During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

Background: The study aimed to explore the association between the prognostic nutrition index (PNI) and in-hospital complication and mortality in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We conducted a retrospective analysis using data from the Changhua Christian Hospital Clinical Research Database (CCHRD) between January 2015 and December 2022. 2402 patients were included, with the median PNI value set at 42.77. The restricted cubic spline model, Kaplan-Meier and ROC analysis for overall survival were used to evaluate the association of PNI with medical complications and mortality. Propensity score matching (PSM) analysis was performed to balance these clinical variables between groups, which could reduce potential bias to some extent. Results: PNI was significantly associated with in-hospital complications and 28-day and 90-day mortality in multivariate analysis. The main finding of our study is that a low PNI score at admission was independently associated with a poor ICH outcome. The Kaplan-Meier curves revealed higher survival rates in the high PNI group. PNI demonstrated sensitivity to predict medical complications and mortality based on ROC analysis. Conclusions Our study suggests that PNI could serve as a valuable marker for predicting medical complications and mortality in patients with spontaneous ICH.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

Sanctuaries devoted to Asclepius were established and operated for almost a thousand years in various Greek and Roman cities throughout the Mediterranean region. The Asclepieion sanctuary in Lenta (formerly known as Ancient Lebena) in Crete was famous for receiving water from a sacred spring. In the Ancient Lebena, Levinaion was a famous centre for hydrotherapy, physiotherapy and a psychiatric hospital. In the present paper, we aim to assess the hydrochemical status of this sacred spring that holds a prominent position in archaeological and historical studies. The main objectives of this study are: Initially, to present supervisory evidence (archaeological, geological, hydrochemical) of an area that was a water resource management model for many centuries, carrying out therapeutic work. The second objective is to present and compare hydrochemical data in the last century, i.e. from 1915 to 2021. The third objective is to highlight and warn of an incipient saltwater intrusion in the area along the Lentas coast. The fourth objective is to propose an alternative and sustainable form of water resources management in the region that requires the study and rational utilization of the sporadic small water springs in the region. Our study focuses on a basic hydrochemical analysis of spring and borehole water in the remains of Levinaion in the Lentas region and their comparison with spare historical data of the sacred spring water, aiming to interpret the impact of the changes in the spring water resources that occurred in the last decades due to urban modernization. Our results highlight (i) visible fluctuations in chemical composition of borehole water samples, (ii) a neutral to alkaline pH in borehole waters, and an alkaline pH in spring waters, (iii) un-detectable arsenic of Lentas borehole water, unlike historical data of Lentas spring water, (iv) low values of dissolved radon of Lentas borehole water and spring water of Kefalovrysa, and (v) a timeless constant and hypothermic nature of the water of both sacred spring and borehole of Lenta, but also of Kefalovrysa spring. The recorded historical data, i.e. from 1915 to 1957, due to the absence of substantial anthropogenic activity in the area, can be used as reference values (natural background levels, NBLs) for the Lentas area. Our findings emerge with the need to bring again the flowing spring water of the sacred spring of Lentas in its original form through sustainable management and re-discover its beneficial therapeutical effects.

We prove a quasi-pseudometric version of the strong Ekeland principle proved by P. Georgiev and T. Suzuki.

The chemical reaction of ion-adsorption type rare earth during in-situ leaching process is accompanied by ion migration and charge movement, making the leaching process electrochemical in nature. The chemical reaction rate plays an important role in the leaching rate of rare earth elements. In this work, electrochemical impedance spectroscopy (EIS) was used to reveal characteristics of electrical resistance alteration and leaching rate of rare earth elements during in-situ leaching. The equivalent circuit model of the leaching process was established, and two critical parameters of solution resistance Rs and charge transfer resistance Rt were analyzed to reflect the electrochemical characteristics. According to the characteristics of electrical resistance alteration, the leaching process was divided into four stages: wetting, reaction, equilibrium, and top water stage. The resistance parameters Rs and Rt decreased first and then increased during the leaching process. The maximum value of Rs was 1330Ω∙cm2 at the end of the top water stage, and the minimum value was 135Ω∙cm2 at the beginning of the equilibrium stage. The maximum value of Rt was 8310Ω∙cm2 at the beginning of the leaching stage, and the minimum value was 21Ω∙cm2 at the end of the reaction stage. Rs and Rt were negatively correlated with the pore size and chemical reaction rate during leaching. With increasing of pore size and reaction rate , the resistance parameter decrease. This study provide a new idea for intelligent monitoring of rare earth ore.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during aerosolization of liquids or powders and the role of aerosol flow dynamics in RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Analyzing existing technical limitations, several potential strategies for enhancing the efficiency of targeted therapeutic delivery to or through the respiratory system are identified and presented, including the use of smart inhaling devices incorporating AI algorithms.

In order to reveal the frost heaving mechanism of void water behind the lining of high-speed railway tunnels in cold regions，the voids were first classified according to the positional relationship between voids and waterproof panels，and then the water supply and discharge conditions of different types of voids were investigated，then the influence of the excretion conditions on the frost heave force was experimentally studied. Based on these conditions，circular wedge-shaped and flying saucer-shaped void freezing models were established to analyze the evolution process of accumulated water frost heave. Then，according to the relative position of the excretion channel and the void，the excretion coefficient was introduced，and the calculation method of the frost heaving force of the voided water was proposed，and the influencing factors and laws of the frost-heave force were revealed. The results are shown as follows: 1) The blockage of the excretion channel will lead to the generation of frost heaving force; 2) The freezing and thawing process of the water within the cavity develops from the thinnest part of the void edge to the thicker part，and the process of frost heave-thaw，water replenishment-re-freeze heave of the water within the cavity leads to greater and greater frost heave force; 3) The frost-heaving force of the water within cavity is controlled by the void height and the position of the excretion channel. The larger the cavity height is or the closer the excretion channel is to the bottom surface of the void，the greater the frost-heave force is.

Artificial intelligence (AI)-based conversational models, such as ChatGPT, Microsoft Bing, and Google Bard, emerged as valuable sources of health information for the lay individuals. However, the accuracy of information provided by these AI models remains a significant concern. This pilot study aimed to test a new tool referred to as “CLEAR”, designed to assess the quality of health information delivered by AI-based models. Tool development involved a literature review on health information quality, followed by initial establishment of the CLEAR tool comprising five items that aimed to assess the following: completeness of content in response to the prompt, lack of false information, evidence support, appropriateness, and relevance of the generated content. Each item was scored on a 5-point Likert scale from excellent to poor. Content validity was checked by expert review of the initial items. Pilot testing involved 32 healthcare professionals using the CLEAR tool to assess content on eight different health topics deliberately designed with varying qualities. The internal consistency was checked using the Cronbach α. Feedback through the pilot test resulted in language modifications to improve the clarity of the items. The final CLEAR tool was used to assess health information quality generated through four different AI-based models in five different, yet common health topics. The AI models were ChatGPT 3.5, ChatGPT 4, Bing, and Bard, and the content generated was scored by two independent raters with Cohen κ to assess the inter-rater agreement. The final five CLEAR items were: (1) Is the content sufficient? (2) Is the content accurate? (3) Is the content evidence-based? (4) Is the content clear, concise, and easy to understand? and (5) Is the content free from irrelevant information? Pilot testing using the eight different health topics revealed an acceptable internal consistency with a Cronbach α range of 0.669–0.981. The use of the final CLEAR tool yielded the following average scores: Bing (mean=24.4±0.42), ChatGPT-4 (mean=23.6±0.96), Bard (mean=21.2±1.79), and ChatGPT-3.5 (mean=20.6±5.20). The inter-rater agreement revealed the following Cohen κ values: for ChatGPT-3.5 (κ=0.875, P<.001), ChatGPT-4 (κ=0.780, P<.001), Bing (κ=0.348, P=.037), and Bard (κ=.749, P<.001). The CLEAR tool is a brief yet helpful tool that can aid to standardize testing of the quality of health information generated by the AI-based conversational models. Future studies are recommended to validate the utility of the CLEAR tool to assess the quality of the AI-generated health-related content using a larger sample across various complex health topics.

The radiation stability of polymer test objects fabricated by direct laser writing is studied. The two groups of 6 cubes (50×50×50 μm3) were printed on a common silicon substrate. 6 cubes were irradiated with X-rays in the synchrotron radiation beam (12 keV, 1010 photons/mm2/s), the other 6 kept non-irradiated for the reference. In each group, the fabrication parameters (laser power and slicing step) were uniformly varied from cube to cube. Each irradiated cube was exposed with the dose of 1013 X-ray photons. The calibration of this dose in the radiological units (Gy) was carried out using the tissue-equivalent thermoluminescent detectors (TLD-800). The corresponding exposition dose was estimated as 30 kGy for each cube. The radiation effects were evaluated by Raman spectroscopy and by morphological changes observed with the raster electron microscope. The primary radiation effect appears in the essential increase of the polymerization degree with consuming carbon-carbon double bonds in favor of the polymer cross-linking. Only one cube of 6 has changed the size and shape due to this effect, while the others retained the initial shape. Morphological changes are connected with the improper fabrication parameters (laser power and slicing step). Properly fabricated objects withstand the X-rays of the synchrotron radiation beam.

The rising prevalence of autism internationally has been accompanied with an increased appreciation of the poorer mental health experienced by people with this condition and also of their family care-givers. In particular higher incidences of anxiety and depression are reported in high income nations and these conditions are likely to be under-recognised and under-reported in lower resourced regions or countries. Mainstream mental health services seem to be ill-equipped to respond adequately to the needs of autistic persons and their care-givers. This scoping review of 30 recently published literature reviews covering over 1,000 journal articles, summarises the insights and strategies that have been shown to promote the mental health and emotional wellbeing of autistic persons. In particular, a focus on family-centred, community-based supports is needed that aim to enhance social communication, extend social connections and promote an individual’s self-esteem, self-determination and social motivation. These low-cost interventions are especially pertinent in low resourced settings but they can be used internationally to prevent mental illness and assist in the treatment of anxiety and depression in autistic persons and their family carers. The priority is to focus on primary care responses with cross-sectoral working rather than investing in high-cost psychiatric provision.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retain. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the non-invasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes.

Abstract: rainfall is the main driver of soil erosion. With the daily rainfall, riverine flow discharge and sediment load in the upper Lianjiang River watershed from 1990 to 2020, extreme rainfall events were defined by the 95th percentile method and minimum event interval time (MIT), change trends and mutations of yearly rainfall, riverine flow discharge and sediment load were identified using the Mann-Kendall test, then the optimum lag response time and antecedent rainfall were investigated with the multiple linear regression. The results showed that (1) the sediment changed significantly and abruptly in 1995 due to the expansion of the garden land. (2) Compared with ordinary rainfall, extreme rainfall events explained more variations of riverine flow and sediment with a higher degree, and had a more significant effect on the lag time of runoff and sediment. (3) Garden land expansion in extreme rainfall scenarios resulted in longer lag times for runoff and sediment and decreased demand for antecedent rainfall with more pre-event time. Therefore, taking the rainfall event as a breakthrough, analyzing the antecedent rainfall and the lag response of riverine flow discharge and sediment load is conducive to revealing the response mechanism of riverine flow discharge and sediment load and improving the simulation accuracy of riverine flow and sediment under extreme rainfall condition, thus help for the soil erosion control under extreme rainfall.

Efficient thermal management of modern electronics requires the use of thin films with highly anisotropic thermal conductivity. Such films enable the effective dissipation of excess heat along one direction while simultaneously providing thermal insulation along the perpendicular direction. In this study, we investigate the thermal conductivity of bilayer graphene (BLG) sheets using non-equilibrium molecular dynamics, examining both in-plane and cross-plane thermal conductivities. The in-plane thermal conductivity of 10 nm × 10 nm BLG with zigzag and armchair edges at room temperature is found to be around 204 W/m.K and 124 W/m.K, respectively. The in-plane thermal conductivity of BLG increases with sheet length. For all sizes, BLG with a zigzag edge exhibits higher thermal conductivity than that of the armchair edge, with this difference becoming more pronounced as the lengths of the sheets increase. In addition, increasing temperature from 300 K to 600 K decreases the in-plane thermal conductivity of a 10 nm× 10 nm zigzag BLG by about 34%. Similarly, the application of a 12.5% tensile strain induces a 51% reduction in its thermal conductivity compared to the strain-free values. Armchair configurations exhibit similar responses to variations in temperature and strain, but with less sensitivity. Furthermore, the cross-plane thermal conductivity of BLG at 300 K is estimated to be 0.05 W/m·K, significantly lower than the in-plane results by approximately four orders of magnitude. The cross-plane thermal conductance of BLG decreases with increasing temperatures, specifically, at 600 K, its value is almost 16% of that observed at 300 K.

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

Transmembrane carriers of the Slc11 family catalyze proton (H+)-dependent uptake of divalent metal-ions (Me2+) such as manganese and iron - vital elements coveted during infection. Slc11 mechanism of high affinity Me2+ cell import is selective and conserved between prokaryotic (MntH) and eukaryotic (Nramp) homologs, though processes coupling the use of the proton motive force to Me2+ uptake evolved repeatedly. Adding bacterial piracy of Nramp genes spread in distinct environmental niches suggests selective gain of function that may benefit opportunistic pathogens. To better understand Slc11 evolution Alphafold (AF2)/Colabfold (CF) 3D predictions for bacterial sequences from sister clades of eukaryotic descent (MCb and MCg) were compared using both native and mutant templates. AF2/CF model an array of native MCb intermediates spanning the transition from outward open (OO) to inward open (IO) carrier. In silico mutagenesis targeting i) a set of (evolutionary coupled) sites that may define Slc11 function (putative synapomorphy), and ii) residues from networked communities evolving during MCb transition, indicate Slc11 synapomorphy primarily instructs Me2+-selective conformation switch which unlocks carrier inner gate, and contributes to Me2+ binding site occlusion and outer gate locking. Inner gate opening apparently proceeds from interaction between transmembrane helix (h) h5, h8 and h1a. MCg1 xenologs revealed marked differences in carrier shape and plasticity, owing partly to altered intramolecular H+-network. Yet, targeting Slc11 synapomorphy also converted MCg1 IO models to OO state, apparently mobilizing the same residues to control gates. But MCg1 response to mutagenesis differed, extensive divergence within this clade correlating with MCb-like modeling properties. Notably, MCg1 divergent epistasis marks emergence of the genus Bordetella-Achromobacter. Slc11 synapomorphy localizes to the 3D areas that deviate least among MCb and MCg1 models (either IO or OO) implying it constitutes a 3D network of residues articulating Me2+-selective carrier conformation switch which is maintained in fast evolving clades at the cost of divergent epistatic interactions impacting carrier shape and dynamics.

Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. In this study, researchers conducted structure-based in silico screening to identify natural compounds that could target the DNA-binding domain (DBD) of the FOXM1 protein. Through molecular docking analyses, identified Silybin B as a potential inhibitor of FOXM1, exhibiting strong interaction with the protein. MD simulations were performed to validate the binding stability of the FOXM1-Silybin B complex. The study provides valuable insights into the potential of Silybin B as a FOXM1 inhibitor and its ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based design strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.

The economical load dispatch problem is a critical concern in thermal power systems to ensure cost-effective operation. This paper conducts a comparative analysis between the Social Spider Algorithm (SSA) and Particle Swarm Optimization (PSO) for economical load dispatch in a 6-unit thermal power system with the integration of 11,000 plug-in electric vehicles (PEVs). Both SSA and PSO are population-based optimization techniques designed to minimize the overall fuel cost while satisfying the load demand by determining the optimal power output of each unit. SSA emulates the social behavior of spiders, while PSO simulates the collective intelligence of a swarm of particles. Performance evaluation of the algorithms considers power system data, such as unit fuel costs, minimum and maximum loads, and total load demand. The objective is to minimize fuel cost while meeting the load demand. Comparative analysis of SSA and PSO includes convergence speed, solution quality, and computational efficiency. Experimental results indicate that SSA outperforms PSO in achieving a more optimal and economical load dispatch solution for the 6-unit thermal power system. SSA demonstrates faster convergence and provides superior-quality solutions compared to PSO. This paper contributes to the field by highlighting SSA's effectiveness in achieving cost-efficient operation of thermal power systems. The findings suggest that SSA holds promise as an optimization technique for similar power system optimization problems, enhancing overall operational efficiency and reducing costs for thermal power plants.

(1) Background: Acute myocardial infarction in pregnancy (pAMI) is a rare event, often caused by non-classical factors rather than atherosclerosis. The management of pAMI poses unique chal-lenges as it requires considering both maternal and fetal well-being.; (2) Methods: We present the case of a 36-week pregnant woman who presented with antero-lateral ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock. To ensure comprehensive decision-making, an emergency Pregnancy Heart Team meeting was convened, comprising interventional cardi-ologists, gynecologists, and anesthesiologists. The team prioritized interventional treatment for pAMI and opted for primary percutaneous coronary intervention (PCI) due to the unstable ma-ternal condition.; (3) Results: The patient underwent primary PCI as the chosen intervention for pAMI. A rapid response gynecology team closely monitored the procedure and was prepared to intervene in case of irreversible hemodynamic compromise leading to cardiac arrest. A caesarean section was deemed necessary if cardiac activity was not restored within 4 minutes.; (4) Conclusions: Managing pAMI requires a multidisciplinary approach that balances the maternal and fetal well-being. In this particular case, the Pregnancy Heart Team decided to prioritize interventional treatment with primary PCI due to the unstable maternal condition. The presence of a closely monitored gynecology team ensured prompt action in case of complications.

The integration of spray drying and agglomeration offers significant advantages, such us continuous production with lower energy consumption. However, it is a knife-edge process with a narrow operating window and limited degrees of freedom that decide between successful agglomeration and fluidized bed blockage due to excessive moisture. In this contribution, factors influencing the spray-through agglomeration process of skim milk powder as a model system were investigated via a design of experiments. Three in-line monitoring methods were applied and tested to observe the most important parameters in the agglomeration process: product moisture and particle size distribution. Regarding the moisture content, a capacitive moisture sensor was calibrated with linear regression and a near-infrared sensor with partial least squares regression. Near-infrared spectroscopy was found to be the suitable method for determining moisture content, while the capacitive moisture sensor mainly provides information on the bulk density, the filling level or fluidization state in the fluidized bed. Additionally, particle size distribution data was extracted from the spectral data using in-line data of a spatial filter velocimetry probe in the fluidized bed. This opens the potential to monitor both parameters in real-time with a single non-invasive sensor.

Oral and parenteral delivery of first-line anticonvulsant Valproic cid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in brain. GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in human. HSPiP software predicted excipients with maximum possible miscibility of the drug. Based on GastroPlus and HSPiP program, various excipients were screened for experimental solubility study and prepared cationic nanoemulsions and respective gels for nasal to brain delivery. These were characterised for size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Result showed that in-vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively from both tablets (IR and SR) at 8 h using GastroPlus. The drug access to the portal vein was relatively predicted high in IR (115 mg) as compared to SR (82.6 mg). Plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime site of drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested suitable selection of excipients. The program recommended for nasal to brain delivery of the drug using cationic mucoadhesive product. The optimized stable CVE6 was associated with optimal size (113 nm), low PDI (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7 %w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. Penetration study executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6 which may be attributed to electrostatic interaction between mucosal membrane and nanoglobules. Thus, cationic nanoemulsion and respective mucoadhesive gel are promising strategy for delivery of VA to brain through intransal administration for the treatment of seizure and convulsion.

This study aims at better understanding the damage and fracture kinetics in flax fibres elements at both the unitary and bundle scales using an experimental setup allowing optical observation at high recording rate in the course of tensile loading. Defects issues from flax unitary fibre extraction are quantitated using polarized light microscopy. Tensile loading is conducted according to a particular setup adapted to fibres of 10 to 20 µm in diameter and 10 mm in length. Optical recording using high speed camera is performed during loading up to the failure at acquisition speed ranging from 108,000 to 270,000 frames per second. Crack initiation in polymer layers of fibre elements, propagation as well as damage mechanisms are captured. The results show different failure scenarios depending on the fibre element nature. In particular, fractured fibres underline either a fully transverse failure propagation or a combination of transverse and longitudinal cracking with different balances. Image recordings with high time resolution down to 3.7 μs suggest unstable system and transverse crack speed higher than 4 m/s and a slower propagation for longitudinal crack deviation.

This paper investigates the classical but yet intriguing question of modeling orthotropic RC floor systems endowed with lightening elements, by means of a uniform orthotropic slab, in order to describe accurately the building response under seismic loads. The simplified method, commonly adopted by engineers, based on the equivalence between the transverse stiffness of the RC elements of the real floor and those of the orthotropic slab is presented. A case study in which this simplified method is used is also provided. Then, an advanced finite elements (FE) based method to determine the elastic properties of the equivalent homogenized orthotropic slab is proposed. Based on the results obtained from the application of this method to a case study, a discussion on the adequacy of the simplified method is also provided.

Developing new energy is critical to China's green and low-carbon development. And the New Energy Demonstration City Policy (NEDCP) is a vital innovation policy that inspires the development of new energy. Is the NEDCP facilitating green and low-carbon development, if so, how? Employing unbalanced panel data from 2003 to 2017, the impact of NEDCP on green and low-carbon development was studied by using the "difference in difference" (DID) model. We find that this policy can take significantly role. After various robustness tests, our results are still valid. According to the heterogeneity analysis, non-resource and non-old industrial base cities have a greater positive impact from this policy. The mechanism analysis denotes that the positive policy effect works through upgrading the industrial structure and stimulating urban innovation. The substantial empirical evidence presented in this article supports the continued promotion and implementation of new energy demonstration cities.

Low pasture biomass production and fodder scarcity are among the major challenges affecting productivity of dairy cattle farms in Sri Lanka. As a potential solution to this, two Napier hybrid cultivars CO-5 and Sampoorna were recently introduced and a field experiment was conducted to evaluate their growth, dry matter production and nutritional composition during May to September 2020. Plant measurements and samples were collected at five harvest intervals (4, 6, 8, 10 and 12 weeks after planting), with the plant samples subjected to biomass and nutritional assessments. The number of tillers and leaf length differed (P=0.01) between the two cultivars at 4 weeks harvesting interval (HI) whilst number of leaves differed at 12 HI respectively. Dry matter yield increased (P=0.16) almost linearly whilst crude protein declined exponentially with CO-5 greater than Sampoorna (P=0.057; 9.3% vs 8.7%), with increasing harvesting intervals respectively. In-vitro Organic Matter Digestibility and In-vitro Metabolizable Energy contents were similar across weeks 4, 6 and 8 but then decreased. This study demonstrates that higher dry matter yields (12.54 t/ha) can be obtained by harvesting both cultivars at 12 HI, but from a nutritional perspective harvesting at 6 HI during Yala season of the year would be optimum for farmers.

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

Purpose: Hearing assistive technology (HAT) has been shown to be a viable solution to the speech-in-noise perception (SPIN) issue in children with autism spectrum disorder (ASD); however, little is known about its efficacy in tonal language speakers. This study compared sentence-level SPIN performance between Chinese children with ASD and neurotypical (NT) children and evaluated HAT use in improving SPIN performance and easing SPIN difficulty. Methods: Children with ASD (n=26) and NT children (n=19) aged 6-12 performed two adaptive tests in steady-state noise and three fixed-level tests in quiet and steady-state noise with and without using HAT. Speech recognition thresholds (SRT) and accuracy rates were assessed using adaptive and fixed-level tests, respectively. Parents or teachers of the ASD group completed a questionnaire regarding children’s listening difficulty under six circumstances before and after a ten-day trial period of HAT use. Results: Although the two groups of children had comparable SRTs, the ASD group showed a significantly lower SPIN accuracy rate than the NT group. Also, a significant impact of noise was found in the ASD group’s accuracy rate, but not in the NT group’s. There was a general improvement in the ASD group’s SPIN performance with HAT and a decrease in their listening difficulty ratings across all conditions after the device trial. Conclusion: The findings indicated inadequate SPIN in the ASD group using a relatively sensitive measure to gauge SPIN performance among children. The markedly increased accuracy rate in noise during HAT-on sessions for the ASD group confirmed the feasibility of HAT for improving SPIN performance in controlled laboratory settings, and the reduced post-use ratings of listening difficulty further confirmed the benefits of HAT use in daily scenarios.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

The present study was aimed at revealing the influence of the mechanical stress induced by water molecules adsorption on the composition of crystalline phases in the ZrO2–3mol%Y2O3-nanoparticles. Three basic methods have been used to determine the phase transition: neutron diffraction, Raman microspectroscopic scanning, and X-ray diffraction. The fact of phase-structural β → α transformation and the simultaneous presence of two polymorphic structural modifications (β is the phase of the tetragonal syngony and α of monoclinic syngony in nanosized particles (9nm)) under normal physical conditions was established by these methods. Satisfactory consistency was achieved between the results obtained using different techniques.

Recent developments in mid-infrared (MIR) spectroscopic ellipsometry enabled by quantum cascade lasers (QCLs) resulted in a drastic improvement in signal-to-noise ratio compared to conventional thermal emitter based instrumentation. Thus, it was possible to reduce the acquisition time for high-resolution broadband ellipsometric spectra from multiple hours to less than 1 second. This opens up new possibilities for real-time in-situ ellipsometry in polymer processing. To highlight these evolving capabilities we demonstrate the benefits of a QCL based MIR ellipsometer by investigating single and multilayered polymer films. The molecular structure and reorientation of a 2.5m thin biaxially oriented polyethylene terephtalate film is monitored during a stretching process lasting 24.5 s to illustrate the perspective of ellipsometric measurements in dynamic processes. In addition, a polyethylene/ethylene vinyl alcohol/polyethylene multilayer film is investigated at continuously varying angle of incidence ( 0∘ – 50∘) in 17.2 s, highlighting an unprecedented sample throughput for the technique of varying angle spectroscopic ellipsometry in the MIR spectral range. The obtained results underline the superior spectral and temporal resolution of QCL ellipsometry and qualify this technique as suitable method for advanced in-situ monitoring in polymer processing.

When you type” Iodine” in google scholar, you will end up with 2,200,000 articles that are titled with anything regarding iodine, except “what is it”. Here in this short note review, a summary of iodine that includes its origin, structure, types, sources, uses, concentration, toxicity, and iodine intake and how to measure it, was collected and infused in a nutshell.

For the better part of a century researchers across disciplines have sought to explain the crystallography of the elemental transition metals: hexagonal close packed, body centered cubic, and face centered cubic in a form similar to that used to rationalize the structure of organic molecules and inorganic complexes. Pauling himself tried with limited success to address the origins of transition metal stability. These early investigators were handicapped, however, by incomplete knowledge regarding the structure of metallic charge density. Here we exploit modern approaches to charge analysis to first comprehensively describe transition metal charge density. Then, we use topological partitioning and quantum mechanically rigorous treatments of kinetic energy to account for the structure of the density as arising from the interactions between metallic tetrahedra. We argue that the crystallography of the early transition metals results from charge transfer from the so called “octahedral” to “tetrahedral holes” while the face centered cubic structure of the late transition metals is a consequence of antibonding interactions that increase octahedral hole kinetic energy.

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

Cellular redox state is highly dynamic and delicately balanced between constant production of reactive oxygen species (ROS), and neutralization by endogenous antioxidants, such as glutathione. Physiologic ROS levels can function as signal transduction messengers, while high levels of ROS can react with and damage various molecules eliciting cellular toxicity. The redox state is reflective of the cell’s metabolic status and can inform on regulated cell-state transitions or various pathologies including aging and cancer. Therefore, methods that enable reliable, quantitative readout of the cellular redox state are imperative for scientists from multiple fields. Liquid-chromatography mass-spectrometry (LC-MS) based methods to detect small molecules that reflect the redox balance in the cell such as glutathione, NADH and NADPH, have been developed and applied successfully, but because redox metabolites are very labile, these methods are not easily standardized or consolidated. Here we report a robust LC-MS method for the simultaneous detection of several redox-reactive metabolites that is compatible with parallel global metabolic profiling in mammalian cells. We performed a comprehensive comparison between three commercial hydrophilic interaction chromatography (HILIC) columns, and we describe the application of our method in mammalian cells and tissues. The presented method is easily applicable and will enable the study of ROS function and oxidative stress in mammalian cells by researchers from various fields.

This paper contains a concise overview of the deployment of scattered solar power plants in Poland, mainly from the perspective of their communication networks, and how the recent development of the Polish 4G networks has a very positive impact for the performance of the whole monitoring system (production control and video-surveillance), with a special emphasis on video-analytics, due to its higher bandwidth demand. All the information will be shown from the point of view of the solar photovoltaics developer I+D Energías, and therefore it constitutes a real user’s experience.

This work is concerned with the existence and uniqueness of boundary value problems defined on semi-infinite intervals. These kinds of problems seldom admit exactly known solutions and, therefore, the theoretical information on their well-posedness is essential before attempting to derive an approximate solution by analytical or numerical means. Our utmost contribution in this context is the definition of a numerical test for investigating the existence and uniqueness of solutions of boundary problems defined on semi-infinite intervals. The main result is given by a theorem relating the existence and uniqueness question to the number of real zeros of a function implicitly defined within the formulation of the iterative transformation method. As a consequence, we can investigate the existence and uniqueness of solutions by studying the behaviour of that function. Within such a context the numerical test is illustrated by two examples where we find meaningful numerical results.

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.

Acknowledging the diverse perceptions about science-religion relationships among learners who come from various religious environments may increase learners’ willingness to learn about evolution. This study is based on a zoology course designed for in-service teachers, which aimed to provide basic scientific knowledge about evolution using the Religious Cultural Competence in Evolution Education framework. The study explores whether learners who were resistant to evolution modify their attitudes and willingness to learn about it, and whether they develop respect toward learners who hold contradicting views. Using qualitative methods, the findings indicate that using the Religious Cultural Competence in Evolution Education framework increased some formerly "resistant" learners’ willingness to learn about evolution and include it in their own teaching, albeit in varying degrees and with various reservations. The learners appreciated the freedom to express their challenges concerning evolution learning or teaching and became more willing to respect opposing perspectives, even though not all the religious learners accepted evolution as an explanation for the development of organisms. This study has international implications for bridging the gap between science and religion, thus reducing resistance to learning and teaching about evolution.

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

Aims: To report on the clinico-pathological features of a series of 12 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Methods and methods: All mucoepidermoid carcinomas diagnosed in the period 1990-2012 were retrieved, the original histological preparations were reviewed to confirm the diagnosis, and from selected cases, showing exclusive intra-cystic neoplastic component, additional sections were cut at 3 subsequent 200m intervals and stained with Hematoxylin-Eosin, PAS and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Also, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of 5 years. The neosplasm were located in the hard palate (9 cases), the soft palate (2), the cheeck (2) and the retromolar trigone (1). In all instances histological examination was revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue and no solid areas or infiltrating tumour clusters were detected. Conservative surgical resection was performed in all cases and no recurrences or nodal metastases were observed during the follow up period. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumours. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic fashion and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues or metastasize.

We study the center of energy (CE) before and after the separation of superposed wave from a moving medium (MM). It is assumed that two out-of-phase mechanical transverse waves propagating from the opposite directions on a medium moving at non-relativistic speeds are superposed and the superposed portion (SP) is separated from the MM at that moment. We consider the CE of the SP before and after the separation from the MM. The location of CE (LCE) of the SP seems to be at the center of it at the moment of superposition. The SP rotates due to the separation from the MM since the velocity of each portion symmetric with respect to the center of the SP is equal in magnitude and opposite in direction. The magnitudes of velocities of the symmetric portions become different as soon as the SP begins to rotate with the separation from the MM. Then the energies of their symmetric portions are not the same, so the LCE of the SP is not at the center of it. As a result, the LCE of it looks different before and after the separation from the MM. We must find a solution to keep the LCE of the SP constant. We propose that two out-of-phase mechanical transverse waves (MTWs) propagating from the opposite directions on a MM originally have hidden difference in relativistic energy and it suddenly appears within the range observable in Newtonian mechanics when the SP starts rotating. This means that the point of view of hidden difference in relativistic energy is necessary to keep the LCE constant.

Low-temperature processed ITO thin films offer the potential of overcoming the doping limit by suppressing the equilibrium of compensating oxygen interstitial defects. To elucidate this potential, electrical properties of Sn-doped In₂O₃ (ITO) thin films are studied in dependence on film thickness. In-operando conductivity and Hall effect measurements during annealing of room temperature deposited films with different film thickness in different environments allow to discriminate between the effects of crystallization, grain growth, donor activation and oxygen diffusion on carrier concentrations and mobilities. At 200 °C, a control of carrier concentration by oxygen incorporation or extraction is only possible for very thin films. The electrical properties of thicker films deposited at room temperature are mostly affected by grain size. The remaining diffusivity of compensating oxygen defects at 200 °C is sufficient to screen the high Fermi level induced by deposition of Al₂O₃ using atomic layer deposition (ALD), which disables the use of defect modulation doping at this temperature. The results indicate that achieving higher carrier concentrations requires a control of the oxygen pressure during deposition in combination with seed layers to enhance crystallinity or the use of near room temperature ALD.

The alignment of nanostructures in materials such as lyotropic liquid crystals (LLCs) templated materials has the potential to signicantly improve their performances. However, accurately characterising and quantifying the alignement of such fine structures remains very challenging. In situ small angle X-ray scattering (SAXS) and molecular dynamics were employed for the first time to understand the hexagonal LLC alignment process with magnetic nanoparticles under a magnetic field. The enhanced alignment has been illustrated from the distribution of azimuthal intensity in the samples exposed to magnetic field. Molecular dynamics simulations reveal the relationship between the imposed force of the magenetic nanoparticles under magnetic field and the force transferred to the LLC cylinders which leads to the LLC alignment. The combinational study with experimental measurement and computational simulation will enable the development and control of nanostructures in novel materials for various applications.

This article makes a general analysis of the supply chain of photovoltaic systems in Colombia, taking as a starting point a conceptual base and the current situation of the country in this sector. This article especially will contemplate the non-interconnected areas (ZNI) to the electricity grid in the national, due to its complexity in the logistics issues. Likewise, the work performs a graphical representation of the stages and processes of the supply chain using a powerful-modeled tool such as the Petri Nets (PNs). Finally, it identifies some of the flaws in the operation and the joint of all the links of the logistic part and from there it is based the importance of the strategy of orientation to the supply chain (SCO) as a possible alternative to improve and to enhance the logistic processes of this type of systems.

Since their discovery in 1993, numerous microRNAs (miRNAs) have been identified in humans and other eukaryotic organisms, and their role as key regulators of gene expression is still being elucidated. It is now known that miRNAs not only play a central role in the processes that ensure normal development and physiology, but they are often dysregulated in various diseases. In this review, we present an overview of the role of miRNAs in normal renal development and physiology, in maladaptive renal repair after injury, and in the pathogenesis of renal parenchymal diseases. In addition, we describe methods used for their detection and their potential as therapeutic targets. Continued research on renal miRNAs will undoubtedly improve our understanding of diseases affecting the kidneys and may also lead to new therapeutic agents.

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Different polyurethanes (PUs) were synthesized with polycarbonate polyols of molecular weights 500, 1000 and 2000 Da. Their self-healing abilities at 20 °C were tested and their structural, thermal, and mechanical properties were analyzed. The PUs made with polycarbonates of molecular weights 500 (YC500) and 1000 Da (YC1000) exhibited self-healing at 20 °C and the self-healing time of YC1000 was the shortest. The high mobility of the short polymeric chains, the absence of crystallinity and the low degree of micro-phase separation favored self-healing at 20 °C in YC500. However, the presence of tack and the existence of allophanate species and urethane-carbonate and urea-carbonate hydrogen bonds disfavored self-healing. Consequently, the self-healing time at 20 °C of YC500 was longer than expected. On the other hand, YC1000 exhibited an “equilibrium” between the urethane-carbonate and urea-carbonate hydrogen bonds and carbonate-carbonate interactions among the soft segments, so a particular structural order was produced which was associated to its fastest self-healing at 20 °C. The PU made with the polycarbonate of molecular weight 2000 Da did not exhibit self-healing at 20 °C because its significant micro-phase separation and the presence of semi-crystalline soft domains.

Global attention to climate change has surged since the advent of the Paris Agreement, intensifying the importance of measuring and managing carbon productivity indicators on a national level. Nevertheless, concerns persist regarding the reliability of such measurements because of inherent discrepancies in implementing and operating national-level carbon productivity indicators, coupled with their inherent uncertainty. This study proposes a multiple regression model to address these issues aimed at refining national-level carbon productivity indicators metrics, accounting for factors such as the gross domestic product and total greenhouse gas emissions by sectors. The objective was to offer insights into enhancing and effectively utilizing current indicators, enabling a more nuanced interpretation of the variation in the carbon productivity indicators across diverse industrial landscapes. This study showed that adjustments of the carbon productivity metrics reflect disparities in emissions across industrial structures, with countries characterized by high emissions from non-service industries showing improving trends. In addition, this paper proposes an auxiliary indicator estimating method for carbon productivity, emphasizing its utility in interpreting productivity indicators within the context of varying industrial compositions across OECD countries. This study underscores the inadequacies of the current national productivity estimating method, pinpointing areas requiring refinement. Specifically, the method for estimating the auxiliary indicator for carbon productivity guarantees enhanced rationality when integrated with current methodologies. Moreover, by elucidating the nuances of industrial structures, this study advocates for more sophisticated approaches to interpreting and managing the productivity indicators tailored to each unique economic landscape of each country. Nevertheless, the limitations stemming from data availability underscore the need for further research, particularly in refining the national-level carbon resource productivity indicators analyses and exploring the thematic productivity variations in greater depth. By addressing these gaps, future studies will contribute to a more comprehensive understanding of national-level carbon resource productivity indicators dynamics and reveal targeted strategies for sustainable development.

Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.

Air pollution has recently gained much attention from the general population. Despite pollution control being an issue in both urban and rural regions, most of the available research has concentrated on urban districts. Hence, investigations into how urban-rural transition affects PM2.5 are warranted within the framework of urban-rural integration. Using the Yellow River Basin as a case study, this study employed the entropy method and Analytic Hierarchy Process (AHP) to uncover the extent of urban-rural transformation. It then used the spatial autocorrelation method to investigate the spatiotemporal features of PM2.5 and the spatial econometric model to investigate the mechanisms that influence the relationship between urban-rural transformation and PM2.5. The results are as follows: (1) Over time, there was a discernible upward tendency in the change in urban-rural areas. The development has progressed from asymmetrical north-east and south-west elevations to a more balanced pattern of north-east, middle-east, and west-west elevations. (2) The PM2.5 concentration increased steadily, then fluctuated, and finally decreased. Notably, the general pattern has not changed much, and it is high in the east and low in the west. (3) Different subsystems of the urban-rural transformation have different impacts on air pollution at different stages. The influence of industrial transformation (IT) on PM2.5 showed an inverted “N-shaped” curve of negative-positive-negative changes, and the industrial structure played a leading role in the spatiotemporal evolution of PM2.5. Currently, an inverted "U-shaped" curve forms the left side of the impact of population transition (PT) on PM2.5. Land development (LT) has a "U-shaped" curve for its effect on PM2.5. This research provides a new perspective on the topic of PM2.5 and its connection to urban-rural integration, which is crucial to understanding the dynamics of this shift. To achieve its goal of high-quality development, it supports regional initiatives to reduce PM2.5 emissions in the Yellow River Basin. Moreover, it can provide a reference for decision-makers in the world’s densely populated areas that suffer from serious air pollution.

When separation to the parameters of interest appears below resolution limit of the estimator, the ambiguity arises whether two parameter estimates relate to one source emitted twice or two close sources emitted once. In the paper, novel Bayes technique aimed to identify one/two sources below resolution limit by the pair of Gaussian estimates of a source(s) planar location as parameter is developed. Prior probabilities of the hypotheses on one/two sources are available from the analysis of physical characteristics of the emissions, assuming that they can be equally probable. The identifier recalculates a posteriori these probabilities subject to a distance between sources. It is applied to distinguish two location estimates obtained in the planar time difference of arrival mobile communication network. The work of the identifier is studied in the domain of closely spaced network users where covariance matrices of estimates are sufficiently approximated by the constant. The application gives an example of how the identifier revises the prior probabilities and can change thereby the initial preference of a hypothesis with a distance between users in some cases.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on October 27, 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1 respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerises. The differences between ephemeris DE440 and DE430 are smaller than those between DE440 and DE421.

This paper presents a new method for parameterizing the Lorentz group based on coupled parameters. From the Euler–Hamilton equations, an additional angular rapidity and perpendicular rapidity are obtained, and the Hamiltonian and Lagrangian of a relativistic particle are expanded into rapidity spectra. A so-called passage to the limit is introduced that makes it possible to decompose physical quantities into spectra in terms of elementary functions when explicit decomposition is difficult. New rapidity-dependent Lorentz-invariant coordinates are obtained, and the descriptions of particle motion using the old and new Lorentz-invariant forms as applied to plane waves are compared. Based on a classical model of particle motion in the field of a plane monochromatic electromagnetic wave and in that of a plane laser pulse, the rapidity-dependent spectral decompositions into elementary functions are presented, and the Euler–Hamilton equations are derived as rapidity functions in 3+1 dimensions.

The purpose of this paper was to examine the differences in using agricultural entrepreneurship support and in how it relates to characteristics such as the agrarian structure, socioeconomic de-velopment level and land use across the Polish territory. The analyses were carried out at district (poviat) level which is an intermediate administrative unit. The study found that the decisions on co-financing the measures dedicated to non-agricultural economic activity heavily depend on the agrarian structure. The highest levels of activity were witnessed in districts where the agrar-ian structure is particularly fragmented.

In this work, we report on the first attempt using size-controlled ZnO nanoparticles (NPs) to analyze role of thioacetamide (TAA) in forming ZnS nanostructures from ZnO. The size-controlled B(blue)_, G(green)_, Y(yellow)_ZnO QDs, and NC (nanocrystalline)_ZnO NPs were synthesized by sol-gel process as well as hydrothermal method, respectively and then reacted with an ethanolic TAA solution as sulfur source. After reacting with TAA, the formation of ZnS QDs was observed over time. The chemical reactions were identified using X-ray diffraction (XRD), Transmission Electron Microscope (TEM), UV-vis spectroscopy, and Photoluminescence (PL). All results indicate that ZnS formation is due to direct crystal growth and/or chemical conversion of ZnO to ZnS. Our results enable a broader understanding of the synthetic mechanisms involved in the use of TAA as a sulfur source in forming ZnS nanostructures from ZnO.

There are close dynamic relationships among the livelihood, well-being, and ecological environment of farm households. It is of great significance to scientifically clarify the impact of the grain for green policy on the livelihoods and well-being of farm households in mountainous areas. Based on data from a survey of 392 farm households in Zhangbei County, a system of indicators for farm household livelihood assets and farm household well-being was constructed, drawing on a sustainable livelihood framework (SLF). The livelihood assets and well-being levels of different types of farm households were measured, and a multiple linear regression model was used to analyze the impact of the grain for green policy implementation on the well-being levels of farm households. The three main results are as follows: (1) The level of natural assets among the total average livelihood assets of farm households in Zhangbei County is the highest at 0.374, while the level of physical assets is the lowest at 0.018. The level of livelihood assets of returned farmland households (0.948) is lower than that of nonreturned farmland households (1.117). (2) The level of well-being of all farm households in Zhangbei County is 0.517, with the level of wealth contributing the most to the well-being of farm households at 40.20% and the quality of the ecological environment contributing the least at 11.99%. The level of well-being of returned farmland households (0.518) was slightly higher than that of nonreturned farmland households (0.514). (3) The degree of influence of each influence factor on the level of well-being of farm households varies significantly. Household size was the strongest driver, at 0.366, while educational attainment of household members, household labor capacity, annual household expenditure, livelihood diversity, number of large production tools, and total value of livestock were also important drivers of household well-being, and area of arable land is negatively associated with household well-being. There are also differences in the factors influencing the level of well-being of different types of farming households.

This research suggests a multi-stakeholder framework to increase the use of fintech in Africa, which would help the continent boost its financial inclusion and reach its Sustainable Development Goals (SDGs). The study evaluates previous research and frameworks that have been created to aid in the adoption of fintech by several stakeholders in developing nations, some of which have been tested in African nations with limited success. To begin with, the study suggests the use of the World Bank’s Maximising Finance for Development (MFD) approach through the prioritization of national ownership, creation of an enabling environment for private sector investment, partnering with multilateral development banks and other stakeholders, fostering innovation and digital literacy, and focusing on cost-effective, non-government guaranteed financing. In the same vein, in line with the G20’s High-Level Principles for Digital Financial Inclusion, the adoption of financial technologies and digital financial services in Africa can be promoted through the creation of a country-specific strategy. Each government can create a regulatory environment that encourages innovation and competition, improve its digital infrastructure, increase its digital literacy and awareness, and collaborate with private sector stakeholders to expand financial inclusion. Furthermore, The Better Than Cash Alliance’s strategy to increase fintech adoption can also be implemented through partnership with businesses, international organizations, and other nations. By joining the Alliance, countries can enact rules and regulations that facilitate fintech adoption, promote awareness and education, and design and execute national digital payment infrastructure with the help of fintech companies. Finally, the mSTAR initiative suggests collaborating with USAID, in order to provide support to underrepresented populations, incorporate digital financial services, increase public-private collaboration, and educate and train policymakers, practitioners, and technologists. By implementing these strategies, African nations can accelerate the adoption of fintech solutions and increase financial inclusion.

We prove a version of Ekeland Variational Principle (EkVP) in a weighted graph $G$ and its equivalence to Caristi fixed point theorem and to Takahashi minimization principle. The usual completeness and topological notions are replaced with some weaker versions expressed in terms of the graph $G$. The main tool used in the proof is the OSC property for sequences in a graph. Converse results, meaning the completeness of graphs for which one of these principles holds is also considered.

Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

The extended finite element method (XFEM) is now widely used in crack simulations and the direction of propagation of the XFEM crack in SS-304 has been quite interesting. This paper discusses the direction,θ(+ve in anti-clockwise direction), of the XFEM crack (under mode-I) propagation based on the von Mises stress-field around the crack-tip for static loading under the light water reactors (LWRs) conditions. The Mises core region from the crack-tip is chosen for β=〖90〗^o, the angle between the load and the initial crack. Experimental data for LWRs’environment is obtained and the simulations have been carried out applying three different static loads and results for the direction of the crack are calculated by measuring the stress-field around the crack-tip. It has been found that the direction of the XFEM varies inversely as the stress-field around the crack tip is increased. The computational results have been compared with the numerical results based on the minimum strain energy density criterion[S-criterion].

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled in the ocular surface. To evaluate the safety, tolerability, and biologic activity of TALF, an animal study and a phase I clinical assay was performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biologic activity of the formulation. No inflammation, lens opacity, swelling or intraocular pressure rising were recorded after the instillation of TALF in any of the animal or clinical study. Mainly, mild and transient adverse events such as dry eye (30%) and burning (30%) were reported. TALF improves significantly visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biologic activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroids IVTs and its associated hazards.

Based on the observation and reanalysis data, the relationship between Madden-Julian Oscillation (MJO) over the Maritime Continent (MC) and the tropical Pacific-Indian Ocean temperature anomaly mode is analyzed. The results showed that the MJO over the MC region (100°-140°E, 10°S-5°N) (referred to as MC-MJO) possesses prominent interannual and interdecadal variations and seasonally "phase-locked" features. MC-MJO is strongest in the boreal winter and weakest in the boreal summer. Winter MC-MJO kinetic energy variation has significant relationships with the El Niño-Southern Oscillation (ENSO) in winter and the Indian Ocean Dipole (IOD) in autumn, but it correlates better with the tropical Pacific-Indian Ocean associated mode (PIOAM). The correlation coefficient between the winter MC-MJO kinetic energy index and the autumn PIOAM index is as high as -0.43. This means that when the positive (negative) autumn PIOAM anomaly strengthens, the MJO kinetic energy over the winter MC region weakens (strengthens). However, the correlation between the MC-MJO convection and PIOAM in winter is significantly weaker. The propagation of MJO over the Maritime Continent differs significantly in the contrast phases of PIOAM. During the positive phase of the PIOAM, the eastward propagation of the winter MJO kinetic energy always fails to move across the MC region and cannot enter the western Pacific. However, during the negative phase of the PIOAM, the anomalies of MJO kinetic energy over the MC is not significantly. MJO can propagate farther eastward and enter the western Pacific. One thing must be pointed out that there is a significant difference between the propagation of MJO convection over the MC region in winter and that of the MJO kinetic energy. That said, the MJO convection is more likely to extend to the western Pacific in the positive phases of PIOAM than in the negative phases

Objectives: Studies evaluating machine learning (ML) algorithms on cross-lingual RadLex® mappings for developing context-sensitive radiological reporting tools are lacking. Therefore, we investigated whether ML-based approaches can be utilized to assist radiologists in providing key imaging biomarkers – such as The Alberta stroke programme early CT score (APECTS). Material and Methods: A stratified random sample (age, gender, year) of CT reports (n=206) with suspected ischemic stroke was generated out of 3997 reports signed off between 2015-2019. Three independent, blinded readers assessed these reports and manually annotated clinico-radiologically relevant key features. The primary outcome was whether ASPECTS should have been provided (yes/no: 154/52). For all reports, both the findings and impressions underwent cross-lingual (German to English) RadLex®-mappings using natural language processing. Well-established ML-algorithms including classification trees, random forests, elastic net, support vector machines (SVMs) and boosted trees were evaluated in a 5 x 5-fold nested cross-validation framework. Further, a linear classifier (fastText) was directly fitted on the German reports. Ensemble learning was used to provide robust importance rankings of these ML-algorithms. Performance was evaluated using derivates of the confusion matrix and metrics of calibration including AUC, brier score and log loss as well as visually by calibration plots. Results: On this imbalanced classification task SVMs showed the highest accuracies both on human-extracted- (87%) and fully automated RadLex® features (findings: 82.5%; impressions: 85.4%). FastText without pre-trained language model showed the highest accuracy (89.3%) and AUC (92%) on the impressions. Ensemble learner revealed that boosted trees, fastText and SVMs are the most important ML-classifiers. Boosted trees fitted on the findings showed the best overall calibration curve. Conclusions: Contextual ML-based assistance suggesting ASPECTS while reporting neuroradiological emergencies is feasible, even if ML-models are restricted to be developed on limited and highly imbalanced data sets.

In this paper, we firstly consider extended degenerate central factorial numbers of the second kind and provide some properties of them. We then introduce unified degenerate central Bell polynomials and numbers and investigate many relations and formulas including summation formula, explicit formula and derivative property. Moreover, we derive several correlations for the fully degenerate central Bell polynomials associated with the degenerate Bernstein polynomials and the degenerate Bernoulli, Euler and Genocchi numbers.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on Z_p of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

This systematic review critically examines the adoption and integration of Human Resource Information Systems (HRIS) and Artificial Intelligence (AI) in small and medium-sized enterprises (SMEs), with a focus on enhancing workforce productivity and strategic decision-making. Using the PRISMA framework, 100 research articles from reputable sources such as Google Scholar, Scopus, and Web of Science were analyzed. The analysis reveals that HRIS adoption can improve employee productivity by 29%, decision-making by 20%, and operational efficiency by 26%, highlighting its transformative impact on SMEs. The review identifies major challenges, including high implementation costs, limited IT resources, and integration difficulties with AI and machine learning technologies. Despite these barriers, integrating AI into HRIS presents significant opportunities for SMEs, fostering innovation in talent management, compliance automation, and data-driven decision-making, thus creating a competitive edge in rapidly evolving markets. Actionable insights for practitioners emphasize the need for cost-effective, scalable HRIS solutions tailored to the unique operational needs of SMEs, while researchers are urged to further explore AI-driven HRIS advancements to address current gaps in workforce engagement and performance management. This review offers a comprehensive roadmap for future HRIS innovations and underscores the strategic importance of digital transformation in human resources for sustained SME competitiveness.

The rapid development of specific-purpose Large Language Models (LLMs), such as Med-PaLM, MEDITRON-70B, and Med-Gemini, has significantly impacted healthcare, offering unprecedented capabilities in clinical decision support, diagnostics, and personalized health monitoring. This paper reviews the advancements in medicine-specific LLMs, the integration of Retrieval-Augmented Generation (RAG) and prompt engineering, and their applications in improving diagnostic accuracy and educational utility. Despite the potential, these technologies present challenges, including bias, hallucinations, and the need for robust safety protocols. The paper also discusses the regulatory and ethical considerations necessary for integrating these models into mainstream healthcare. By examining current studies and developments, this paper aims to provide a comprehensive overview of the state of LLMs in medicine and highlight the future directions for research and application. The study concludes that while LLMs hold immense potential, their safe and effective integration into clinical practice requires rigorous testing, ongoing evaluation, and continuous collaboration among stakeholders.

It is often said in human society that it all starts from the mind, and this is true. The answer to the question “Why is it that pets require much fewer years to fully develop than humans?” could be headed to the Theory of Relativity and the perceived time according to the levels of instinct and rationality. It is perhaps no wonder that the French language translates the word “mind” as “l’esprit”, which also means “spirit” in the English language. Given that the Theory of Relativity applies to all physical matter, the theory applies to chemistry, biology and psychology as well. The level of instinct is proportional with the perceived speed of time and implicitly, to the speed of time itself for the whole organism, given that the nervous system coordinates all bodily functions. A pet may experience a few years as humans experience over a decade, making their perceived lifetime to be approximately equal to the human’s. The same applies to the perception of space and its components. This aspect would emphasise upon the fact that all life on Earth shows the same degree of value with regards to uniqueness. Nevertheless, the values represented by the hierarchy of competences among living organisms at the same time differs based on species. Honour of uniqueness and hierarchy of competences represent two scientific concepts that never overcross. As a result, there is no evidence to suggest that scientific facts as such constitute a form of contradiction to philosophical and religious ideas, given that religion refers to animals as companions of humans. With regards to the clock of the living organism; there are three kinds of clocks in a living organism: the emotional clock, the cognitive clock and the molecular clock. These three categories actually constitute the temporal layers of our dimension, so they are in a relationship of interdependence. When one has a feeling that time is slower or quicker, they are not fully experiencing that change in the time speed, but only partially. And one can profoundly experience the change of perceived time speed when they experience profound feelings, which sweep them away from reality. Complete, deep mental focus can bring about this profound change in perception, which will make the individual feel as if they are in a different form of reality. When one is more instinctive, the person in cause perceives time as slower and sees more opportunities within the same frame of time and space. When one experiences the “Fight or flight” mode, the person in the cause finds themselves to be in danger and has two options; to try to prevail over the danger or to flee it. Whilst experiencing such a mode, people are much more alert and therefore, time passes more slowly and the physical space dilates. When people are relaxed, however, time and space become smaller, and when they are in a deep state of resting, they become very small. And where there is a smaller dimension, there is a greater speed, just as the circulating air gains speed when it crosses narrow passages.

Humans have a unique cognitive ability known as relational abstraction, which allows us to identify logical rules and patterns beyond basic perceptual characteristics. This ability represents a key difference between how humans and other animals learn and interact with the world. With current large language models rivaling human intelligence in many regards, we investigated whether relational abstraction was an emergent chat completion capacity in various models. We find that despite their impressive language processing skills, all tested language models failed the relational match-to-sample (RMTS) test, a benchmark for assessing relational abstraction. These results challenge the assumption that advanced language skills inherently confer the capacity for complex relational reasoning. The paper highlights the need for a broader evaluation of AI cognitive abilities, emphasizing that language proficiency alone may not be indicative of certain higher-order cognitive processes thought to be supported by language.

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible pre-cancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the ap-plication of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced im-munocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-, IL-6, and neopterin). VGE exhibits a progressive reduction followed by an increase (p<0.0001) which parallels in-flammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p<0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg-1 creatinine (p<0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.ml-1 (p<0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p=0.005), respectively. The variation after each dive was held constant around 158.3 ± 6.9% (p = 0.021); 151.4 ± 5.7% (p <0.0001); 176.3 ± 11.9% (p<0.0001); and 160.1 ± 5.6% (p<0.001), respectively. When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei.

Human violence recognition is an area of great interest in the scientific community, given its broad spectrum of applications, especially in video surveillance systems, since detecting violence in real-time could prevent criminal acts and save lives. Despite the number of existing proposals and research, most focus on the precision of results, leaving aside efficiency and its practical implementation. Thus, this work proposes a model that is effective and efficient in recognizing human violence in real-time. The proposed model consists of three modules: a first module called Spatial Motion Extractor (SME), in charge of extracting regions of interest from a frame; a second module called Short Temporal Extractor (STC), whose function is to extract temporal characteristics of rapid movements, finally the Global Temporal Extractor (GET) module, responsible for identifying long-lasting temporal features and fine-tuning the model. The proposal was evaluated regarding efficiency, effectiveness, and ability to operate in real-time. The results obtained on Hockey, Movies, and RWF-2000 datasets demonstrated that this approach is highly efficient compared to other alternatives. A VioPeru dataset was created to validate real-time applicability with violent and non-violent videos captured by real video surveillance cameras in Peru. The effectiveness results in this dataset outperformed the best existing proposal. Therefore, our proposal has contributions in efficiency, effectiveness, and real-time.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

In modern security situations, tracking multiple human objects in real-time within challenging urban environments is a critical capability for enhancing situational awareness, minimizing response time, and increasing overall operational effectiveness. Tracking multiple entities enables informed decision-making, risk mitigation, and the safeguarding of civil-military operations to ensure safety and mission success. This paper presents a multi-modal electro-optical/infrared (EO/IR) and radio frequency (RF) fused sensing (MEIRFS) platform for real-time human object detection, recognition, classification, and tracking in challenging environments. By utilizing different sensors in a complementary manner, the robustness of the sensing system is enhanced, enabling reliable detection and recognition results across various situations. Specifically designed Radar tag and thermal tag can be used to discriminate friendly and non-friendly objects. The system incorporates deep learning-based image fusion and human object recognition and tracking (HORT) algorithms to ensure accurate situation assessment. After integrating into an all-terrain robot, multiple ground tests were conducted to verify the consistent HORT in various environments. The MEIRFS sensor system has been designed to meet the Size, Weight, Power, and Cost (SWaP-C) requirements for installation on autonomous ground and aerial vehicles.

The adipose-derived mesenchymal stem cells are becoming the tool of choice for many clinical applications and nowadays, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type for many diseases and pathological conditions. To reach the goal of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize the GMP processes and thus collection methods, transportation strategies, extraction protocols and characterization procedures without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability genetically determined and acquired during life. Here we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. Variability in the age of patients, gender and laboratory parameters like total cell number, cell viability, stem cell number and other stromal vascular fraction cell sub-populations have been compared to each other. Results show that, when the laboratory protocol is standardized, the variability in quantifiable cell parameters is widely statistically non-significant, meaning that we can make a further step toward standardized advanced cell therapy products.

Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormones (TH) transmembrane transporters relevant for the availability of TH in neural cells, crucial for their proper development and function. Mutations in MCT8 or OATP1C1 result in severe disorders with dramatic movement disability related to alterations in basal ganglia motor circuits. Mapping the expression of MCT8/OATP1C1 in those circuits is necessary to explain their involvement in motor control. We studied the distribution of both transporters in the neuronal subpopulations that configure the direct and indirect basal ganglia motor circuits using immunohistochemistry and double/multiple labeling immunofluorescence for TH transporters and neuronal biomarkers. We found their expression in the medium-sized spiny neurons of the striatum (the receptor neurons of the corticostriatal pathway), and in various types of its local microcircuitry interneurons, including the cholinergic. We also demonstrate the presence of both transporters in projection neurons of intrinsic and output nuclei of the basal ganglia, motor thalamus and nucleus basalis of Meynert, suggesting an important role of MCT8/OATP1C1 for modulating the motor system. Our findings suggest that a lack of function of these transporters in the basal ganglia circuits would significantly impact motor system modulation, leading to clinically severe movement impairment.

We live in the world that is completely entangled on energy and thus, Humankind can no longer do without it, power. With electricity being the main form of energy today, this has increased the complexity of our life today. In Uganda, electricity generation is mainly through hydropower which put the country in the bottleneck of over dependence on one source of energy. Yet, there are many energy systems out there that country can diversify its electricity generation. Therefore, the need to understand, the level of development and utilization of various energy systems has been the underlying question for this present study. Comprehensive literature survey was conducted from the electronic databases including ScienceDirect, Wiley, Sage, Scopus, Taylor & Francis, and Google Scholar. The publications in form of reports, conference papers, working papers, discussion papers, journal articles, book sections and textbooks were considered in this study. In total, 11 energy systems including human and animal energy, solid biomass (firewood), hydropower, wind, geothermal, solar, nuclear, peat, coal, petroleum, and non-solid biomass (methanol, hydrogen, ethanol, biodiesel, and biogas) are described. The current and the future development and utilization of these energy systems has been described. The challenges with their development and utilization were elaborated and the solution the challenges were presented. The hydropower with River Nile being the main river for large hydropower plant construction is the dominance energy system in Uganda. Nuclear energy will be the salvation for the country’s electric energy supply in the near future. Therefore, Uganda needs to bet big on nuclear energy.

The spillover of a virus from an animal reservoir to humans requires both molecular and ecological risk factors to align. While extensive research both before and after the emergence of SARS-CoV-2 in 2019 implicates horseshoe bats as the significant animal reservoir for the new human coronavirus, it remains unclear why it emerged at this time. One massive disruption to animal-human contacts in 2019 is linked to the on-going African swine fever virus (ASFV) pandemic. Pork is the major meat source in the Chinese diet. We hypothesize that the dramatic shortage of pork following large-scale culling and restrictions of pig movement (resulting in marked price increases) led to alternative sources of meat and unusual animal and meat movements nationwide, e.g., involving wildlife, and thus greatly increased opportunities for human-sarbecovirus contacts. Pork prices were particularly high in southern provinces (Guangdong, Guangxi, Fujian, Jiangxi, Hunan, and Hubei), where wildlife is farmed and more frequently consumed. Major wildlife farming provinces are spread from Northern to Southern China, which overlaps with horseshoe bat host ranges, potential hosts of the proximal SARS-CoV-2 ancestor, and wildlife sourcing provinces of Wuhan Huanan market and possibly other markets. Trading of SARS-CoV-2 susceptible wildlife in these markets, such as minks, raccoon dogs, foxes and palm civets in Wuhan markets, could have increased the risk of SARS-CoV-2 from an intermediary host. Moreover, large quantities of animals raised for fur could have entered the human food chain undetected and significantly increased risks of animal-human contact. Performing retrospective testing of stored susceptible animals and their meat sold before December 2019 may be helpful in the next stage of tracing the animal origin of SARS-CoV-2 as spillover events are more likely to have taken place in 2019 when China was experiencing the worst effects of the ASFV pandemic.

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap where human factor was seen as an important source of errors and disruptions. Today the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised the awareness about the central role humans have to play in manufacturing systems, to the design of which they must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different Human dimensions associated with CPS and IoT and focuses on their conceptual evolution of automatization to improve the sociability of such automated production systems and consequently puts again the human in the loop. Hereby, our aim is to take stock of current research trends, and to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. As results, different models of sociability as way to integrate human into the broad sense and/or the development of future automated production systems, were identified from the literature and analysed.

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

The cyclic regeneration of human endometrium is guaranteed by the proliferative capacity of Endometrial Mesenchymal Stromal Cells (E-MSCs). Due to this, the autologous infusion of E-MSCs has been proposed to support endometrial growth in a wide range of gynecological diseases. We aimed to compare two different endometrial sampling methods, the surgical curettage and the Vacuum Aspiration Biopsy Random Assay, and to validate a novel xeno-free method to culture human E-MSCs. Six E-MSCs cell lines were isolated after a mechanical tissue homogenization and cultured using human platelet lysate. E-MSCs were characterized for the colony formation capacity, proliferative potential and multilineage differentiation. The expression of mesenchymal and stemness markers was tested by FACS analysis and Real-Time PCR, respectively. Chromosomal alterations were evaluated by karyotype analysis, whereas tumorigenic capacity and invasiveness were tested by soft agar assay. Both endometrial sampling techniques allowed to efficiently isolate and expand E-MSCs using a xeno-free method preserving their mesenchymal and stemness phenotype, proliferative potential and multi-lineage differentiation ability during the culture. No chromosomal alterations and invasive/tumorigenic capacity were observed. Herein we report the first evidence of efficient E-MSCs isolation and culture in Good Manufacturing Practice compliance conditions, suggesting Vabra endometrial sampling as alternative to surgical curettage.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

A two-link model of exoskeleton with variable-length links for supporting the lower limbs of the human musculoskeletal system is proposed in the article. The researched model differs from the existing ones by the variable-length links, and by the angle calculation method. While in the existing models, the angles are calculated from the regular direction – from vertical, or from horizontal, - in the proposed research they are calculated between the links. As for practical exoskeleton implementation, the proposed method of angle calculation is appropriate to the actual working conditions of the electrical motors with the reduction gears installed in the hinges, which change the angles between the links. The mathematical model in the form of the system of Lagrange differential equations of the second kind is obtained. The obtained mathematical model is examined for existence and uniqueness of the Cauchy solution. The kinematic trajectory of the link motion has been synthesized. The controlling actions required for its implementation have been found.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

Social distancing is a recommended solution by the World Health Organisation (WHO) to minimise the spread of COVID-19 in public places. The majority of governments and national health authorities have set the 2-meter physical distancing as a mandatory safety measure in shopping centres, schools and other covered areas. In this research, we develop a Deep Neural Network-based Model for automated people detection, tracking, and inter-people distances estimation in the crowd, using common CCTV security cameras. The proposed DNN model along with an inverse perspective mapping technique leads to a very accurate people detection and social distancing monitoring in challenging conditions, including people occlusion, partial visibility, and lighting variations. We also provide an online infection risk assessment scheme by statistical analysis of the Spatio-temporal data from the moving trajectories and the rate of social distancing violations. We identify high-risk zones with the highest possibility of virus spread and infection. This may help authorities to redesign the layout of a public place or to take precaution actions to mitigate high-risk zones. The efficiency of the proposed methodology is evaluated on the Oxford Town Centre dataset, with superior performance in terms of accuracy and speed compared to three state-of-the-art methods.

Victor Vasarely’s (1906-1997) important legacy to the study of human perception is brought to the forefront and discussed. A large part of his impressive work conveys the appearance of striking three-dimensional shapes and structures in a large-scale pictorial plane. Current perception science explains such effects by invoking brain mechanisms for the processing of monocular (2D) depth cues. Here in this study, we illustrate and explain the local effects of 2D color and contrast cues on the perceptual organization in terms of figure-ground assignments, i.e. which local surfaces are likely to be seen as “nearer” or “bigger” in the image plane. Paired configurations are embedded in a larger, structurally ambivalent pictorial context inspired by some of Vasarely’s creations. The figure-ground effects these configurations produce reveal a significant correlation between perceptual solutions for “nearer” and “bigger” when no other monocular depth cues are given in the image. In consistency with previous findings on similar, albeit simpler visual displays, a specific color may compete with luminance contrast in resolving the planar ambiguity of a complex pattern context. Vasarely intuitively understood, and successfully exploited, this kind of subtle context effect in his art, well before empirical investigations had set out to study and explain their genesis in terms of information processing by the visual brain.

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells that has a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template in molecular imprinting. The magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs) were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis and superconducting quantum interference device (SQUID) analysis. Natural killer-92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and the quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found significantly enhance the activity of natural killer cells toward HepG2 cells by increasing expression of NK-kB, caspase 8 and especially caspase 3.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

Abstract Introduction: Visual perceptual skills are essential for independent participation in self-care tasks, educational, work and leisure time activities. The effect of HIV on the visual perceptual skills is not well understood among children in low resource settings like Zimbabwe. Methods: A cross sectional comparative study was done with 30 children living with HIV and 30 children living without HIV residing in Harare urban area. The TVPS-3 was used to assess their visual perceptual skills. SPSS version 22, STATISTICA 13 and Microsoft 2016 were used for data analysis. Results: Both groups of children had mean percentile ranks below 50 on their TVPS-3 scores. Children without HIV generally performed better than those with HIV but the difference was not statistically significant in most cases. Through univariate analysis, only performance on Spatial Relations significantly differed between the two groups. Both groups had lowest scores in Basic visual perceptual skills. Age and school grade were the independent predictors of the children’s performances in the study. Conclusion: There is need for Occupational therapy services in public primary schools and in the pediatric Opportunistic Infections clinics in hospitals to be part of the health team which caters for children with visual perceptual challenges.

To cope with a projected global population increase from 7.2 bn to 9.6 bn by 2050, many more cities must be built. Although there are great benefits to modern urban living, there also great costs, such as the seemingly unstoppable rise in Type 2 diabetes, obesity, coronary issues and various cancers. The new towns should be designed to contain or constrain the epidemic of those ‘Western Lifestyle Diseases’ that currently plagues today’s cities. But how might this be achieved? It is suggested here that a greater understanding of human evolution combined with the potency of the ‘Palaeolithic genome’ holds the key to our future urban wellbeing. Consequently, a new paradigm is suggested that underpins positive forward thinking on townplanning and city lifestyles to create healthier urban environments. This builds directly on the ‘Evolutionary Determinants of Health’ programme initiated at University College London (UCL). A four-stage model is proposed that integrates and develops both evolutionary-concordant personal and institutional health behaviours with appropriately reconfigured town-planning and building regulations. When integrated, these strands could deliver a healthier urban culture within greened, active townscapes by proactively constraining or eliminating some of the key underlying causes of the so-called ‘Western Lifestyle Diseases’.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options