pastoralism. The study also identified institutional settings and changes that promote pastoral resilience; notably, private land ownership patterns, co-management of livestock markets, commercialization of herding, decentralization of livestock services, holistic management of pasturelands and the use of water-shed management plans. As a result, increased scholarship and advocacy in regards to the concept of co-management of livestock markets, is recommended as a means of understanding pastoral resilience that the food system exhibits.

Hydrogen is useful as a fuel and could be produced by a variety of means. One approach uses artificial photosynthesis where energy from sunlight powers the splitting of water into hydrogen and oxygen. But, biological methods for producing hydrogen has emerged strongly over the past decades. In particular, specific microorganisms could use different substrates to produce hydrogen at differing yields. Such fundamental discoveries with industrial applications thus motivated the use of metabolic engineering approaches and methodologies in enhancing biological hydrogen production through a series of enzyme over-expression, pathway debottlenecking, and gene deletion. However, such approaches heavily rely on the selection of an appropriate microbial chassis for biohydrogen production. With the proper strain in hand, use of alternative substrates may engender greater hydrogen productivities. But learning from the bioprocessing field, co-culture of two compatible microorganisms have been sought after for improving biohydrogen production. In addition, thermophilic microbes may also be useful candidates for exploiting hydrogen production from composting. Future outlook in the field looks into filling our gaps in understanding of the metabolic network that feeds into hydrogen production in different organisms. But, more importantly, problems such as reduced growth rate in engineered microbes point to fundamental issues with using genetically engineered microorganisms for improved biohydrogen production, to which clever bioprocess engineering may yield solutions.

A high proportion of dogs and cats are fearful during veterinary visits, which in some cases may escalate into aggression. Here, we discuss factors that contribute to negative emotions in a veterinary setting and how these can be addressed. The set-up of the waiting area (e.g. spatial dividers; elevated places for cat carriers), tailoring the examination and the treatment to the individual, considerate handling (minimal restraint when possible, avoiding leaning over or cornering animals) and offering high-value food or toys throughout the visit can promote security and, ideally, positive associations. Desensitisation and counterconditioning are highly recommended both to prevent and address existing negative emotions. Some negative experiences such as short-term pain from injections can be minimised by using tactile and cognitive distractions. Preemptive analgesia is recommended for known painful procedures. Recommendations for handling fearful animals to minimise aggressive responses are discussed. However, anxiolytics or sedation should be used whenever there is a risk of traumatising an animal or for safety reasons. Stress-reducing measures can decrease stress and fear in patients and consequently their owners – thus strengthening the relationship with the clients as well as increasing the professional satisfaction of veterinary staff.

Urban areas face daunting economic challenges that have increased in scope in recent years. At the same time, cities provide for opportunities for growth and value creation. The interplay of these challenges and opportunities represents the area of intervention for policymakers and researchers. However, the traditional approach to urban policy, deriving from the managerial and economic policy theories, shows difficulties mainly related to the capacity to counterbalance the interests and expectations of a multitude of stakeholders participating to the value co-creation process and to bring all different components to synergically contribute to the sustainability of the system. The Author proposes an innovative approach to urban public policy, by adopting the theoretical corpus of the Viable Systems Approach ("VSA"). Urban planning will be particularly analysed, as systemic components of urban areas, with the aim to investigate the decision-making processes for an integrated, efficient, effective and sustainable management of the territory as a multidimensional, multisectoral and multi-stakeholder entity. By recovering different settings, the VSA intends the co-creation of value as the capacity of the viable systems to increase its surviving chances in its own context. The value derives, first of all, from the strategic decisions aimed at finding both dyadic and context consonance. Through its strategic decisions, the Governing Body of the territory develops a specific system as the overall synthesis of all possible systems organised within a specific area, identifying pattern of development agreed by the several stakeholders of the territory. In the dynamics of value co-creation in systemic multi-subjective organizations, where the level of complexity is particularly significant, the research for consonance among different stakeholders is particular important in order to achieve the most value for the territory. In this respect, the VSA may constitute a valid tool, helping to find the necessary capacities to imagine evolutionary paths towards new competencies.

With the progress of immunotherapy in cancer, oncolytic viruses (OVs) are getting more and more attention during the past decade. Due to their cancer-selective and immunogenic property, OVs are considered ideal candidates to be combined with immunotherapy to increase both specificity and efficacy in cancer treatment. OVs preferentially replicate in and lyse cancer cells, generating pathogen-associated molecular patterns (PAMPs) and danger (damage)-associated molecular patterns (DAMPs). These signals trigger innate immune response to modulate the solid tumor microenvironment, resulting in in situ autovaccination leading to adaptive anti-virus and anti-tumor immunity. Here, we summarize the conceptual updates of oncolytic virotherapy, immunotherapy, and the strategies to enhance the virus-mediated anti-tumor immune response, including: 1. Arm OVs with cytokines to modulated innate and adaptive immunity; 2. Combine OVs with immune checkpoint inhibitors to release T cell inhibition; 3. Combine OVs with immune co-stimulators to enhance T cell activation.

Biocompatible and biodegradable poly(butylene succinate-co-adipate) (PBSA)/hexadecylamine-modified PPZn (m-PPZn) nanocomposites were prepared using a melt mixing process. Experimental results of wide-angle X-ray diffraction and transmission electron microscopy revealed that the stacking layers of the m-PPZn were partially intercalated and partially exfoliated into the PBSA polymer matrix. The isothermal crystallization kinetics of PBSA/m-PPZn nanocomposites were studied at the temperature range of 62−70 °C and the half-time for crystallization of 3 wt % PBSA/m-PPZn nanocomposite was reduced by 27−35% compared with that of pure PBSA. This finding suggests that the incorporation of m-PPZn might cause the heterogeneous nucleation and the subsequent crystallization growth, which enhances the isothermal crystallization rate of PBSA/m-PPZn nanocomposite. The biodegradation rates of PBSA using Lipase from Pseudomonas sp. increase as the contents of m-PPZn increase. The degradation behavior of the neat PBSA investigated using the change of weight-average molecular weight belongs to exo-type hydrolysis activity. It is necessary to point out that the change of degree of crystallinity and degradation rate are almost linearly proportional to the loading of hexadecylamine-modified PPZn. This finding would provide an important information for the manufacturing biodegradable PBSA nanocomposites.

In the next decade, further digitalisation of the entire wind energy project lifecycle is expected to be a major driver for reducing project costs and risks. In this paper, a literature review on the challenges related to implementation of digitalisation in the wind energy industry is first carried out, showing that there is a strong need for new solutions that enable co-innovation within and between organisations. Therefore, a new collaboration method called the WeDoWind Ecosystem is developed and demonstrated. The method is centred around specific "challenges", which are defined by "challenge providers" within a topical "space" and made available to participants via a digital platform. The data required in order to solve a particular "challenge" is provided by the "challenge providers" under the confidentiality conditions they specify. The method is demonstrated via a case study, the EDP Wind Turbine Fault Detection Challenge. Six submitted solutions using diverse approaches are evaluated. Two of the methods perform significantly better than EDP’s existing method in terms of Total Prediction Costs (saving up to €120,000). The WeDoWind Ecosystem is found to be a promising solution for enabling co-innovation in wind energy, providing a number of tangible benefits for both challenge and solution providers.

Proper species identification from ancient DNA samples is a difficult task that sheds light on the evolutionary history of pathogenic microorganisms. The field of palaeomicrobiology has undoubtedly benefited from the advent of untargeted metagenomic approaches that use next-generation sequencing methodologies. Nevertheless, assigning ancient DNA at the species level is a challenging process. Recently, the gut microbiome analysis of three pre-Columbian Andean mummies [1](Santiago-Rodriguez et al. 2016) has called into question the identification of Leishmania in South America. Here, the metagenomic data filed in MG-RAST (Metagenomics RAST server) were used for a further attempt to identify members of the Trypanosomatidae family infecting these ancient remains. For this purpose, we used two metagenomic analysis tools. In the first step, data were analysed using the ultrafast metagenomic sequence classifier, based on exact alignment of k-mers (Kraken). In the second step, we used Bowtie2, an ultrafast and memory-efficient tool for aligning sequencing reads to long reference sequences. We then compared the output results. These approaches highlight some interesting findings on potential infections by human pathogenic trypanosomatids in these three pre-Columbian mummies.

Abstract: This work is part of the interest of solving the problems of water contamination with last generation pollutants, for which a novel and in an aqueous medium FeBTC material incorporated with magnetite nanoparticles was proposed. That material was synthesized by in situ solvothermal method, the Fe3O4 nanoparticles were added during the Fe-BTC MOF synthesis and used in the drug’s adsorption. The materials were characterized by XRD, FTIR and Raman spectroscopy, and N2-physisorption at 77 K. Fe3O4-FeBTC material showed a maximum adsorption capacity of 357.1 mg g−1 for diclofenac sodium, 70.9 mg g−1 for naproxen sodium, and 122.9 mg g−1 for Ibuprofen. A pseudo-second-order kinetic model can describe the adsorption process, and the thermodynamic study revealed that the adsorption of the three drugs was a feasible, spontaneous, and exothermic process. The incorporation of magnetite nanoparticles in the FeBTC considerably increased the adsorption capacity of pristine FeBTC. Also, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing its thermal and aqueous media stability. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played a vital role in drug adsorption. The competition of sites in the multicomponent mixture's adsorption showed selective adsorption at diclofenac sodium and naproxen sodium.

Polymer-based piezoelectric biomaterials have already proven their relevance for tissue engineering applications. Further, the morphology of the scaffolds plays also an important role in cell proliferation and differentiation. The present work reports on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), a biocompatible, biodegradable and piezoelectric biopolymer that has been processed in different morphologies, including films, fibres, microspheres and 3D scaffolds. Further, the corresponding magnetically active PHBV-based composites were also produced. The effect of the morphology on physico-chemical, thermal, magnetic and mechanical properties of pristine and composites samples was evaluated, as well as their cytotoxicity. It was observed that the morphology does not strongly affect the properties of the pristine samples but the introduction of cobalt ferrites induces changes in the degree of crystallinity that could affect the applicability of prepared biomaterials. Young modulus is dependent of the morphology and also increases with the addition of cobalt ferrites. Both, pristine and PHBV/cobalt ferrite composite samples are no cytotoxic, indicating their suitability for tissue engineering applications.

There are two contrary opinions regarding the risk if mainland China (MC) moves away from its zero-COVID policy. Some experts think the risk shall be much lower than influenza as per MC’s own COVID-19 case fatality rate (CFR), while some other experts think the risk shall be much higher than influenza as per the COVID-19 CFRs of other regions. We elucidate here that this and multiple other striking differences in the CFR between various scenarios all support and substantially resulted from the view that good IDM is highly powerful to mitigate COVID-19, where IDM (isolation-disinfection-maintenance) means isolation of COVID-19 cases from other people, disinfection of their living environments, and health maintenance (e.g., rest, nutrition, breathing). The high effect of good IDM is also supported by the theoretic functions of IDM in minimizing co-infections and maintaining body functions, and the fact that all the 505 COVID-19 deaths reported in MC in 2022 before May 5 died directly of severe underlying diseases with COVID-19. Although it is tough for people in poverty to obtain good IDM, good IDM can be feasible at home for the most mild cases and in hospitals for the most severe cases. Therefore, good IDM can be crucial to mitigating COVID-19 worldwide. It also suggests that the risk for China to end its zero-COVID policy depends on China’s control policies or measures. Based on the effect of IDM, the cautious co-existence policy was proposed for COVID-19 control. This policy could reduce the whole death toll in MC because good IDM is non-specific and can reduce deaths of various other diseases. The cautious co-existence policy (non-specific) and the vaccination policy (specific) aid each other to mitigate COVID-19, and they cannot replace each other. Those who are qualified in health for vaccination should be vaccinated against COVID-19 timely.

Logistics Engineering has transcended over the decades into an approach for competitive benefits in organisational performance and logistics efficiency. Most industries are recognising that significant savings are available to companies that are able to ordinate and improve within their logistics operations. Companies today face great challenges because the successful supply of many products and services needs to the effective integration of logistics activities across a prolongation supply chain and an increasing geographical separation. Moreover, logistics integration approach involves both internal integration for an ordinated, unified process as well as relationships to react flexibly, changeability, and responsibility to customer's demands. In this study, by using of Fuzzy Vikor (F-Vikor), the best combination of RIR was selected and RIR Locating was done. The main aim of this paper is survey and design of the integrated operational logistics network (IOLN) and also, a proposed IOLN to integration of the Iran Khodro Co Supply Network.

This paper presents a new methodology that provides the analysis of surface texture changes in areas adjacent to the volcano and its impact product of volcanic activity. To do this, algorithms from digital image processing such as the co-occurrence matrix and the wavelet transform are used. These methods are working on images taken by the Landsat satellite platform sensor 5 TM and Landsat 7 ETM + sensor, and implemented with the purpose of evaluating superficial changes that can warn of surface movements of the volcano. The results were evaluated by similarity metrics for grayscale images, and validated in two different scenarios that have the same type of eruption, but differ, essentially, in climate and vegetation. Finally, the proposed algorithm is presented, setting the parameters and constraints for implementation and use.

Contemporary literature dealing with the governance and exploitation of common-pool natural resources was initiated by Elinor Ostrom in 1990, and has been growing fast ever since. On the contrary, within the same research stream, the study of the presence and economic role of common resources in entrepreneurial organizations is, to date, under-researched. This work endeavors to fill some gaps in this research perspective by: (i) spelling out a new-institutionalist framework for the analysis of the accumulation and governance of common capital resources within organizational boundaries; (ii) considering co-operative enterprises as the organizational form that, on the basis of historical record, and of behavioral and institutional characteristics, demonstrated to be most compatible with a substantial role for common and non-divided asset-ownership and with its governance thereof; (iii) evidencing and explaining the strong connection between cooperative longevity and the presence of non-divided asset ownership. The economic forces influencing the optimal level of self-financed common capital resources in co-operatives are enquired. Conclusions to the paper evidence the main reasons why the new approach can better explain than preceding ones the economic sustainability and longevity of cooperative enterprises.

In the last decade, the tremendous improvement in the sensitivity and also affordability of Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) have revolutionized its application in pharmaceutical analysis, resulting in wide-spread of employing LC-MS/MS for determining pharmaceutical compounds including anticancer drugs in pharmaceutical research and also industries. Currently, LC-MS/MS has been widely used to quantify small molecule oncology drugs in various biological matrices to support preclinical and clinical Pharmacokinetic studies in R & D of oncology drugs. This mini-review article will describe the state-of-the art LC-MS/MS and its application in rapid quantification of small molecule anticancer drugs. In addition, efforts have also been made in this review to address several key aspects in the development of rapid LC-MS/MS methods, including sample preparation, chromatographic separation and matrix effect evaluation.

This study uses data from the pilot project "Community Monitoring for Better Health and Education Services Delivery Project'' in Burkina Faso, to model the joint impact of generic essential drugs and nursing staff supplies constraints on access to primary health care in the country. The results show that statistical endogeneity of supply side constraints are present in the standard univariate probit specification of access to care. However, when accounted for, the resulting Trivariate Probit model shows that although shortages of generic essential drugs supply do not seem to constitute a significant barrier to access in Burkina Faso, shortages in nursing staff supply do. In fact, the likelihood of primary care access is reduced by 85.5% among those that reported having experienced a shortage in nursing staff, while paradoxically increasing by 60.3% among those that reported having experienced a shortage in generic essential drugs. A potential explanation for these findings is that overall the health care needs in the three surveyed regions in the country were more linked to primary health care services consumption from nurses, although further research would be important to clearly elucidate the position of health goods such as generic essential drugs.

The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made fighting of the COVID-19 pandemic is a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in the lung tissues. Mutations and co-mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, We highlight 128 single mutations and 35 co-mutations in the unique SARS-CoV-2 ORF10 variants in this article. The possible predicted effects of these mutations and co-mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.

Loyalty is one of the greatest intangible assets that any organization can possess and improving client loyalty is a primary marketing goal that can have a significant financial impact on any business. This quantitative study examined the mediating role of communication on the relationship between satisfaction and loyalty (attitudinal and behavioral) in veterinary clinics, along with the moderating roles of trust, commitment, perceived value, and relational characteristics. Responses collected from 351 pet-owners through social media were analyzed using descriptive and inferential statistics. The results show that attitudinal loyalty (AL) has a strong positive relationship with communication at multiple points in a veterinary clinic whereas the relationship with behavioral loyalty was not as clear. Additional findings suggest that AL, which is influenced by trust in the veterinarian, communication from staff members and commitment, has a strong positive relationship with behavioral intentions, increases the number of products and services that a pet-owner consumes at his or her primary veterinary clinic, and attenuates the role of cost in receiving veterinary care. These findings can help veterinary clinic owners and managers in developing and implementing relationship strategies that improve pet-owner loyalty. The article that follows is a synopsis of the author’s dissertation.

Knowing professionals’ attitudes is the basis for the development of skills for dealing with drug dependence. These attitudes may affect patients’ clinical safety and the cost-benefit ratio of the interventions. The goal of this study was to assess emergency and mental health nurses’ attitudes and perceptions towards alcoholics. A multicenter prospective descriptive study was conducted in six hospitals with 167 emergency and mental health nurses. Nurses classified alcoholics as sick individuals, although there was a tendency to feel comfortable working with them. Results indicated that these professionals had a rejecting attitude towards moderate alcohol consumption. We found a significant association between the attitude of the nurse and gender, with the degree of rejection towards the alcoholic being higher in men than in women and with less punitive attitudes in professionals from 0 to 11 years of professional experience.

Background: The febrile patient from tropical areas, in which emerging arboviruses are endemic, represent a diagnostic challenge and potential co-infections with other pathogens (i.e bacteria or parasites) are usually overlooked. Objectives: We present a case of an elderly woman diagnosed with dengue, chikungunya and Leptospira interrogans co-infection. Study Design: Case report. Results: An 87-year old woman from Colombia complained of upper abdominal pain, arthralgia, myalgia, hyporexia, malaise and intermittent fever accompanied with progressive jaundice. She had a medical history of chronic heart failure (Stage C, NYHA III), without documented cardiac murmurs, right bundle branch block, non-valvular atrial fibrillation, hypertension, and chronic venous disease. Her cardiac and pulmonary status quickly deteriorated after 24 hours of her admission without electrocardiographic changes and she required ventilatory and vasopressor support. In the next hours the patient evolved to pulseless electrical activity and then she died. Dengue IgM, NS1 ELISA, MAT for Leptospira interrogans and RT-PCR for chikungunya, were positive. Discussion: This case illustrates a multiple co-infection in a febrile patient from a tropical area of Latin America that evolved to death.

This paper discusses the computer-aided (CAD) classification between Hepatocellular Carcinoma (HCC), i.e., the most common type of liver cancer, and Liver Abscess, based on ultrasound image texture features and Support Vector Machine (SVM) classifier. Among 79 cases of liver diseases, with 44 cases of HCC and 35 cases of liver abscess, this research extracts 96 features of Gray-Level Co-occurrence Matrix (GLCM) and Gray-Level Run-Length Matrix (GLRLM) from the region of interests (ROIs) in ultrasound images. Three feature selection models, i) Sequential Forward Selection, ii) Sequential Backward Selection, and iii) F-score, are adopted to determine the identification of these liver diseases. Finally, the developed system can classify HCC and liver abscess by SVM with the accuracy of 88.875%. The proposed methods can provide diagnostic assistance while distinguishing two kinds of liver diseases by using a CAD system.