Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor impairment with various implications on patients’ quality of life. Since currently available therapies are only symptomatic, identifying individuals with prodromal, preclinical or early-stage PD is crucial, as they would be ideal candidates for future disease-modifying therapies. Our analysis aims to develop a robust model for accurate PD detection using accelerometer data collected from PD and non-PD individuals with mild or no tremor during phone conversations. An open-access dataset comprising accelerometer recordings from 22 PD patients and 11 healthy controls (HC) was utilized. The data were pre-processed to extract relevant time, frequency and energy-related features, and a Bidirectional Long Short-Term Memory (Bi-LSTM) model with attention mechanism was employed for classification. The performance of the model was evaluated using 5-fold cross-validation, and metrics of accuracy, precision, recall, specificity, and f1-score were computed. The proposed model demonstrated high accuracy (98%), precision (99%), recall (98%), specificity (96%), and f1-score (98%) in accurately distinguishing PD patients from HC. Our findings indicate that the proposed model outperforms existing approaches and holds promise for detection of PD with subtle symptoms, like tremor, in the wild. Such symptoms can present in the early or even prodromal stage of the disease, and appropriate mobile-based applications may be a practical tool in real-life settings to alert individuals at risk to seek medical assistance or give patients feedback in monitoring their symptoms.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Polymer electrolyte was used as a medium for testing the performance of microband electrodes under conditions of linear diffusion. Cyclic voltammetry and chronoamperometry experiments were performed in such viscous medium, where diffusion rates are much slower than in fluid solutions. Confirmation of the existence of such conditions from the log i vs. log v or log i vs. log t relationships in the current equation always yielded values lower than the expected value of 0.5. This could indicate impure linear diffusion profile, i. e. some contribution from radial diffusion (edge effect). However, performing these tests in monomeric solvents of similar viscosities, such as glycerol or propylene glycol, gave the desired value of 0.5. These results lead to the conclusion that current equations which are based on Fick’s laws may not be applicable for polymer electrolytes, where various obstruction to diffusion make it a more complicated process than in monomeric solvents.

A wide variety of pump and treat methods like chemical precipitation, adsorption, ion exchange and reverse osmosis have been trialled for many decades for fluoride removal from groundwater, but the problem of fluoride contaminated water remains in many parts of the world largely because these processes require constant monitoring, are expensive to implement and maintain at decentralised scale due to lack of reticulation infrastructure, and possess sludge disposal problem. This paper presents an overview of various fluoride removal processes and the limitations associated with each process and the application of in-situ permeable reactive barrier for remediating fluoride contaminated groundwater is explored, which displays the potential to be a cost effective, low maintenance and energy intensive technology.

Plagiarism means taking another person’s work and not giving any credit to them for it. Plagiarism is one of the most serious problems in academia and among researchers. Even though there are multiple tools available to detect plagiarism in a document but most of them are domain-specific and designed to work in English texts, but plagiarism is not limited to a single language only. Bengali is the most widely spoken language of Bangladesh and the second most spoken language in India with 300 million native speakers and 37 million second-language speakers. Plagiarism detection requires a large corpus for comparison. Bengali Literature has a history of 1300 years. Hence most Bengali Literature books are not yet digitalized properly. As there was no such corpus present for our purpose so we have collected Bengali Literature books from the National Digital Library of India and with a comprehensive methodology extracted texts from it and constructed our corpus. Our experimental results find out average accuracy between 72.10 % - 79.89 % in text extraction using OCR. Levenshtein Distance algorithm is used for determining Plagiarism. We have built a web application for end-user and successfully tested it for Plagiarism detection in Bengali texts. In future, we aim to construct a corpus with more books for more accurate detection.

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

The Double U-pipe ground heat exchanger, recognized for its straightforward process, cost-effectiveness, high heat exchange efficiency, and low thermal resistance, stands as the predominant ground heat exchanger type in today's shallow geothermal energy development and utilization. Recent years have seen significant research into the heat transfer influencing factors and heat exchange performance of Double U-pipe ground heat ex-changers via experimental testing methods. Yet, studies integrating numerical simulation with in-situ testing have been less frequent. Drawing on the cylindrical heat source model theory and the outcomes of regional in-situ thermal response tests, this paper develops a Double U-pipe ground heat transfer model by establishing physical, mathematical, and heat transfer geometric models. It assesses the impact of varying inlet temperatures, flow rates, and initial ground temperatures on heat exchange efficiency under heating conditions. The results validate the precision of the double U-pipe ground heat exchanger model based on in-situ testing. They show that enhancing the temperature differential between the inlet and initial temperatures, elevating the initial ground temperature, and moderately increasing the flow rate can boost the system's heat exchange efficiency.

Fall detection systems play a crucial role in addressing the significant health concern of elderly falls, a leading cause of health deterioration and mortality. As the aging population grows and life expectancy increases, the development of accessible tools becomes vital for predicting and preventing falls, offering a practical and widely applicable solution in contrast to costly and expertise-dependent assessment tools. In contrast, due to the formidable challenges encountered, a comprehensive investigation into the comparative performance of standard ML models within this field still needs to be explored. This paper proposes a standard pipeline for pre-processing, training, and evaluating ML models for fall detection on the SisFall dataset. We conducted extensive experiments to evaluate the performance of various ML models for fall detection. The results validate the efficiency of the deep model in identifying the time windows in which a fall occurred. Among the deep models, the architecture, including a combination of convolutional neural networks and fully connected layers, outperforms the others by macro-averaged Precision, macro-averaged Recall, and macro-averaged F1-Score of 87.03\%, 86.83\%, and 86.93\%, respectively.

Environmental DNA (eDNA) sampling has emerged as a powerful approach for monitoring biodiversity in the context of diverse terrestrial and aquatic ecosystems, and has broad potential for both environmental surveys and species management. eDNA studies focusing on plant and animal species have capitalized on analytical methodologies developed originally for metagenomic studies of microorganisms, and on technological improvements in sample collection. However, while eDNA studies have proliferated rapidly, efforts to standardize sampling and analytical methods are still nascent. Critically, fundamental data concerning the distribution and persistence of eDNA in different ecological contexts are lacking, complicating both confidence in species detection and comparability between studies. We propose that key deficits could be addressed by using well-designed synthetic DNA standards or tracers, which are widely used in fields ranging from medical diagnostics to hydrology. In-field application of a standardized mixture of barcoded synthetic DNA fragments of varying lengths and concentrations that are recovered concommitantly with eDNA sampling should provide critical yet missing data on environmental DNA distribution and turnover, as well as an internal molecular standard to enhance both species detection and comparability between eDNA studies.

Spatial biology is a rapidly growing research field which focuses on the transcriptomic or proteomic profiling of single cells within tissues with preserved spatial information. Imaging-based spatial transcriptomics uses epifluorescence microscopy, which has shown remarkable results for identification of multiple targets in situ. Nonetheless, the number of genes that can be reliably visualized is limited by the diffraction of light. Here, we investigate the effect of structured illumination (SIM), a super-resolution microscopy approach, over the performance of single gene transcript detection in spatial transcriptomics experiments. We performed direct mRNA-targeted hybridization in situ sequencing for multiple genes in mouse coronal brain tissue sections. We evaluated spot detection performance in widefield and confocal images versus those with SIM in combination with 20X, 25X and 60X objectives. In general, SIM increases the detection efficiency of gene transcripts spots compared to widefield and confocal modes. For each case, the specific fold increase in localizations is dependent on gene transcripts density and the numerical aperture of the objective used, which showed to play an important role especially for densely clustered spots. Taken together, our results suggest that SIM has the capacity to improve spot detection and overall data quality in spatial transcriptomics.

Current commercial, pre-commercial, and experimental in ovo techniques for the sex determination of fertilised eggs employ either minimally invasive biomolecular assays (extracting fluid via a small laser-drilled window in the eggshell, for detection of genetic or hormonal biomarkers), analysis of volatile compounds emitted from the eggshell, visible imaging, and reflectance or transmission spectroscopic analysis exploiting molecular optical fluorescence, polarisation, and scattering phenomena, including various combinations of these modalities. , to date no endeavour employing the NIR and FTIR based spectroscopic techniques has resulted in a commercially sustainable solution to the egg sexing problem. Besides achieving only subpar performance in overall accuracy, specificity, and sensitivity, the least invasive of the current state-of-the-art optical methods still requires, creating a transmission window (fenestration) of 12–15 mm diameter through to the mammillae layer of the shell, proximal to the external shell membrane, which can affect the incubation or post-hatch development viability of up to 10% of incubated eggs. Multimodal solution combining Raman spectroscopy and hyperspectral imaging has strong prospects to overcome the hard barriers existing before the perfection of a non-invasive in-line process for high reliability and rapid throughput for sex determination of eggs within 3 days of incubation. The method for sexing of chicken embryos needs to take a multipronged approach in collecting and analyzing spectral data that points to biomarkers using the machine learning approaches to look for nanomolar to picomolar concentrations of these in the fluid.

The assessment of concrete structures' durability in chlorine environments is significantly impacted by the uncertainty inherent in existing durability models. It introduce an integrated approach for updating these models, based on detection information of existing structures. This approach narrows the gap between theoretical predictions and observed structural durability. Specifically, we refine the probability model of critical chloride content by analyzing steel bar corrosion sample proportions, using Bayesian theory for greater accuracy. The enhanced model enables more reliable life expectancy prediction, forming a solid foundation for maintaining and strengthening existing structures.This method was demonstrated through a case study of a reinforced concrete industrial building with a service life of 12 years.

In recent times, the process control network (PCN) of oil and gas installation has been subjected to amorphous cyber-attacks which include Denial-of-Service (DoS), Distributed-Denial-of-Service (DDoS), Man-in-the-Middle (MitM) attacks, and this may have been caused majorly by the integration of open network to Operation Technology (OT) as a result of low-cost network expansion. The connection of the OT to the internet for firmware updates, third-party support, or vendor interventions, has exposed the industry to attacks. The inability to detect these unpredictable cyber-attacks exposes the PCN and a successful attack can lead to devastating effects. This paper reviews the different forms of cyber-attacks in PCN of oil and gas installations and proposes the use of machine learning algorithms to monitor data exchanges between the sensors, controllers, processes, and the final control elements on the network so as to detect anomalies in such data exchanges. Python 3.0 Libraries, Deep-Learning Toolkit, MATLAB, and Allen Bradley RSLogic 5000 PLC Emulator software were used in the simulation of process control. The outcome of the experiments shows the reliability and functionality of the different machine-learning algorithms in detecting these anomalies with significant precise attack detections identified using a coarse tree algorithm.

The presented results of simulations take into account the optical parameters of the selected sea region (from literature data on the southern Baltic Sea) and two optically extreme types of crude oil (from historical data) which exist in the form of a highly diluted oil-in-water emulsion (10 ppm). The spectral index was analyzed based on the results of modelling the radiance reflectance distribution for almost an entire hemisphere of the sky (zenith angle from 0 to 80o). The spectral index was selected and is universal for all optically different types of oil (wavelengths 650 and 412 nm). The possibility of detecting pollution in the conditions of the wavy sea surface (as a result of wind of up to 10 m/s) was studied. It has been also shown that if the viewing direction is close to a direction perpendicular to the sea surface, observations aimed at determining the spectral index are less effective than observation under the zenith angle of incidence of sunlight for all azimuths excluding the direction of sunlight specular reflection.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.

That how to improve the sensitivity and the detection ability of the Large-caliber sensor is critical to satisfy the requirement of heavy vehicle wear condition monitoring. In this paper, we introduced the LC resonance principle to the design of sensor with large flow channel (7mm). The resonant exciting coil increases the impedance change of the exciting circuit caused by wear particles which magnify the current difference between the two exciting coils and improve the sensitivity of the sensor. The resonant induction coil greatly suppresses the interference signals and magnifies the weak induced electromotive force which is beneficial to enhance the detection ability. In order to boost the detectability for different materials particles, a phase controlled variable-frequency exciting system (PCVFES) was adopted to automatically switch the exciting frequency between 284kHz for ferromagnetic particles and 420KHz for non-ferromagnetic particles. For the weak signal detection, based on the essential characteristic of the signal, we apply a simpler method that modified lock-in amplifier (MLIA) rather than the conventional algorithms (Wavelet transform, EMD). Results show that using these methods the sensitivity and the detection ability of the sensor are significantly improved and the 75μm iron particles and 220μm copper particles were successfully detected which realizes the initial abnormal wear monitoring for the large flow project.

With Internet of Things (IoT) gaining presence throughout different industries a lot of new technologies have been introduced to support this undertaking. Implications on one such technology, wireless systems allowed for the use of different communication methods to achieve the goal of transferring data reliably, with more cost efficiency and over longer distances. Anywhere from a single house with only a few IoT devices such as a smart light bulb or a smart thermostat connected to the network, all the way to a complex system that can control power grids throughout countries, IoT has been becoming a necessity in everyday lives. This paper presents an overview of the devices, systems and wireless technologies used in different IoT architectures (Healthcare, Vehicular Networks, Mining, Learning, Energy, Smart Cities, Behaviors and Decision Making), their upbringings and challenges to this date and some foreseen in the future.

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in the current study. In situ hybridization detected SAV3 in the heart, pseudobranch, gills, pyloric caeca, and pancreas after virus infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus at different adipose tissues associated with the internal organs of the salmon, suggests a specific affinity of SAV3 to adipocyte’s components. The innate immune response to SAV3 in the pseudobranch after infection dominated over the adaptive responses, yet it did not mitigate the infection in that tissue. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon.

In this paper, we discuss major issues of mathematics teaching and learning in Nepal. The issues coming from theories such as social and radical constructivism suggest that teachers are not trained to use such approach in teaching mathematics, and there is a lack of teaching aids and materials and technological tools. The issues related to social aspects are gender issues, language issues, social justice issues, and issues related to the achievement gap. The cultural issues are related to the diversity of language and ethnicity. The issues related to political aspects are equity and access, economic status, pedagogical choice, and professional organizations and unions. The issues related to technology include the technological skills, use of technology, and affordance. Finally, we suggest that all the stakeholders should pay attention to resolving these issues by improving the curriculum, training teachers, resourcing the classroom with locally made and new technological tools.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

The food system, the most important driver of planetary transformation, is in a deep crisis. Therefore, seeking a sustainable and socially-fair transition pathway becomes an issue of utmost priority for our own survival. The consideration of food as a commodity, a social construct that played a central role in driving this crisis, remains the uncontested narrative to lead the different transition pathways what seems rather contradictory. By exploring the normative values in the transition landscape, this paper seeks to understand how relevant is the hegemonic narrative of “food as commodity” and its alternative of “food as commons” to determine transition trajectories and food policy beliefs. Applying the Multi-level Perspective framework and developing the ill-studied “agency in transition”, this research enquired food-related professionals that belong to an online community of practice (N=95) on valuation of food dimensions and agency in food transitions to check whether the valuation of food is relevant to explain personal stances in transition. Results suggest the socially-constructed view of food as commodity is positively correlated to the gradual reforming attitude, whereas food as commons is positively correlated to the counter-hegemonic transformers regardless the self-defined position in the transition landscape (regime or niches). At personal level, there are multiple loci of resistance with counter-hegemonic attitudes in varied institutions of the regime and the innovative niches, many of them holding this discourse of food as commons. Conversely, alter-hegemonic attitudes are not positively correlated to this alternative discourse and they may inadvertently or purportedly reinforce the ‘‘neoliberal narrative’’. Food as commons, a different narrative whose rationale is explained in the paper, seems to be a relevant framework that could enrich the multiple transformative constituencies that challenge the industrial food system and therefore facilitate the convergence of movements that reject the commodification of food.

This study presents a methodology to reveal traces of viral particles, as aerosol with known chemical and molecular structure, in a sample by means of photon and electron interactions. The method is based on Monte Carlo simulations and on the analysis of photon-electron fluxes-spectra through energy channels counts as a function of different aerosol viral concentrations in the air sample and looking at the peculiar photon/electron interactions with the potential abnormal atomic hydrogen (H), oxygen (O), carbon (C), and phosphorus (P) compositions present in the air sample as a function of living and nonliving matter with PO4 group RNA/DNA strands in a cluster configuration.

In the context of improving aircraft safety, this study focuses on the development and evaluation of a graphene-based ice detection system using an environmental chamber. The research is driven by the need for more accurate and efficient ice detection methods, crucial in mitigating in-flight icing hazards. The methodology employed involves testing flat graphene-based sensors in a controlled environment, simulating a variety of climatic conditions that could be experienced in an aircraft during its entire flight. The environmental chamber enabled precise manipulation of temperature and humidity levels, thereby providing a realistic and comprehensive test bed for sensor performance evaluation. The results were significant, revealing the graphene sensors’ heightened sensitivity and rapid response to the subtle changes in environmental conditions, especially the critical phase transition from water to ice. This sensitivity is the key to detecting ice formation at its onset, a critical requirement for aviation safety. The study concludes that graphene-based sensors, tested under varied and controlled atmospheric conditions, exhibit a remarkable potential in enhancing ice detection systems for aircraft. Their lightweight, efficient and highly responsive nature makes them a superior alternative to traditional ice detection technologies, paving the way for more advanced and reliable aircraft safety solutions.

Based on the geochemical analysis of the volcanic material from the sediment core AMK-340, central zone of the Reykjanes Ridge, we could detect two ash-bearing sediment units accumulated during the Termination I. They correlate to the Ash Zone I in the North Atlantic Late Quaternary sediments having an age of 12170-12840, within the Younger Dryas cold chronozone, and 13600-14540 years, within and Bølling-Allerød warm chronozone. The ash of the Younger Dryas unit is presented mostly by the mafic and persilicic material originated from the Icelandic volcanoes; Vedde Ash is presented in one sediment sample from this unit. The ash of the Bølling-Allerød unit is presented mostly by the mafic shards which are related to the basalts of the rift zone on the Reykjanes Ridge, having presumably the local origin. A detection of Vedde Ash helped to specify the timing of the previously reconstructed paleoceanographic changes for the Termination I in the point of study: a significant warming in the area could occur as early as 300 years prior to the end of the conventional Younger Dryas cold chronozone.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance. Thereby, forcing the evolution of the teaching model to the virtual classroom. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico, during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p<0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress and compulsive checking). Our results further showed that the perceived stress and anxiety, fell into the category of absent to mild with only the danger section of the ACSS falling into the moderate category. Finally, resilience generated throughout the quarantine, seems to be a predictor of the adaptation the academic professional has undergone to cope with stress.

Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions and ecosystem functions. Endemics and CoEs play a prominent role in nature conservation monitoring and management, and in the organization of zoos, aquaria and botanical gardens. We review the meaning of different groups of organisms and indicators for the characterization of endemic-rich regions, the importance of heterogeneity in space, continuity in time, isolation and ex-situ management for the survival of endemic and threatened species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species concentrated in CoEs. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides or tsunamis. For conservation purposes the management of zoos, aquaria, botanical gardens, of regional land use, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of biodiversity, which is linked with human culture including the management of zoos, aquaria and botanical gardens, aesthetics, wellbeing, health and trade.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumour can be categorized into two main groups: in situ and infiltrative, with the latter being the most common malignant lesions. The current use of Magnetic Resonance Imaging (MRI) was shown to provide highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a Computer-Aided Detection/Diagnosis (CAD) system that could provide valuable assistance to the radiologist for the discrimination between in situ and infiltrating tumours. The system consists of two main processing levels: 1) Localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter) followed by a deep-feature extraction and classification method for false-positive rejection; 2) Characterization of the selected ROIs and discrimination between in situ and invasive tumour, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70.

In recent years, pedestrian re-identification has gained a lot of interest due to its importance for many purposes such as security and safety. Many types of solutions have been proposed to solve this problem, where the majority are based on a features extraction such Convolution Neural Networks (CNNs). These approaches assume that only the identities that are in the training data can be recognized. The pedestrians in the training data are called In distribution (ID). However, in real world scenarios, new pedestrians and objects can appear in the scene and the model should detect them as Out Of Distribution (OOD). In our previous study , we proposed a pedestrian re-identification based on von-Mises Fisher (vMF) distribution. Each identity is embedded in the unit sphere as a compact vMF distribution far from other identities distributions. The embedding is done through a base CNN. Recently, proposed a framework called Virtual Outlier Synthetic (VOS), that detects OOD based on synthesising virtual outlier in the embedding space in an online manner. Their approach assumes that the samples from the same object maps to a compact space. This assumption aligns with the vMF based approach. Therefore, in this paper, we revisited the vMF approach and merged with VOS in order to detect OOD data points. We present our approach to merge both frameworks. We conducted several experiments to evaluate our proposed framework. Results showed that our framework was able to detect new pedestrian that do not exist in the training data in the inference phase. It also slightly helped to improve the re-identification performance.

The Oxford English Dictionary includes 17 definitions for the word “model” as a noun and other 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For in-stance, “model railways” refer to replicas of railways and trains at a smaller scale and a “model student” refers to an exemplar individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning of a model. Even if the context is narrowed, specifically to the research related to the tumour microenvironment, a “model” can be understood in a wide variety of ways, from an animal model, to a mathematical expression. This paper presents a review of the different “models” of the tumour microenvironment grouped by the different def-initions of the word into four categories: model organisms, in vitro models, mathematical models, and computational models. Then, the frequency of different meanings of the word “model” related to the tumour microenvironment is measured from the number of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequency of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, in particular xenografts and mouse models are the most common used “models”, the number of entries have been slowly de-creasing. Mathematical models, prognostic and risk models follow in frequency and these have been growing in use.

Policies are adopted and implemented to achieve specific goals. In this regard, the Government of Zambia in 2019 adopted the higher education policy with many objectives which include, the expansion of access to higher education; reduction of gender and other forms of inequity in accessing higher education; the improvement of quality of higher education by increasing funding to higher education institutions, construction, and repair of infrastructure in higher and improvement in the provision of learning materials in higher education institutions (HEIs).This paper, therefore, sought to evaluate the higher education policy of 2019. The four criteria were used namely; effectiveness, equity, policy sustainability, and consistency. Other principles such as political and social acceptability of a policy were not used because the policy is already adopted and being implemented. Further, the principle of efficiency was not used because it would have been problematic to gauge the expenditure against the outcomes.The findings have revealed that the policy to some extent has been effective; some of the objectives such as increased access to higher education and reduction of inequality have been partially achieved. It has been established that the number of students pursuing higher education has been increased to 114,049 in 2020 from 91,969 in 2017. Further, in 2021, 48.5% of scholarships in public universities were awarded to female students while 51.5% were awarded to female students. Further, more students are encouraged to pursue science, technology, engineering, and mathematics (STEM); and more women are pursuing studies in STEM-related fields. However, the policy has not helped to achieve the quality of higher education as funding in public HEIs has not improved. Further, infrastructure remains very poor and inadequate; and access to update and relevant learning materials also remains a challenge in HEIs. However, the policy seems to be duplicated by the recent re-launched Technical Education Vocation Entrepreneurship Training (TEVET) national policy.Given the above findings, it has been recommended that the government among other things improve funding and build infrastructure in public HEIs. There is also a need to harmonise the TEVET national policy with the higher education policy.

Detecting suicidal ideation in adults with major depression is crucial for timely intervention and prevention of self-harm. As suicide is influenced by various biological, socio-cultural and psychological factors, traditional screening methods have accuracy and efficiency limitations. In certain cultures, societal stigma and marginalization can compel individuals with depression to conceal their suffering. Such individuals often turn to online social media platforms and share their experiences with peers under the protection of anonymity. Our research explored the potential of machine learning detection of suicidal ideation among Romanian adults with major depression that contributed to a web-based depression support forum. A trained algorithm (C4.5 decision tree) analyzed 125 posts fed to on a free access online support forum over 5 years (2014 – 2018) and classified them based on suicidal ideation content. 32 texts (25%) were identified as having a high probability of suicidal ideation content. 65% of the authors were male, with a mean age of 36.7±10.3 years and an average duration of illness of 3.4±1.4 years. Texts indicating positive suicidal ideation were generally shorter and elicited more general responses but fewer professional responses compared to those without suicidal ideation content. The study's main limitations include the relatively small number of classified texts, the absence of prospective information and the lack of qualitative evaluation of the excerpts' content. As socio-demographic and linguistic actuarial results were comparable to data reported by real life studies, we may consider basic text mining techniques as a screening tool that is able to detect suicidal ideation in texts written in unstructured Romanian language.

An abdominal aortic aneurysm (AAA) is usually asymptomatic until rupture, which is associated with extremely high mortality. Consequently, early detection of AAAs is of paramount importance in reducing mortality; however, most AAAs are detected by medical imaging incidentally. The aim of this study was to investigate the feasibility of machine learning-based pulse wave (PW) analysis for the early detection of AAAs using a database of in silico PWs. PWs in the large systemic arteries were simulated using one-dimensional blood flow modelling. A database of in silico PWs representative of subjects (aged 55, 65 and 75 years) with different AAA sizes was created by varying the AAA-related parameters with major impacts on PWs – identified by parameter sensitivity analysis – in an existing database of in silico PWs representative of subjects without AAA. Then, a machine learning architecture for early detection of AAAs was proposed, which was trained and tested using the new in silico PW database. The parameter sensitivity analysis revealed that the AAA maximum diameter and stiffness of the large systemic arteries were the dominant AAA-related biophysical properties that significantly influence the PW. The simulated PW indexes extracted from the database showed that the PW was not only influenced by the presence of an AAA but was also significantly affected by multiple cardiovascular parameters that compromised the detection of AAAs by using individual PW indexes. Alternatively, the trained machine learning model performed well in classifying normal and AAA conditions using digital photoplethysmogram PWs from the database. These findings suggest that machine learning-based PW analysis is a promising approach for AAA screening using PW signals acquired by wearable devices.

The aim of this study is to solve the problems of complicated pretreatment and high analytical cost in the detection technology of trace drug toxicants in municipal wastewater. A high-performance magnetic sorbent was synthesized for enrichment of trace drug substances in wastewater to develop magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical methods for the molecules in wastewater drug toxicants. The magnetic nanospheres was successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinyl pyrrolidone.The results showed that the linear dynamic range of 17 drugs was 1-500 ng/L, the recovery was 43%-105%, the matrix effect was more than 67%, the limit of quantitative detection was 1-2 ng/L, and the detection time of each sample was 2.98s. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problem of complicated pre-treatment and analytical cost in the detection of drugs in wastewater. The developed magnetic material and acoustic excitation coupled mass spectrometry analysis method can realize the low-cost, efficient enrichment and fast analysis of different kinds of drug molecules in urban sewage.

Background &amp; Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between Dec 1st, 2017, and May 1st, 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid, surgical, and hospitalization-free treatment. Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p=0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p=0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p=0.593). Conclusion: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drug, food, water treatment and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity and (epi)genotoxicity. Also, new technologies, such as organ-on-chip and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of how from the production to final disposition chain of nanomaterials is evaluated under Life Cycle Assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review we give an overview of all these elements of nanosafety.

Knowledge of permafrost’s ice and unfrozen water content is critical for predicting the permafrost behavior during ice–water–ice transition. This is especially relevant when ice and permafrost are melting in many regions under the influence of global warming. It is well-known that only a part of the formation's pore water turns into ice at 0 ^oC. After the further lowering the temperature, the water phase transition continues, but at gradually decreasing rates. Thus, the porous space is filled with ice and unfrozen water. The laboratory data show that frozen formations' mechanical, thermal, and rheological properties strongly depend on the moisture content. Hence, porosity and temperature are essential parameters of permafrost. In this paper, it is shown how, and by combining research in three fields: (1) geophysical exploration, (2) numerical modeling, and (3) temperature logging, it is possible to estimate in-situ the porosity of permafrost. To demonstrate the procedure, five examples of numerical modeling (where all input parameters are specified) are given. This investigation is the first attempt to analyze the permafrost’s porosity in situ quantitively.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

The domain of Information and Communication Technology (ICT) education has garnered significant consideration in recent times. However, several challenges are inherent to this area of study, including monetary expense, temporal factors, pedagogical environment, teacher training programs, incentive, syllabus design, and health-related concerns. This paper presents an analysis of the difficulties encountered in the realm of ICT education in Japan, taking into account ten different perspectives.

The effect of the melt cooling rate on the atomic ordering of austenite and, as a consequence, on the martensitic transformation of a nonstoichiometric alloy of the Ni-Mn-In system has been studied. In-situ TEM observations revealed differences in the mechanism of phase transformations of the alloy subjected to different cooling conditions. It is shown that during quenching a high density of antiphase boundaries (APB) is formed and the alloy is in the austenite-martensitic (10M and 14M) state up to a temperature of 120K. In a slowly cooled alloy, a lower APB density is observed, and a two-stage transformation L21/B2 → 10M → 14M occurs in the range of 150–120 K.

The main objective of this research was to analyze the relationship between socioeconomic and demographic indicators and the level of transparency of municipalities in the state of Maranhão. The transparency index was constructed based on the LRF and LAI and consisted of 32 items. Subsequently , for To identify which factors explain the level of transparency, a multiple linear regression was carried out, comparing the explanatory variables for the level of transparency adopted in this study. The sample consisted of municipalities in the State of Maranhão, totaling 211 municipalities, as 7 did not have a website. The results of the multiple linear regression model indicate that the IDHM, the log of total GDP, the GDP per capita and the variable log of POP explain the NT of the municipalities surveyed to the point of explain the level of transparency of the municipalities of Maranhão, only the IFDM did not show a relationship with the NT among the variables analyzed.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Leukemia, contributing to 3% of all cancer cases in the United States, presents a significant challenge in treatment due to its diverse subtypes, each dis-playing unique genetic and molecular abnormalities. The aggressive growth of ab-normal blood cells compromises immune function and poses challenges in developing effective therapeutic approaches. Unlike solid tumors, surgical resection is not an option, limiting treatment strategies to chemotherapy, immunotherapy, and radiation therapy, which may be nonspecific and lead to organ damage and toxicity. Anthracyclines, widely used in hematological tumors, face limitations due to severe cardiotoxicity, causing progressive cardiomyopathy and, in severe cases, congestive heart failure. Heart failure incidence is significantly higher in cancer patients treated with anthracyclines over 5, 10, and 15 years. Early detection of left ventricular dysfunction and cardiotoxicity is crucial to mitigate progression to congestive heart failure (CHF) in this population. Recent research by Bayrón-Marrero et al. reveals that lower levels of plasma soluble TREM-Like Transcript-1 (s-TLT-1), a platelet-specific receptor, correlate with left ven-tricular dysfunction in cardiovascular disease patients. Those with s-TLT-1 levels ex-ceeding 544 pg/mL exhibit a significant association with congestive heart failure. These findings suggest the potential use of s-TLT-1 as a diagnostic screening tool for early detection and treatment of anthracycline-induced CHF in leukemia patients.

The development of mineral resources in China has gradually entered the stage of deep mining. Rock burst, collapse and other ground pressure disasters caused by deep high stress have become major hidden dangers restricting mine safety production. Microseismic monitoring technology is an important means of ground pressure risk prediction. In this paper, the wavelet coefficient threshold denoising method in time-frequency domain, STA/LTA method, AIC method, Skew and Kurtosis method are studied, and the automatic P-phase onset time picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized. the reliability of the P-phase onset time picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity underground mine, Which is of great significance to the data processing and analysis of microseismic monitoring.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Current article presents the study of psychological wellbeing of adolescents (n=168, age 15-17) gifted in math, humanities and sports and educated in advanced programs for gifted children. Theoretical framework of this study is eudemonic concept of psychological wellbeing by C. Ryff. Psychological wellbeing is measured with Ryff wellbeing scales in Russian adaptation by L.V. Zhukovskaya and E.G. Troshikhina. The study is aimed at understanding differences in psychological wellbeing of gifted teenagers connected to gender and type of giftedness. The results suggest that general wellbeing score did not differ for adolescents with different types of giftedness or of different genders. Separate components of psychological wellbeing, such as purpose in life and self-acceptance, are influenced by activity connected to the talent. Gender differences are subjected to age-specific trends of personal development in adolescence. Type of giftedness might reinforce these trends.

This research paper examines the effects, advantages, challenges, and economic aspects of a research town. The study concludes that inclusion and diversity not only constitute fundamental values but also serve as crucial drivers of business success and sustained competitiveness. Universities play a central role in shaping the prosperity of the research town by functioning as knowledge hubs, fostering collaboration, nurturing talent, and contributing to the broader innovation ecosystem. The symbiotic relationship between universities and industries within the cluster establishes a dynamic and resilient environment for research and development. The presence of startups within the research cluster introduces novel ideas, enhancing the overall vibrancy and competitiveness of the local economy. In an era where social media algorithms increasingly influence people's choices, the potential for foreign interference emerges as a significant threat.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

In the last decade, unprecedented progress in the development of neural networks influenced dozens of different industries, among which are signal processing for the electroencephalography process (EEG). Electroencephalography, even though it appeared in the first half of the 20th century, to this day didn’t change the physical principles of operation. But the signal processing technique due to the use of neural networks progressed significantly in this area. Evidence for this can serve that for the past 5 years more than 1000 publications on the topic of using machine learning have been published in popular libraries. Many different models of neural networks complicate the process of understanding the real situation in this area. In this manuscript, we provided the most comprehensive overview of research where were used neural networks for EEG signal processing.

Membrane Inlet Mass Spectrometry (MIMS) was used to analyze monochloramine solutions (NH₂Cl) and ammonia solutions in a compact FTICR. Chemical ionization enables identification and quantification of the products present in the permeate. The responses of protonated monochloramine and ammonium increase linearly with the solution concentration. The enrichments were respectively 1.2 and 5.5. Pervaporation is dependent on pH and only the basic form of ammonia NH₃ pervaporates through the membrane. Unexpectedly, the small ammonia molecule permeated very slowly. It could be due to interactions with water molecules inside the membrane that create clusters. Moreover, NH₂Cl solutions, in addition to the NH₃Cl⁺ signal, presented a strong NH₄⁺ signal at m/z 18.034 . Ammonia presence in the low-pressure zone before ionization is probable as NH₄⁺ was detected with all the precursors used, particularly CF₃⁺ and trimethylbenzene that presents a proton affinity higher than monochloramine. Ammonia may be formed inside the membrane due to the fact that NH₂Cl is unstable and may react with the water present in the membrane. Those results highlight the need for caution when dealing with chloramines in MIMS and more generally with unstable molecules.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Background: Redo mitral valve surgery is the standard of care for failed mitral bioprostheses or recurrence of mitral regurgitation after repair. Nonetheless, catheterbased valve-in-valve (ViV) or valve-in-ring (ViR)-procedures increasingly become viable alternatives in high risk subpopula-tions. Despite reported good initial results, only little is known about longer-term outcomes. The present series report long-term outcomes of transcatheter mitral ViV- and ViR-procedures. Methods: All consecutive patients (n=54) undergoing transcatheter mitral ViV- or ViR-procedures for failed bioprostheses or recurring regurgitation after mitral repair were retrospectively en-rolled in the time period between 2011 and 2021. The mean age was 76.5 ± 6.5 years, and 30 (55.6%) of the patients were male. The procedures were done using a commercially available balloon-expandable transcatheter heart valve. Clinical and echocardiographic follow-up data were obtained out of the hospital’s database and analyzed. Follow-up reached up to 9.9 years with a total of 164.3 patient-years. Results: A total 25 patients received a ViV- and 29 patients a ViR-procedure. Both groups were at high surgical risk with an STS-PROM of 5.9 ± 3.7 % in ViV- and 8.7 ± 9.0% in ViR-patients, respectively (p<0.01). The procedures itself were mainly unevent-ful with no intraoperative deaths and a low conversion rate (n=2/54; 3.7%). VARC-2 procedural success was low (ViV 20.0% and ViR 10.3%; p=0.45), which was either driven by high rates of transvalvular pressure gradients “>5mmHg” (ViV 92.0% and ViR 27.6%; p<0.01) or residual regurgitation “>trace” (ViV 28.0% and ViR 82.7%; p<0.01). ICU-stay was prolonged in both groups (ViV 3.8 ± 6.8 days and ViR 4.3 ± 6.3 days; p=0.96) with acceptable hospital stay (ViV 9.9 ± 5.9 days and ViR 13.5 ± 8.0 days; p=0.13). Despite 30-days mortality was acceptable (ViV 4.0% and ViR 6.9%; p=1.00), the mean posthospital survival time was disappointingly low (ViV 3.9 ± 2.6 years and ViR 2.3 ± 2.7 years; p<0.01). Overall survival I the entire group was 33.3%.Cardiac reasons for death were frequent in both groups (ViV 38.5% and ViR 52.2%). Cox-regression analysis identified ViR-procedures as a predictor of mortality (HR 2.36, CI 1.19 - 4.67, p=0.01). Conclusions: Despite acceptable immediate outcomes in this high-risk subpopulation, long-terms results are discouraging. Transvalvular pressure gradients as well as residual regurgitations remained drawbacks in this real-world population. The indication for catheterbased mitral ViV- or ViR-procedures thoughtfully must be made in consideration of conventional redo-surgery or conservative treatment.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

The non-structural protein (NS) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NS and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at NSs1-32, NSs56-82, and NSs207-237. Rationally, three mutant NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NS. Over-expression of wild-type NS in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NS-NP interaction and viral replication. Thus, the present study identified a critical NS site, which could be targeted for development of therapeutic regimens against SFTSV.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets.

This work focuses on the study of the microstructure, hardening and stiffening effect caused by the secondary phases formed in titanium matrices. These secondary phases were originated from reactions between the matrix and boron particles added in the starting mixtures of the composites. Not only was the composite composition studied as an influencing factor in the behaviour of the composites, but also different operational temperatures. Three volume percentages of boron content were tested (0.9, 2.5 and 5 vol % of amorphous boron). The manufacturing process used to produce the composites was inductive hot pressing, which operational temperatures were between 1000 °C to 1300 °C. Specimens showed optimal densification. Moreover, microstructural study revealed the formation of TiB in various shapes and proportions. Mechanical testing confirmed that the secondary phases had a positive influence on the properties of the composites. In general, adding boron particles increased the hardness and stiffness of the composites; however rising temperatures resulted in greater increases in stiffness than in hardness.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

In this paper, a proof similar to the Pusey-Barrett-Rudolph (PBR) theorem is given to prove that time in quantum theory is not epistemic but has ontological reality. For this, we first discuss how time can be encoded as an intrinsic property of a quantum system. We prepare a quantum state containing time as an intrinsic property and show by a PBR-type proof that time cannot be an epistemic notion. In fact, the PBR theorem implies an ontic notion of time. Indeed, if the quantum state is a physical property, then quantum state reduction is a physical process involving information destruction. In this case, quantum probabilities are intrinsic probabilities without epistemic origin, and they generate a genuinely new sequence of events. This novelty introduced by quantum probabilities can be interpreted as time.

In this study, we have first studied the trend in meteorological data from the Harmaleh, Vanai and Farsesh stations in the 50-year period in the Dez catchment area. The meteorological data will be then forecasted using SWAT and Mann-Kendall. Forecasting the results in the Mann-Kendall and SWAT model has been done using the code written in MATLAB software and RCP (4.5, 8.5) scenarios, respectively. Studying the results of the trend in the data of meteorological stations in this catchment area indicated that these two parametric and non-parametric methods have been used to determine trends in meteorological data. The results of the parametric method are positive in all meteorological parameters. Non-parametric method over a period of 50 years shows the presence of trends in the data. The comparison on the forecasting results at maximum temperature suggested that during summer, we will see an increase in temperature compared to the ground state in all three forecasts. The results of the minimum temperature forecast show a decrease in the minimum increase during the winter and the precipitation forecast indicates that at the end of autumn (Nov) precipitation decreased by 20 mm in the Mann-Kendall and 4.5 RCP while RCP8.5 suggests the increase in precipitation compared to the ground state. Studying the runoff forecast results using SWOT show that at the end of winter (Feb) and almost all spring (Mar, Apr) a decrease of about 40%, 15% and 14% will be seen, respectively

This study investigated whether metabolomic fingerprints of bovine embryo growth media improve the prediction of successful embryo implantation. In this prospective cohort study, the metabolome from in vitro produced Day 7 blastocysts with successful implantation (n=11), blas-tocysts with failed implantation (n=10), and plain culture media without embryos (n=5) was in-cluded. Samples were analyzed using AbsoluteIDQ® p180 Targeted Metabolomics Kit with LC-MS/MS, and a total of 189 metabolites were analyzed from each sample. Blastocysts that re-sulted in successful embryo implantation had significantly higher levels of methionine sulfoxide (p<0.001), DOPA (p<0.05), spermidine (p<0.001), acetylcarnitine to free carnitine ratio (p<0.05), C2+C3 to free carnitine ratio (p<0.05), and lower levels of threonine (nep<0.001) and phosphati-dylcholine PC ae C30:0 (p<0.001) compared to control media. However, when compared to embryos that failed to implant, only DOPA, spermidine, C2/C0, (C2+C3)/C0 and PC ae C30:0 levels differentiated significantly. In summary, our study identifies a panel of differential metabolites in the culture media of bovine blastocysts that could act as potential biomarkers for the selection of viable blastocysts before embryo transfer.

Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.

Diabetes mellitus is a global health issue that necessitates the development of novel therapeutic approaches. Today numerous experimental methods have been used and set up to evaluate novel drugs with antidiabetic effects. In addition, several research studies have been done to induce diabetes under in vitro and in vivo conditions, but only a small number of these efforts are currently in a usable stage. This review aims to provide useful guidance for researchers who seek to evaluate the antidiabetic potential of drugs, agents, or new medications using the standard methods published by authorities and academics worldwide organizations and research centers. In this review, we collected 132 relevant articles from prominent databases such as PubMed, ScienceDirect, Scopus and others to summarize in vitro and in vivo experimental validation of antidiabetic treatment from 1943 to present.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a ‘laboratory’ case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.

In article 16 of the United Nations Convention (UN), or the United Nations Convention on the Rights of the Child (UNCRC), which is usually called the Convention on the Rights of the Child, outlines the right of every child to privacy and protection against violations of privacy related to the home. , family, communication, and their good name. Children's privacy, especially when it comes to personal data, requires strict boundaries. Current digital developments influence children's parenting and thinking patterns with potential negative impacts. Children can be targets of abuse in the digital world. Children's personal data is often used until they become independent. This research, using normative legal methods, aims to analyze regulations related to the protection of children's personal data in the digital era. Therefore, updates are needed in the laws and regulations governing children's personal data to safeguard their privacy rights in accordance with the UNCRC.

The objective of this research is to analyze the effect of determinants of Business ethics (HR management ethics, ethics in corporate governance, and ethics in sales & marketing) on the organizational performance of the high-tech industry. The study further examines the influence of multiple serial mediations of human, structural, structural, and relational capital on the connection between Business ethics and organizational performance. Additionally, this research examines how technological change moderates the relationship between Business ethics and organizational performance. Data was collected from the information technology sector in various cities of South Asian countries through structured questionnaires. PLS-SEM modeling was used via Smart-PLS 4.0 software for analysis. The hypothesized & modified measurement and structural model were validated using the HTMT matrix, Fornell-Larcker criterion, R-square values, f-square values, outer loading, construct reliability and validity, path coefficient analysis, Blindfolding, and predictive relevance. The research results suggest that ethics in corporate governance, HR management ethics, and ethics in sales & marketing have a notable positive effect on business ethics, leading to a substantial and affirmative impact on the organizational performance of the high-tech industry. The findings further suggested that dimensions of intellectual capital (human capital, structural capital & relational capital) significantly moderate between exogenous and endogenous constructs. Moreover, technological change significantly & positively moderates the relationship between Business ethics and organizational performance of the high-tech industry. In conclusion, this research provides insights into how these variables interact and what potential mechanisms act upon them. Organizations can make informed decisions about improving their performance and ethical standards by understanding these relationships. This research offers substantial theoretical and managerial implications to research scholars and industry practitioners.

This study investigated how positive (e.g., incentives) and negative (e.g., restrictions) reinforcement used in vaccination promotional messages and trust in government impact parental vaccine perceptions and decisions on vaccinating their children during a large-scale infectious disease crisis. Two hundred and eighty-six parents of unvaccinated teens participated in a 2 (reinforcement: positive vs. negative) × 2 (trust in government: high vs. low) between-subjects experimental survey. Positive reinforcement (e.g., gift cards for the vaccinated) was more effective for parents with low trust in the government to improve their attitudes and intentions toward child vaccination, while parents with high trust in the government were unaffected by reinforcement types. To the best of our knowledge, this study is among the first to examine the effects of both positive and negative reinforcement on vaccination perceptions and behavioral intentions through a controlled experiment and is the first study to do so in a large-scale infectious disease crisis setting. This research is expected to help public health professionals better prepare for and manage virus-induced public health crises in the future.

Blended learning, the integration of online and face-to-face instruction, has garnered attention in education. This paper aims to explore challenges in blended learning faced by students, teachers, and parents and propose mitigating strategies. The study employed qualitative research methods and involved 30 participants from St. Michael's College. Findings revealed primary challenges, including technical difficulties, time management, lack of interaction, and varying digital literacy levels. These challenges influenced engagement, communication, and student achievement. The study utilized a theoretical framework encompassing Technological Pedagogical Content Knowledge, Social Presence Theory, and Activity Theory. Strategies recommended comprise providing technical support, promoting communication and collaboration, offering professional development, and leveraging learning analytics. The study contributes to the existing literature by identifying specific challenges and proposing practical recommendations for enhancing blended learning effectiveness. Limitations include a small sample size and context-specific findings. Future research should investigate these challenges in broader settings and examine the long-term effects of the recommended strategies. Addressing blended learning challenges can empower educators, administrators, and policymakers to create supportive and effective learning environments for all stakeholders involved.

The classical propositional calculus (zero-order logic, classical propositional logic), is the most fundamental two-valued logical system. In this paper we present a proof of inconsistency of the classical propositional calculus. Then, we get right away the conclusion that the metatheory of the classical propositional calculus is inconsistent.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The study used various techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to characterize the particles and their interactions with proteins. Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Moreover, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particles resulted in general the least toxic. Furthermore, the study found that at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

Analyzed the literature devoted to the changes in the expression of the RAS proteins of cancer cells. A brief review of protein expression dynamics PAC in malignant tumors and the possible role of epigenetic mechanisms in these processes. Through research epigenetic mechanisms state for cancer have been developed principally new techniques for their correction, based on the use of selective regulators systems covalent modification-histone proteins (for example, deacetylase inhibitor) and microRNA synthesis technologies. Literature data show promising pharmacological correction epigenetic modification of chromatin in the treatment of cancer.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Parents’ attitudes and practices may support the children’s reactions to treatments for leukemia and their general adjustment. This study has two aims: to explore parenting depending on child's age and to develop and test a model on how family processes influence the psycho-social development of children with leukemia. Patients were 118 leukemic children and their parents recruited at the Haematology-Oncologic Clinic of the Department of Pediatrics, University of Padua. All parents were Caucasian with a mean age of 37.39 years (SD = 6.03). Children’s mean age was 5.89 years (SD = 4.21). After the signature of the informed consent, the parents were interviewed using the EFI-C from which we derived Parenting dimension and 3 parental perceptions on child’s factors. One year later, the clinical psychologist interviewed again parents using the VABS scales. The analyses revealed the presence of a significant difference in parenting by child’s age: Infants required a higher and more intensive parenting. Child’s coping to medical procedures at the second week after the diagnosis, controlled for parenting effect, impacted upon child’s adaptation one-year post diagnosis. Specific intervention programmes are proposed in order to help children more at risk just after the diagnosis for developmental delays.

In this work, we designed a MEMS device which allows simultaneous direct measurement of mechanical properties during deformation under external stress and characterization of the evolution of microstructure of nanomaterials within a transmission electron microscope. This MEMS device makes it easy to establish the correlation between microstructure and mechanical properties of nanomaterials. The device uses piezoresistive sensors to qualitatively measure the force and displacement of nanomaterials, e.g., in wire and thin plate forms. The device has a theoretical displacement resolution of 0.19 nm and a force resolution of 2.1 μN. The device has a theoretical displacement range limit of 2.74 μm and a load range limit of 27.75 mN.

This article explores the relationship between convex functions defined on integers ($\mathbb{Z}$) and their extension to real numbers ($\mathbb{R}$). We introduce key definitions and investigate the hypothesis that there exists a unique convex curve within this family of functions, leading to a proof by contradiction. Our findings highlight the preservation of convexity as functions transition from integers to real numbers.

Among the alternatives pointed out as able to make livestock a more efficient activity and reduce its environmental impact, the use of feeds with high digestibility and the use of non-conventional fodder species can be highlighted. Tithonia diversifolia (Hemsl.) A. Gray (TD) has already gained attention as a feed for ruminants. Nonetheless, there has been little discussion about the impacts of this plant on the rumen dynamics that lead to better animal performance. The aim of this study was to assess how increasing levels of TD could affect ruminal microbial biomass synthesis, degradability, and in vitro gas production (IVGP) of diets. Four diets were evaluated: a control diet (TD0: 400 g kg-1 soybean meal and corn grain, and 600 g kg-1 Tifton 85 hay (Cynodon spp)) and three increasing levels of TD (TD9: 90, TD27: 270, and TD45: 450 g kg-1 – dry matter basis) as a replacement for dietary roughage. A 96-hour IVGP assay was carried out and five incubation times (2, 4, 10, 24, and 96 hours) were used for degradability determination. Gas produced, methane (CH4), degradability of organic matter (IVDOM), short-chained fatty acid (SCFA) production, partitioning factor (PF), and microbial biomass (MB) were evaluated among treatments. There was no significant effect (P&gt;0.05) between TD inclusion and IVGP at most incubation times; only at 6 hours of incubation did gas production increase linearly with TD inclusion (R2=0.19; P&lt;0.05). TD inclusion had no effects on CH4. IVDOM increased linearly with TD inclusion at 6 and 10 hours, with TD45 being more degradable than the control diet at 6 hours only. There was a positive linear relationship (R2=0.20; P&lt;0.05) between TD inclusion and PF. TD45 had significantly higher PF values than the control. MB also increased linearly (R2=0.30; P&lt;0.05) with TD inclusion, and all diets with TD had significantly more MB than the control diet. The inclusion of TD at the levels used in this work was revealed to have a positive impact on microbial protein synthesis, which could be related to the higher microbial efficiency of increased substrate quality.

The out-of-time-ordered correlation (OTOC) function is an important new probe in quantum field theory which is treated as a significant measure of random quantum correlations. In this paper, with the slogan "Cosmology meets Condensed Matter Physics" we demonstrate a formalism using which for the first time we compute the Cosmological OTOC during the stochastic particle production during inflation and reheating following canonical quantization technique. In this computation, two dynamical time scales are involved, out of them at one time scale the cosmological perturbation variable and for the other the canonically conjugate momentum is defined, which is the strict requirement to define time scale separated quantum operators for OTOC and perfectly consistent with the general definition of OTOC. Most importantly, using the present formalism not only one can study the quantum correlation during stochastic inflation and reheating, but also study quantum correlation for any random events in Cosmology. Next, using the late time exponential decay of cosmological OTOC with respect to the dynamical time scale of our universe which is associated with the canonically conjugate momentum operator in this formalism we study the phenomena of quantum chaos by computing the expression for {\it Lyapunov spectrum}. Further, using the well known Maldacena Shenker Stanford (MSS) bound, on Lyapunov exponent, λ≤2π/β, we propose a lower bound on the equilibrium temperature, T=1/β, at the very late time scale of the universe. On the other hand, with respect to the other time scale with which the perturbation variable is associated, we find decreasing but not exponentially decaying behaviour, which quantifies the random correlation at out-of-equilibrium. Finally, we have studied the classical limit of the OTOC to check the consistency with the large time limiting behaviour.

Turning ships in port turning basins is an important and responsible operation, mainly involving the ship itself and the port tugs. Such operations involve many maneuvers that consume a lot of energy (fuel) and emit a lot of emissions. Turning basins in harbors and quay approaches are in most cases relatively shallow. The paper examines the turning of ships in port turning basins using harbor tugs, the effect of shallow depth on ship turning, energy (fuel) consumption and the generation of emissions during such maneuvers of harbor tugs. The paper presents the developed theoretical models, and the experimental results on theoretical models, which were verified on real ships and using calibrated simulators. Discussions and conclusions prepared on the basis of the research base. The use of the developed methodology makes it possible to increase shipping safety, optimize maneuvers and reduce energy (fuel) consumption when turning ships in the port and at the same time reduce the amount of fuel consumed by port tugs and reduce the number of emissions of tugs during such operations.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

Gentiopicroside (GPS) is a leading component of several plant species from Gentianaceae botanical family. As a compound with plenty biological activities and a component that is often consumed in dietary supplements and herbal drugs, GPS has an important role in the regulation of physiological processes in humans. Recent studies on the type 2 receptors shed new light on GPS applications showing its agonistic properties that could be meaningful in the future therapeutic strategies of Parkinson’s disease, thyroid disorders or cancer states. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention at the newly discovered role of this bitter-tasting secoiridoid as a type 2 receptor agonist. Thanks to these properties, the research on this substance could be revisited.

In an increasingly interconnected world, the internationalization of languages plays a pivotal role in shaping global linguistic landscapes. This qualitative study delves into the intriguing realm of Cebuano, a language with a rich cultural heritage and a vibrant community of speakers. Through a meticulous exploration of language variation, adaptation, and policy dynamics, the researcher unravels the complex interplay between Cebuano and the global linguistic tapestry. Drawing upon a comprehensive literature review and qualitative research, including in-depth interviews and focus group discussions, this paper illuminates the nuanced manifestations of Cebuano beyond its traditional borders and sheds light on its presence in diverse international settings. The findings reveal the intricate dance of language and identity, offering insights into the processes of language maintenance, shift, and revitalization. As the researcher navigates the multifaceted dimensions of Cebuano's internationalization, not only is its global significance unraveled, but also the intricate connections between language, culture, and human experience are investigated. This study not only contributes to the scholarly discourse on language dynamics but also raises compelling questions about the preservation of linguistic diversity, the power of language in shaping identities, and the role of language in fostering intercultural understanding. By embracing the kaleidoscope of Cebuano's global journey, this paper invites readers to contemplate the broader implications for language diversity, communication, and cultural preservation in an increasingly interconnected world.

Every country has some specific heraldry. In this paper, we will consider heraldry in the Republic of Macedonia, understood by the multitude of coats of arms, and armorial knowledge and art. The paper covers the period from independence until the name change (1991-2019). It covers the state coat of arms of the Republic of Macedonia especially the 2009 change. Special attention is given to the development of the municipal heraldry, including the legal system covering the subject. Also personal heraldry developed in 21 century is considered. The paper covers the development of heraldry and the heraldic thought in the given period, including the role of the Macedonian Heraldic Society and its journal Macedonian Herald in development of theoretic and practical heraldry, as well as its Register of arms and the Macedonian Civic Heraldic System.

The stimulus-secretion coupling of glucose-induced release is generally attributed to the metabolism of the hexose in the β-cells in the glycolytic pathway and the citric acid cycle. Glucose metabolism generates an increased cytosolic concentration of ATP and of the ATP/ADP ratio that closes the ATP-dependent K+-channel at the plasma membrane by the interaction of ATP with the regulatory Kir6.2 channel subunit The resultant depolarization of the β-cells opens voltage-dependent Ca2+-channels at the plasma membrane that allow an increase of the cytosolic cation concentration that triggers the exocytosis of insulin secretory granules. The resultant secretory response evolves in time as a biphasic secretion with a first and transient peak of approximately 10 minutes duration followed by a sustained phase of secretion lasting as long as the stimulus. Whereas the first transient peak can be reproduced by a simple depolarization of β-cells with high extracellular KCl maintaining the KATP-channels open with diazoxide, the sustained phase is agreed to depend on the participation of some metabolic signal that remains to be determined Our group has been investigating for several years the participation of β-cell GABA metabolism, together with that of glucose (the β-cell “specific” nutrient secretagogue) and some other “metabolic” secretagogues (branched-chain alpha-ketoacids and a mixture of L-Leucine + L-glutamine, at supraphysiological concentrations) in their mechanism of stimulation of insulin secretion. All three types of stimuli promote the flux in the GABA shunt of rat islets by different metabolic pathways that end in the production of α-ketoglutarate. This citric acid cycle intermediary is preferentially derived to the GABA shunt instead of its continuous oxidation in the citric acid cycle. Islet content of GABA is significantly suppressed by all the stimuli and blocking the GABA shunt with gabaculine, or ϒ-vinyl-GABA (GABAT inhibitors), diminish the insulin secretory responses as well as total ATP and the ATP/ADP ratio. It is concluded that GABA metabolism is increased in parallel to glucose metabolism and is significantly contributing to the magnitude of the insulin secretory response. Its possible implication in β-cells degradation in type-2 (perhaps also in type 1) diabetes is suggested.

Sugarcane mosaic virus (SCMV) is a deleterious pathogen which causes widespread Sugarcane mosaic disease (SCMD) and is classified in the genus Potyvirus (Potyviridae), disseminated by the aphid vector. RNA interference (RNAi)-mediated antiviral innate immunity is a key biological process and antiviral defence system to interfere with viral genomes for controlling plant pathogens. The current study aims to analyze sugarcane (Saccharum officinarum L. and Saccharum spp.) locus-derived microRNAs (sof-miRNAs/ssp-miRNAs) with predicted potential for targeting the SCMV +ssRNA-encoded mRNAs, using ‘five algorithms’ approach. The ultimate goal in this research is to mobilize the in silico endogenous predicted sof-miRNAs/ssp-miRNAs to trigger RNAi catalytic pathway experimentally and generate sugarcane cultivars for evaluating potential antiviral resistance monitoring capability and capacity for SCMV. Experimentally validated mature sugarcane (S. officinarum, 2n = 8X = 80) and (S. spp., 2n = 100-120) sof-miRNAs/ssp-miRNAs (n = 28) were acquired for alignment with the SCMV genome. Of the 28 targeting mature locus-derived sof-miRNAs/ssp-miRNAs investigated, one sugarcane miRNA homolog, sof-miR159c, was concluded to localize potential binding site at genomic nucleotide site 3847 targeting CI ORF of SCMV. In order to validate target prediction accuracy, whether the sugarcane sof-miRNA/ssp-miRNA might bind predicted SCMV mRNA target(s), we created an integrated Circos plot. Genome-wide in-silico-predicted miRNA-mediated target gene regulatory network validated interactions that warrant in vivo analysis. The current work provides valuable evidence and biological material for generating SCMV-resistant sugarcane varieties.

Listeria ivanovii and L. monocytogenes, are the only pathogenic species of the genus Listeria and share many virulence factors and mechanisms of pathogenicity. L. ivanovii shows host tropism towards small ruminants and rodents and much lower virulence for humans compared to L. monocytogenes. However, severe infections caused by L. ivanovii, resulting in bacteremia, abortion and stillbirth, occasionally occurred in immunocompromised persons and in pregnant women, while in immunocompetent hosts L. ivanovii can cause gastroenteritis. In this review the updated knowledge on virulence aspects and distribution of L. ivanovii in the environment and in food are summarized. Recent research on its virulence characters at genome level gave indications on how pathogenicity evolved in this bacterial species. As for L. monocytogenes, L. ivanovii infections occur after the ingestion of contaminated food, so an overview of reports regarding its distribution in the food products was carried out to obtain indications on the categories of foods exposed to contamination by L. ivanovii. It was found that a wide variety of food products can be a source of this microorganism and that, like L. monocytogenes, L. ivanovii is able to persist in the food production environment. Studies on its ability to grow in enrichment and isolation media suggested that its occurrence in nature might be underestimated. Moreover, virulence varies among strains for differences in virulence character regulation, presence/absence of genetic regions and the possible instability of a Listeria pathogenicity genomic island, LIPI-2, which is unique to L. ivanovii. We can conclude that L. ivanovii, as a possible pathogen for animals and humans, requires more focused investigations regarding its occurrence in the environment and in food and on intra-species variability of pathogenic potential.

Background: This study addresses the burgeoning impact of Large Language Models (LLMs) such as ChatGPT on the integrity of online examinations and seeks to demonstrate latent and advanced LLM reasoning capabilities. The research devises an iterative self-reflective strategy for invoking critical thinking and higher-order reasoning in LLMs based on multimodal exam questions using visuals and text. Methods: The proposed strategy was demonstrated and evaluated on real exam questions by subject experts and the performance of ChatGPT (GPT-4) with vision was estimated on an additional dataset of 600 text descriptions of multimodal exam questions, focusing on its response to complex, visual, and textual prompts. Results: The results indicate that latent multi-hop reasoning capabilities can be invoked using the proposed self-reflective strategy, which can effectively steer ChatGPT towards correct answers by integrating critical thinking from each modality into the final response. Meanwhile, ChatGPT demonstrated considerable proficiency in being able to answer multimodal exam questions across 12 subjects. Conclusions: This work challenges findings from recent studies which claim that existing LLMs are unable to reason on complex multimodal tasks, and therefore this study underscores the need for enhanced online exam security measures like proctoring software, that can mitigate the potential misuse of AI technologies in educational settings.

In this paper, we propose a new mathematical model based on the association between susceptible and recovered individual, where the association between susceptible and recovered individual is disturbed by white noise. This model is based on demographic changes and is used for long term behavior. We study the stability of equilibria of the deterministic model and prove the conditions for the extinction of diseases. Then, we investigate and obtain the critical condition of the stochastic epidemic model for the extinction and the permanence in mean of the disease with the white noise. To verify our results, we present some numerical simulations for real data related to disease.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments many times lacking efficiency and leading to severe side-effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150.4 ± 3.7 nm) and homogeneous (PDI of 0.162 ± 0.008) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models, with GI50 values between 12.37 ng/mL and 14.72 ng/mL. Additionally, they also revealed substantial anti-inflammatory activity, with an IC50 of 28.98 ng/mL, effects that have been reported to be complementary to direct antitumor activity. Finally, the niosomes' safety was assessed, both in vitro, on skin, liver and kidney cells, and ex vivo, in a HET-CAM assay, and results showed that compound encapsulation increased its safety. Hence, small and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies.

Considering the ever-increasing role of rare-earth elements (REE) in the modern hi-tech field, their effective use has a tremendous significance, although the production process is inevitably linked to the large volumes of industrial ammonia effluents and heavy metal wastes. In the process of metallurgical separation of metals, the emission of large volumes of noxious gases and radioactive substances is inevitable. Lean technogenic raw material processing is sensible under the condition of the development of non-waste technology. The lack of competent regulations governing the disposal of waste containing REE has an impact on adjacent territories, accumulating in water bodies and, as a result, in the human body. Such an impact cannot pass without a trace, however, the ambiguity of opinions in the scientific community regarding the toxic effects of REE on living organisms determines the relevance of a more detailed study of this issue. The paper presents experimental and theoretical results of studies of ion flotation in the aqueous solutions containing ytterbium cations and a surfactant as a collector - sodium dodecyl sulphate (NaDS).

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

Software-In-The-Loop (SITL) simulation tools have been extensively used in development of safety-critical software. Utilizing these tools substantially accelerates software development eliminating potential risks and resource costs of physical experiments. This paper investigates the effects of model specific parameters on the development and testing of custom module in PX4 SITL environment. Models of a fixed-wing unmanned aerial vehicle with vertical takeoff and landing capabilities and steerable sensor platform/gimbal are used as case study for this investigation. The effects of parameters of these aerial vehicle and sensor platform models are taken into consideration in the development of custom module that controls the dynamics of steerable sensor platform mounted on the vehicle model. The work also presents steps necessary to customize PX4 SITL and Gazebo simulation environment to incorporate parameters of the vehicle and sensor platform models in the development and testing process of custom module. Based on these instances, simulation results are obtained and discussed. The results show that reliability of PX4 SITL simulation framework is justified by proper customization and integration of PX4 SITL and Gazebo simulator.