In this paper, we aim to present real implementation cases where non-visible elements of environmental impact assessments (EIA), wind flow, are visualized using a 3D digital twin technology. The conventional EIA process serves as a crucial tool in the evaluation of potential environmental impacts prior to the initiation of development projects. This evaluation helps to establish a legal and institutional framework that seeks to minimize the adverse effects on the environment. However, traditional EIA methods present challenges, particularly for non-experts, in comprehending the results of assessments involving non-visible environmental factors such as noise, air quality, and wind flow. These elements are often represented in static images or numerical tables, limiting accurate understanding and engagement. Our proposed method, termed Digital Twin based EIA, addresses these limitations by leveraging digital twin technology. This advanced methodology allows for the visualization of non-visible environmental elements in a spatio-temporal dimension, providing a more interactive and comprehensive user interface/experience for both citizens and stakeholders. In this context, we present a unique case study that focuses on visualizing wind flow using this technology. This paper serves as an example of how digital twin platforms can enhance traditional EIA processes, offering a more immersive and informative experience. The evolution of EIA into the digital realm signifies an important step forward in fostering public understanding and engagement in environmental protection efforts.

With the development of organizational biology and forced from the EU Cosmetic Regulation (EU/1223/2009) with the complete ban of animal testing for cosmetic purposes, 3D skin models have been widely developed due to their similar physiological structure and metabolic function to native human tissue. 3D skin models for in vitro cosmetic evaluation are still promising alternative methods for evaluating phototoxicity, corrosivity and irritation. These models have been used for early screening and later validation of toxicity and efficacy evaluation by many well-known cosmetic companies. 3D skin models have become an important tool in cosmetic evaluation research. This article reviews the development of 3D skin models and their application in cosmetic evaluation. An outlook on the current application and future technological development directions in the cosmetic field is also presented.

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modelling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues are becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging on chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.

New in vitro approaches for the assessment of their toxicity are crucial for creating better risk assessments given the growing use of nanoparticles (NPs) in the production of consumer goods. Humans will be exposed to nanoparticles through the inhalation route from contaminated aerosol. A promising method for evaluating the genotoxicity of NPs in vitro uses human airway epithelial cells. This study aimed to determine whether there were differences in morphology change of human bronchial/tracheal epithelial (HBTEC) cells responded to NPs in 2D and 3D spheroid models and to evaluate genotoxicity in 2D and 3D cultures after 24 hr exposure to TiO2-, Ag- and ZnO-NPs using the comet assay. Our 2D and 3D HBTEC cultures with TiO2-NPs did not show any statistically significant genotoxicity compared to controls for concentration points tested in vitro. HBTEC cells grown as 2D indicated that exposure to ZnO-NPs at low concentrations (10-50 ug/mL) for 24 hr did not cause any genotoxic effect but, at high concentrations, genotoxicity was observed. In contrast, treatment of 2D HBTEC with AgO-NPs led to an elevated in percentage of tail DNA damage from 50 ug/mL to 100 ug/mL, which was concentra-tion-dependent. Using 3D spheroid assays revealed a lower %tail length in ZnO- and AgO-NPs, thus exhibiting in vitro genotoxicity of NPs in this cell model. Spheroids (3D) rather than mono-layer cultures (2D) are believed to more precisely represent in vivo-like cell behavior when evaluating genotoxicity. Together, our findings demonstrate the genotoxic effects of NPs and point to the critical role that cell culture models play in the evaluation of toxicological risk.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Osteoarthritis (OA) is a joint disease involving cartilage degeneration. This study aimed to compare properties of chondrocytes from less-affected (LA-Cartilage) and severely-affected (SA-Cartilage) of human OA articular cartilage. Based on Dougados classification, OA cartilage was classified into two groups; less-affected (Grade 0–1) and severely-affected (Grade 2–3). Chondrocytes from each group were cultured until passage (P) 4. Growth, migration, stem cell properties and chondrogenic properties under normal and inflammatory conditions, and the formation of in vitro 3D cartilage tissues were compared between groups. The growth and migratory properties of LA-chondrocytes and SA-chondrocytes were similar, except that the migration rate of SA-chondrocytes was significantly higher at P0 compared to LA-chondrocytes. Both LA-chondrocytes and SA-chondrocytes expressed mesenchymal stem cell markers and tri-lineage differentiation, but the expression of stem cell markers decreased significantly with increasing passage number. Exposure to inflammatory conditions induced distinct morphological changes and significant increases in expression of SOX9 at P4 and MMP3 at P1 for LA-chondrocytes. LA-chondrocytes and SA-chondrocytes able to develop into in vitro 3D constructs, but SA-chondrocytes exhibited superior cartilage-like properties. Chondrocytes from both less- and severely-affected regions are suitable to be used in clinical applications, however, chondrocytes from severely-affected regions could be a more favorable cell source.

3D city models are being extensively used in applications such as evacuation scenarios and energy consumption estimation. The main standard for 3D city models is the CityGML data model which can be encoded through the CityJSON data format. CityGML and CityJSON use polygonal modelling in order to represent geometries. True topological data structures have proven to be more computationally efficient for geometric analysis compared to polygonal modelling. In a previous study, we have introduced a method to topologically reconstruct CityGML models while maintaining the semantic information of the dataset, based solely on the combinatorial map (C-Map) data structure. As a result of the limitations of C-Map's semantic representation mechanism, the resulting datasets could suffer either from semantic information loss or the redundant repetition of them. In this article, we propose a solution for a more efficient representation of both geometry, topology and semantics by incorporating the C-Map data structure in the CityGML data model and implementing a CityJSON extension to encode the C-Map data. In addition, we provide an algorithm for the topological reconstruction of CityJSON datasets to append them according to this extension. Finally, we apply our methodology to three open datasets in order to validate our approach when applied to real-world data. Our results show that the proposed CityJSON extension can represent all geometric information of a city model in a lossless way, providing additional topological information for the objects of the model.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

Endoscopy has made a significant and noteworthy contribution to the field of medical science and technology. Nevertheless, its potential remains constrained due to the limited availability of rigid or flexible endoscopes. This paper introduces a novel hydraulic actuator based on electrorheological fluid (ERF) as a pivotal advancement in bridging the existing gap within the realm of endoscopy. Following a comprehensive introduction that briefly outlines the electrorheological effect, the subsequent section is dedicated to the elucidation of the actuator’s development process. Challenges arise, particularly in terms of miniaturization and the realization of a hydraulically sealed system with integrated valve electrodes. An internal electrorheological valve system consisting of four valves that are controlled using a pulse-width modulated high voltage was suitable for position control of the antagonistic hydraulic actuators. High-precision stereolithography (SLA) printing has proven practical for manufacturing the actuator components. For functional testing, a test bench was set up in which the actuator follows a setpoint through a PI control loop. The control deviation ranged from 0.6 to 1 degree, with a response time between 6 and 8 seconds. The experiments have demonstrated that, through the use of ERF and integrated valve electrodes, a miniaturized functional actuator can be constructed.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x104 – 2x107 CFU per ml and has a sensitivity of S = 1.655x105 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10-9 grams (g) which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

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

The individual and combined effects of extracellular products (ECP) from Arthrobotrys oligospora (Ao) and A. musiformis (Am) growth in liquid media against Haemonchus contortus L3 (HcL3) were assessed. The following methodological steps were established: isolation, morphological (MI) and molecular identification (Mol-I), assessment of nematocidal activity (NA) of fungal liq-uid culture filtrates (LCF) produced in two liquid media alone and in combination and finally, the myco-compound profile identification (MCP). The MI of both isolates suggested that the fungi corresponded to the species Ao and Am. This result was confirmed by PCR analysis followed by sequencing, alignment and obtaining coverage and similarity with respect to isolates reported in the NCBI database. Likewise, the highest Hc mortalities were 91.4% with individual LCF of Am and 86.2% with those of Ao at the highest concentration (100 mg/mL) in Czapek-Dox Broth. The combination of both LCF resulted in a similarly high larval mortality with no statistical differ-ences in relation to individual activity (P>0.05). The MCP showed the presence of alkaloids in both fungi. Coumarins, triterpenes and saponins were found only in Ao. Both fungi produced ECP with a high NA that could be identified and assessed in future studies as potential natural an-thelmintic compounds.

Water footprint has been widely used to illustrate the consumption of water in many situations; for instance, in products, processes or regions of interest. In this work, we analyzed – using a sensitivity analysis approach – the effect of some variables in the calculation of the water footprint in the viticulture in Brazilian Serra Gaúcha (the major producing region of Brazilian Wine).The classical Penman-Monteith model for evapotransporation was considered, with uncertainties in some parameters (dead mulch covering fraction in the vineyard, maximum temperatures for some months, altitudes and latitudes of the site). The sensitivity analysis was conducted using the SAFE toolbox under Octave framework. The results indicated that the the portion of the water footprint corresponding to the evapotranspiration is more sensitive to the values of mulch covering fraction and the altitude of the site in comparison with the latitude and the maximum temperatures.

Understanding the dynamics of Organic Carbon mineralization is fundamental in forecasting biosphere to atmosphere Net Carbon Ecosystem Exchange (NEE). With this perspective, we developed 3D-CMCC-PSM, a new version of the hybrid Process Based Model 3D‐CMCC FEM where also heterotrophic respiration (R_h) is explicitly simulated. The aim was to quantify NEE as a forward problem, by subtracting Ecosystem Respiration (R_eco) to Gross Primary Productivity (GPP). To do so, we developed a simplification of the Soil Carbon dynamics routine proposed in DNDC [1]. The method calculates decomposition as a function of soil moisture, temperature, state of the organic compartments, and relative abundance of microbial pools. Given the pulse dynamics of soil respiration, we introduced modifications in some of the principal constitutive relations involved in phenology and littering sub-routines. We quantified the model structure related uncertainty in NEE, by running our training simulations over 1000 random parameter-sets extracted from parameters distributions expected from literature. 3D-CMCC-PSM predictability was tested on independent time series for 6 Fluxnet sites. The model resulted in daily and monthly estimations highly consistent with the observed time series. It showed lower predictability in Mediterranean ecosystems, suggesting that it may need further improvements in addressing evapotranspiration and water dynamics.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

We review some recent developments about strongly interacting relativistic Fermi theories in three spacetime dimensions. These models realize the asymptotic safety scenario and are used to describe the low-energy properties of Dirac materials in condensed matter physics. We begin with a general discussion of the symmetries of multi-flavor Fermi systems in arbitrary dimensions. Then we review known results about the critical flavor number $N_\mathrm{crit}$ of Thirring models in three dimensions. Only models with flavor number below $N_\mathrm{crit}$ show a phase transition from a symmetry-broken strong-coupling phase to a symmetric weak-coupling phase. Recent simulations with chiral fermions show that $N_\mathrm{crit}$ is smaller than previously extracted with various non-perturbative methods. Our simulations with chiral SLAC fermions reveal that for four-component flavors $N_\mathrm{crit}=0.80(4)$. This means that all reducible Thirring models with $\Nr=1,2,3,\dots$ show no phase transition with order parameter. Instead we discover footprints of phase transitions without order parameter. These new transitions are probably smooth and could be used to relate the lattice Thirring models to Thirring models in the continuum. For a single irreducible flavor, we provide previously unpublished values for the critical couplings and critical exponents.

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

Additive manufacturing (AM) processes, including stereolithography (SL), can fabricate complex ceramic parts layer by layer using computer-aided design (CAD) models. A ceramic slurry with high solid loading is usually used in SL to fabricate the desired shape, which is further sintered to produce the final part. The traditional SL system utilizes a tank filled with printable material, known as a vat, which for ceramic slurry contributes several limitations and operational difficulties, and further renders it non-recyclable mainly due to its high viscosity and the fragility of the green state. In this study, we utilized a continuous film supply (CFS) printer integrated with a tape casting system using in-house-designed ceramic slurry to print standard prototype specimens. Various printing parameters, including viscosity, layer thickness control, and slurry recycling efficiency, were studied. In addition, post-processing optimizations of the prototype, characterizations, and the microhardness of sintered samples were studied to determine their properties and compare them with traditional methods. The effectiveness of slurry reusability was demonstrated by printing with original and recycled slurry to produce consistent densification of final parts. Post-processing was optimized to achieve a relative sinter density of 99.02% and microhardness of 12.59 GPa. This method provides new opportunities to realize dense complex ceramic features with final properties comparable to those produced by subtractive machining and traditional SL. Furthermore, slurry recycling helps to reduce the overall cost and material consumption.

Members of the genus Armillaria are widespread forest pathogens against which effective protection has not yet been developed. Due to their longevity and the creation of large-scale cloning of Armillaria individuals, the use of mycoviruses as biocontrol agents (BCAs) against these pathogens could be an effective alternative. This work describes the screening of double-stranded RNA banding patterns as a first approach for potential virus discovery and the use of stranded total RNA-seq for viral detection and characterization in Armillaria spp. collected in the Czech Republic. A total of five single-stranded RNA viruses were detected in Armillaria ostoyae and A. cepistipes, including the first virus of the family Tymoviridae found infecting a member the genus Armillaria and four viruses belonging to the recently described virus group "ambiviruses" with circular ambisense genome organization. Both hammerhead (HHRz) and hairpin (HpRz) ribozymes were detected in all the ambiviricot sequences. Armillaria viruses were compared by phylogenetic analysis and confirmed their specific host by direct RT-PCR, which showed the occurrence of interspecies transmission.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity. In a previous study, we identified a subset of murine effector CTLs expressing the hepatocyte growth factor (HGF) receptor c-Met (c-Met+ CTLs) that are endowed with enhanced cytolytic capacity. HGF directly inhibited the cytolytic function of c-Met+ CTLs, both in 2D in vitro assays and in vivo, leading to reduced T cell responses against metastatic melanoma. To further investigate the role of c-Met+ CTLs in a three-dimensional (3D) setting, we studied their function within B16 melanoma spheroids and examined the impact of cell-cell contact on the modulation of inhibitory checkpoint molecules expression such as KLRG1, PD-1 and CTLA-4. Additionally, we evaluated the cytolytic capacity of human CTLs clones expressing c-Met (c-Met+) and compared it to c-Met− CTLs clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTLs clones exhibited increased cytolytic activity compared to c-Met− CTLs clones, and this enhanced function was negatively regulated by the presence of HGF. Taken together, our findings highlight the potential of targeting the HGF/c-Met pathway to modulate CTL-mediated anti-tumor immunity. This research holds promises for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer.

This work presents datasets that can be used for getting a good understanding of an essential geoscience content knowledge that describe earth’s coordinate systems. This include coordinate system used for spherical/spheroidal earth with latitudes and longitudes and their subsequent transformations to 2d maps on a variety of media (paper as well as digital) using the process of map projections. The datasets include PDF documents that are embedded with 3d models, animations and mathematical equations. The dataset has separate PDF documents for geographic (for spherical earth) and projected (2d) coordinate systems. Additionally, the data set include individual 3d models that can be used in various digital systems (including apps) and the animations in mp4 format that can be watched on most of the modern digital devices.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Computer extended Descriptive Geometry (CeDG) is a new approach to solve and build computer models of three dimensional (3D) geometrical systems through descriptive geometry procedures that have demonstrated reliability and accuracy. CeDG may calculate a parametric algebraic exact form for the spatial curves generated in the intersection of two surfaces, as well as of the flattened pattern of any developable surface involved in those encounters. This study presents first the theoretical foundations and methodology to calculate those parametric algebraic curves. Secondly, a compound hopper is defined and modelled through CeDG (implemented in GeoGebra) and CAD (Solid Edge 2023) approaches to evaluate the advantages of CeDG against CAD. The results demonstrate the robustness and accuracy of the CeDG technique for surfaces intersection and flattening and the advantages of CeDG against Solid Edge 2023 in solving the hopper case study.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research. In vivo and in vitro disease models have been instrumental in casting light on complex polygenic, multifactorial, and heterogeneous disease mechanisms. In the most recent years, advanced preclinical models have revealed the intriguing interaction of sex/gender and aging with the pathogenesis and clinical manifestations of psychiatric and neurological diseases. However, despite these advancements, there is still a great deal of work to be done to fully comprehend the underlying mechanisms of these diseases and to develop treatments that can significantly improve the lives of those who suffer from them. The current challenge in the field of neurological and psychiatric diseases is to develop disease-modifying, effective treatments for these complex and long-lasting debilitating conditions with a high burden of disease.The first edition of the research topic ‘Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models’ reinforces translational research playing a critical role in bridging the gap between basic research and clinical applications. Also, it provides a platform for researchers to share their findings and advancements in translational research in this field. This new collection gathers 25 papers offering insights into the latest advancements in translational research and potential new avenues for treatments. These papers cover various topics, including the development of new preclinical models, the use of in vitro and in vivo methods, and the application of qualitative and quantitative research methods.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Morphological dissimilarity and its evolution over time are one of the most unexpected variations found when comparing cell cultures in 2D and 3D. Monolayer cells appear to flatten in the lower part of the plate, adhering to and spreading in the horizontal plane while not extending vertically. Consequently, cells developed in two dimensions have a forced apex-basal polarity. Co-cultivation and crosstalking between multiple cell types, which control development and formation in the in vivo counterpart, are possible in 3D cultures. With or without a scaffold matrix, 3D model culture may exhibit more in vivo-like morphology and physiology. 3D cultures mimic relevant physiological cellular processes, transforming them into one-of-a-kind drug screening platforms. The structures and dynamics of regulatory networks, which are increasingly studied with live-imaging microscopy, must be considered to help and guarantee the functional maintenance of a 3D structure. However, commercially available technologies that can be used for current laboratory needs are minimal, despite the need to make it easier to acquire cellular kinetics with high spatial and temporal resolution, in order to improve visual efficiency and, as a result, experimentation performance. The CELLviewer is a newly developed multi-technology instrument that integrates and synchronizes the work of various scientific disciplines. The aim of this study is to test the device using two different models: a single Jurkat cell and an MCF-7 spheroid. The two models are loaded into the microfluidic cartridge for each experiment after they have been grown and captured in time-lapse for a total of 4 hours. The samples used are tracked under the operation of the optics after adaptive autofocus, while slipping inside the cartridge chamber, and the 3D rotation was successfully obtained experimentally. The MitoGreen dye, a fluorescence marker selectively permeable to live cells, was then used to determine cell viability. To measure the model diameter, construct fluorescence intensity graphs along a straight line passing through the cell, and visualize the spatial fluorescence intensity distribution in 3D, ImageJ software was used.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

Digital twins are gaining in popularity for simulating complex natural and urban environments. In this context, accurate segmentation of objects within 3D urban environments is of crucial importance. The aim of this project is to develop a methodology for extracting buildings from textured 3D meshes. To this end, PicassoNet-II, a semantic segmentation architecture is employed. The methodology also incorporates Markov field-based contextual analysis to assess post-segmentation features. In addition, building instantiation is performed using cluster analysis algorithms. Training this model to fit various datasets requires a large amount of annotated data, both from Quebec City, Canada, and from simulated data. Experimental results show that the use of simulated data improves segmentation accuracy, and the DBScan algorithm proves effective in extracting isolated buildings. This project paves the way for improved applications in 3D urban modeling, offering opportunities in fields ranging from urban planning to resource management. The positive results with simulated data reinforce the impact of this research on improving digital models of our ever-changing urban environments.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

The importance of conflict analysis and safety considerations during work zone intervals at signalized intersections cannot be overstated, as these periods pose unique challenges and safety risks for both motorists and pedestrians. Work zones introduce temporary changes to traffic patterns, lane configurations, and signal timings, which can disrupt the flow of traffic and increase the likelihood of conflicts between vehicles and pedestrians. By conducting comprehensive conflict analysis, it is possible to identify potential conflict points, such as merging areas, pedestrian crossings, and lane transitions, and implement targeted safety measures to mitigate risks. Additionally, considering safety considerations during work zone intervals is paramount to safeguarding the well-being of road users and minimizing the occurrence of conflicts or collisions. Measures such as enhanced signage, temporary traffic control devices, and increased enforcement efforts can help promote compliance with traffic regulations and ensure the safe passage of vehicles and pedestrians through work zones. This study investigates the dynamics of traffic behavior and safety implications within work zones at signalized intersections, aiming to address key challenges and enhance intersection management strategies. Through comprehensive analysis, varying frequencies of Vehicle-to-Vehicle (V2V) conflicts were observed across different movement directions, with significant occurrences identified in specific phases of the traffic signal cycle. Specifically, 69 V2V conflicts in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8 were recorded. Furthermore, the examination of Vehicle-to-Pedestrian (V2P) conflicts underscored the importance of prioritizing pedestrian safety, with notable occurrences observed in phases associated with pedestrian crossing movements. Meanwhile, despite the closure of left-turn movements, instances of red light running persisted, with 69 red light running events in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8.To mitigate these safety concerns during work zone intervals, proactive measures are essential. Strategies include improving communication through clear signage and advanced warning systems, enhancing enforcement efforts with red light cameras and increased police presence, and investing in infrastructure improvements such as temporary pedestrian facilities. Integration of real-time data from sensors, particularly LiDAR technology, offers significant advantages in detecting conflicts and red light runners during work zone intervals. LiDAR's precise, real-time data on vehicle and pedestrian movements, combined with its 360-degree coverage and high spatial resolution, facilitates accurate detection and tracking of potential conflict scenarios, contributing to enhanced intersection safety and traffic management efficiency. This study endeavored to conduct a traffic safety analysis during work zone intervals at a signalized intersection in Baltimore City, known for its high rate of traffic crashes, utilizing LiDAR sensor technology.

Lake sediment records are of great importance for understanding the evolution of watershed environments. Various studies have been carried out to constrain the depositional ages of lake sediments and examine their physical, chemical, and biological characteristics, aiming to construct historical vegetation, environment and climate patterns in Chinese lake watersheds. In this study, we obtained relevant literature on lake sediment records by searching the key word 'age-depth' from the databases – Web of Science and China National Knowledge Infrastructure (CNKI, the largest Chinese academic database). We analyzed the literature based on its type (published in a Chinese/English journal or as a Master’s/PhD thesis), period of publication, journal (if published in a journal), key authors, study area, dating scale, and main aims. The results suggest that the lakes in the plateau regions are the most popular research topic typically covering 100–200 years (short-term) and 500–30,000 years (long-term). The literature focuses on a wide range of topics, from past environmental evolution in the watershed to lake ecology, and provides a solid foundation for better understanding regional climate change and the preservation of lake environments and ecosystems. In the future, resulting data from environmental reconstruction with lake sediments will be needed to integrate with emerging information processing technologies (e.g., artificial intelligence and meta-analysis), to disentangle the complex interplay between Earth surface processes and global climate change; furthermore, strengthening interdisciplinary collaboration will deepen our comprehension of man-land relationship and promote the sustainable management of lake ecosystems in the context of global climate change.

Skin inflammation associated with chronic diseases has the direct action of keratinocytes in its immunopathogenesis, leading to a series of immune responses. However, there are still no highly targeted treatments, and the development of more specific therapies is highly desirable. In the present work, nanocapsules containing quinizarin (QZ/NC) were developed, evaluating their act in a model of the keratinocytes inflammatory process in vitro with the action of Photodynamic Therapy, analyzing the permeation in a 3D skin model. Physicochemical, stability, cytotoxicity and permeation analyses of the nanomaterials were carried out. The nanocapsules showed desirable physicochemical characteristics and were stable during the analysis period, without spectroscopic modifications. The cell viability test carried out showed no cytotoxicity at the lowest QZ/NC concentrations. The permeation and cellular uptake studies showed the permeation of QZ/NC in 3D skin models and the intracellular incorporation and internalization of the drug, enhancing its action in the drug delivery technique. Promising results were presented using the model developed to induce the inflammatory process in vitro and applying the synthesized nanomaterial in conjunction with PDT, where a decrease in the levels of cytokines analyzed was observed, representing a possible new therapeutic approach for inflammatory skin diseases.

In this paper, we proposed the fusion of two projection based face recognition algorithms: local binary Patterns in DCT domain and singular value decomposition (SVD) characterized by its simplicity and efficiently. Standard databases ORL are used to test the experimental results which prove that proposed system achieves more accurate face recognition as compared to individual method.

With the ongoing amendment of the EU legislation on the treatment of urban wastewater, stricter requirements for the removal of pollutants are expected, which calls for the need for innovative wastewater treatment technologies. Biological systems are still the first choice. The survey of typical bioreactors applied in wastewater treatment is presented. Wastewater treatment objective, bio-chemical environment and microbial growth are selected as a main criterion for classification of these bioreactors. Hydraulic and kinetic aspects are considered, advantages and drawbacks of these bioreactors regarding the selection of appropriate type of the reactor as well as regarding operation of reactors are mentioned. The aim of this paper is to provide operators and designers with a brief overview of selected traditional and advanced processes, reactors, and technologies for nutrient removal from municipal wastewater. Another goal is to discuss the possibilities and limitations to comply with more strict effluent standards. From the evaluation of the published papers, it follows that the currently applied traditional methods of nutrients removal have the potential to convey also with the expected stricter limits.

A method of direction-of-arrival (DoA) estimation for FMCW radars is presented. In addition to MUSIC and ESPRIT, which are well-known high-resolution DoA estimation algorithms, deep learning has recently emerged as a very promising alternative. It is proposed in this paper to use a 3D convolutional neural network (CNN) for DoA estimation. The 3D-CNN extracts from the radar data cube spectrum features of the region of interest (RoI) centered on the potential positions of the targets, thereby capturing the spectrum phase shift information, which corresponds to DoA, along the antenna axis. Finally, the results of simulations and field experiments are provided to demonstrate the superior performance, as well as the limitations, of the proposed 3D-CNN.

Despite the recognized influence of maximum or acceleration strength on combat techniques and countermovement jump (CMJ) performance, the relationship between body segment weights and combat techniques remains unexplored. This study aimed to examine the impact of body segment weights, including striking arm weight (SAW), kicking leg weight (KLW), and trunk weight (TW), on the dynamics of direct punches (DP), palm strikes (PS), elbow strikes (ES), front kicks (FK), and CMJ performance. Sixteen male military cadets (22.3±1.8 years, 181.4±7.0 cm, 83.0±8.1 kg) performed combat techniques, with performance measured by using a force plate and body segment weights assessed by Dual-energy X-ray absorptiometry. Spearman's correlation analysis was applied. Results indicated a strong correlation between KLW and FK impulse (r = 0.64, p ≤ 0.01) and CMJ impact force (r = 0.80, p ≤ 0.01). SAW showed moderate correlations with DP impulse (r = 0.53, p ≤ 0.05) and ES impulse (r = 0.54, p ≤ 0.05). Additionally, FK peak and impact forces were strongly correlated with CMJ jump height (r = 0.74, p ≤ 0.01; r = 0.77, p ≤ 0.01), and FK peak force moderately correlated with CMJ peak velocity (r = 0.63, p ≤ 0.05). These findings suggest targeted arm strength training could enhance striking abilities, while improvements in leg acceleration strength may directly boost kicking performance and vertical jump capabilities, which are crucial in combat scenarios.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Livestock farming plays a crucial role in agriculture and is important in meeting people's needs for a better life in the new era. However, due to China's "double carbon" target, the development of animal husbandry has been affected by the level of carbon emissions. To study the spatial dis-tribution and dynamic evolution of livestock carbon emissions in Shandong Province, we used panel data from 16 prefecture-level cities in Shandong Province from 2001 to 2022 to determine the spatial differentiation of livestock carbon emissions in Shandong Province and their dynamic evolution by combining spatial and non-parametric estimation methods based on livestock carbon emissions and livestock emission intensity measured by city. The results of the study show that the distribution of carbon emissions from animal husbandry in Shandong Province is in a "dis-persed-aggregated" pattern, and the intensity of carbon emissions shows a gradual downward trend, with a ladder-like distribution characterized by high in the west and low in the east. Through the analysis of the dynamic evolution of nuclear density, we observe that the regional differences of animal husbandry carbon emissions in Shandong Province are expanding, showing the characteristics of polarization. The difference of carbon emissions in the peninsula is gradually narrowing, and the phenomenon of polarization is weakening. The carbon emissions of animal husbandry in the central and western regions of Shandong are polarized.

In Germany, the phloem sucking planthopper Pentastiridius leporinus (Hemiptera: Cixiidae) currently represents the epidemiological driver for the spread of the syndrome “Basses Richesses” in sugar beet, which results in a reduced sugar content and an economic loss for the farmers. This disease is associated with the γ-proteobacterium ‘Candidatus Arsenophonus phytopathogenicus’ and the Stolbur phytoplasma ‘Candidatus Phytoplasma solani’. Recently, P. leporinus was found in potato fields in Germany associated with Stolbur-like symptoms in this crop. In this study, we confirmed that the vector completes its lifecycle on sugar beet as well as on potato when reared under controlled conditions. Transmission experiments with adults of this vector combined with molecular analyses showed for the first time that both pathogens are transmitted by this vector to potato. For an accurate assessment of the Ca. P. solani and Ca. A. phytopathogenicus titers in the vector and host plants, gBlocks derived from the hsp20- and 16S rRNA gene were employed, respectively. For Ca. P. solani the limit of detection was determined in potato and sugar beet material. The results of this study will further research on the epidemiology of the syndrome “Basses Richesses” and “Stolbur” diseases and the response of host plants and vector insects to both pathogens.

Fingerprints are essential for human identification and are valuable tools in criminal investigations. The pursuit of new materials for digital printing is expanding, with increasing interest in natural compounds such as bixin, sourced from annatto seeds. Despite its traditional use as a natural dye with medicinal properties, the potential of bixin in papilloscopy remains largely untapped. In this study, we meticulously extracted bixin from annatto seeds and meticulously developed composites incorporating zinc carbonate (bixin/ZnCO3) and kaolinite (bixin/kaolinite). UV-visible spectroscopy was used for characterization, and the extracted bixin showed absorption peaks at 429, 453, and 481 nm, which were very similar to standard peaks at 429, 457, and 487 nm. The two samples also had the same retention times (7.07 min) according to further liquid chromatography analysis. Sweat pores were easier to detect thanks to the effectiveness of the bixin/ZnCO3 and bixin/kaolinite composites in creating high contrast sebaceous and natural latent fingerprints. These results highlight the composites’ potential as novel and fascinating instruments for papilloscopy applications, which might also improve forensic investigations.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Latin America and the Caribbean offer the most favorable natural and social conditions for the emergence of cattle ranching that regenerate and maintains the ecosystem services on which life on Earth depends, that is energy efficient and that contributes to meeting fundamental human food needs. Unlike other major global producers, cattle farming in Latin America and the Caribbean is fundamentally based on pasture. Therein lies both its strength (due to the regenerative potential of well-managed pastures) and its vulnerability (due to the pervasive link between deforestation and pasture formation, especially in the Amazon, where 40% of the Brazilian herd is concentrated). The diversification of pastures (today marked by impressive monotony, with brachiaria accounting for 85% of the species in Brazil), the introduction of legumes and tree plantations within them, and the proper management of herds, open the way to the possibility of drastically reducing the area currently occupied by the activity (especially in the Amazon) while maintaining the supply of its products. Agricultural research has disseminated forms of moderate intensification of cattle ranching, which represent a low opportunity cost of animal feed and, at the same time, regeneration of ecosystem services that have so far been destroyed by the prevailing methods of farming.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of Calcium Deficient HydroxyApatite (CDHA) intended as future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds and its post-processing at three temperatures (1200, 1300, 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of the cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300°C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300°C and 1400°C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.

Identifying influential actors within social networks is pivotal for optimizing information flow and mitigating the spread of both rumors and diseases. Several methods have emerged to pinpoint these influential entities in networks that are represented as graphs. In these graphs, nodes corre-spond to individuals and edges indicate their connections. This study focuses on centrality measures, prized for their straightforwardness and effectiveness. We categorize structural central-ity into two: local, considering a node's immediate vicinity, and global, accounting for overarching path structures. Some techniques blend both centralities to highlight nodes influential at both mi-cro and macro levels. Our paper presents a novel centrality measure, accentuating node degree and incorporating the network's broader features, especially paths of different lengths. Through Spearman and Pearson's correlations tested on seven standard datasets, our method proves its merit against traditional centrality measures. Additionally, we employ the SIR model, portraying disease spread, to further validate our approach. The ultimate influential node is gauged by its capacity to infect the most nodes during the SIR model's progression. Our results indicate a nota-ble correlative efficacy across various real-world networks relative to other centrality metrics.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

The conformity assessment of products or a measured value with the given standards is carried out based on the global risk of producers and consumers calculation. A product may conform to specifications but be falsely rejected as non-conforming. This is about the producer's risk. If a product doesn't meet the requirements but is falsely accepted as conforming, that poses a risk to the consumer. The conventional approach to risk assessment, which yields only a single numerical value for the global risk of producers and consumers, is naturally extended, and utilized for assessing risk in measurement models with linear regression. The outcomes of the two-dimensional extension, along a moderate scale, are the parabolas with an opening upwards. Risk surfaces were obtained through three-dimensional extension over the area limited by the moderate scale and guard band axes. Four models with different ranges of tolerance intervals were used to test this innovative method of risk assessment in linear regression. The corresponding standard measurement uncertainties are determined by applying a simplified measurement model with the use of comprehensive data on the measurement performance and by determining measurement uncertainty derived from consideration of the functional relationship obtained by linear regression analysis. Models that utilize information from linear regression analysis to determine measurement uncertainty are biased towards risks at the edges of the moderate scale. Testing the model's performances with metrics related to the confusion matrix, such as the F1 score, further substantiated this assertion. The diagnostic odds ratio has been proven to be extremely effective in identifying the curve along the guard band axis, along which the global risks of producers and consumers are at their lowest.

In this paper, a new approach to retrieve semantic images based on shape and geometric features of image in conjunction with multi-class support vector machine is proposed. Zernike moment as shape feature is to verify the invariance of objects for silhouette image. In addition, a set of geometrical features is to explore the objects shape using two features of rectangularity and circularity. Then the extracted features are normalized and employed for multi-class support vector machine either for learning or retrieving processes. The retrieving process relies on three main tasks which namely Query Engine, Matching Module and Ontology Manger, respectively. Query Engine is to build the input text or image query using SPARQL language. The matching module extracts the shape and geometric features of image’s objects and employ them to Ontology Manger which in turn inserts them in ontology knowledge base. Benchmark mammals have been conducted to empirically conclude the outcome of proposed approach. Our experiment on text and image retrieval yields efficient results to problematic phenomena than previously reported.

3D-mapping-aided (3DMA) global navigation satellite system (GNSS) positioning that improves positioning performance in dense urban areas has been under development in the recent years, but it still faces many challenges. This paper details a new algorithm that explores the potential of using building boundary for positioning. Rather than applying complex simulations to analyze and correct signal reflections by buildings, the approach utilizes a convolutional neural network to differentiate between the sky and building in a sky-pointing fisheye image. A new skymask matching algorithm is then proposed to match the segmented fisheye images with skymasks generated from a 3D building model. Each matched skymask holds a latitude and longitude coordinate to determine the precise location of the fisheye image. The results are then compared with the conventional GNSS and advanced 3DMA GNSS positioning methods. The aims of the proposed algorithm are to increase positioning and heading accuracy in a rich urban environment.

The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

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

The Internet of Things (IoT) is a concept based on the integration of various devices and methods of communication to exchange information in order to contribute to the improvement of everyday life, business and environment. This paper focuses on the establishment of a modern Internet of Things platform to ensure secure collection, processing and storage of data, under unexpected events. This platform establishes reliable connectivity which enhance system uptime; the key to success when implementing an IoT strategy. For this purpose, we proposed a hybrid approach combining different connectivity technologies to ensure the availability and smooth operation of the system and the prevention of data loss in unforeseen cases.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P<0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P<0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

Manual visual inspections typically conducted after an earthquake are high-risk, subjective, and time-consuming. Delays from inspections often exacerbate the social and economic impact of the disaster on affected communities. Rapid and autonomous inspection using images acquired from unmanned aerial vehicles offer the potential to reduce such delays. Indeed, a vast amount of re-search has been conducted toward developing automated vision-based methods to assess the health of infrastructure at the component and structure level. Most proposed methods typically rely on images of the damaged structure, but seldom consider how the images were acquired. To achieve autonomous inspections, methods must be evaluated in a comprehensive end-to-end manner, incorporating both data acquisition and data processing. In this paper, we leverage recent advances in computer generated imagery (CGI) to construct a 3D synthetic environment for simulation of post-earthquake inspections that allows for comprehensive evaluation and valida-tion of autonomous inspection strategies. A critical issue is how to simulate and subsequently render the damage in the structure after an earthquake. To this end, a high-fidelity nonlinear finite element model is incorporated in the synthetic environment to provide a representation of earthquake-induced damage; this finite element model, combined with photo-realistic rendering of the damage, is termed herein a physics-based graphics models (PBGM). The 3D synthetic en-vironment with PBGMs provide a comprehensive end-to-end approach for development and validation of autonomous post-earthquake strategies using UAVs, including: (i) simulation of path planning of virtual UAVs and image capture under different environmental conditions; (ii) au-tomatic labeling of captured images, potentially providing an infinite amount of data for training deep neural networks; (iii) availability of the ground truth damage state from the results of the finite-element simulation; and (iv) direct comparison of different approaches to autonomous as-sessments. Moreover, the synthetic data generated has the potential to be used to augment field datasets. To demonstrate the efficacy of PBGMs, models of reinforced concrete moment-frame buildings with masonry infill walls are examined. The 3D synthetic environment employing PBGMs is shown to provide an effective testbed for development and validation of autonomous vision-based post-earthquake inspections that can serve as an important building block for ad-vancing autonomous data to decision frameworks.

This article proposes the use of a multi-scale and multi-sensor approach to collect and modelling 3D data concerning wide and complex areas in order to obtain a variety of metric information in the same 3D archive, based on a single coordinate system. The employment of these 3D georeferenced products is multifaceted and the fusion or integration among different sensors data, scales and resolutions is promising and could be useful for the generation of a model that could be defined as hybrid. The correct geometry, accuracy, radiometry and weight of the data models are hereby evaluated comparing integrated processes and results from Terrestrial Laser Scanner (TLS), Mobile Mapping System (MMS), Unmanned Aerial Vehicle (UAV), terrestrial photogrammetry, using Total Station (TS) and Global Navigation Satellite System (GNSS) as topographic survey. The entire analysis underlines the potentiality of the integration and fusion of different solutions and is a crucial part of the “Torino 1911” project whose main purpose is mapping and virtually reconstructing the 1911 Great Exhibition settled in the Valentino Park in Turin (Italy).

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

There is a need to find methods to intensify the anaerobic digestion process. One possibility is the use of pre-treatment techniques. Many laboratory tests confirm their effectiveness, but in most cases, there is no verification work carried out on industrial plants. The aim of the research carried out under laboratory conditions and on a large scale was to determine the technological and energy efficiency of the use of hydrodynamic cavitation in the pre-treatment of a waste mixture from dairy farms. It has been shown that hydrodynamic cavitation significantly increases the concentration of organic compounds in the dissolved phase. In the most effective variants, the increase in the content of these indicators was over 90% for both COD and TOC. The degree of solubilisation achieved was 49±2.6% for COD and almost 52±4.4% for TOC. Under laboratory conditions, the highest effects of anaerobic digestion were achieved after 10 minutes of pre-treatment. The amount of biogas was on average 367±18 mL/gCOD and the amount of methane 233±13 mL/gCOD. Further large-scale optimisation trials showed that after 8 minutes of hydrodynamic cavitation, the biogas yield was 327±8 L/kgCOD with a CH4 content of 62.9±1.9%. With this variant, the net energy yield was 66.4±2.6 kWh/day, a value that was 13.9% higher than the original variant with 10 minutes of disintegration and 3.1% higher than the variant without pre-treatment.

Background: Fiber-reinforced composites (FRCs) have been proposed as an alternative to traditional metal alloys for the realization of frameworks in full-arch implant supported prostheses. The aim of the present in vitro study was to evaluate the deflection under load of seven prostheses endowed with frameworks made of different materials, including different types of fiber reinforced composites (FRCs). Methods: A master cast with four implant analogues in correspondence of the two lateral incisors and the two first molars was used to create full-arch fixed prostheses with the same shape and different materials. Prostheses were made in different materials (framework+veneering material): gold alloy+resin (Au+R), titanium+resin (Ti+R), FRC with multi-directional carbon fibers+resin (ICFRC+R), FRC with unidirectional carbon fibers+composite (UCFRC+C), FRC with glass fibers+resin (GFRC+R), FRC with glass fibers+composite (GFRC+C), resin (R, full-acrylic prosthesis). Flexural tests were conducted using Zwick/Roell Z 0.5 machine and the deflection of the lower surface of the prosthesis was measured in order to obtain load/deflection graphs. Results: Greater rigidity and less deflection were recorded for UCFRC+C, GFRC+C, followed by Ti+R, and Au+R. The greatest deformations were observed for resin alone, ICFRC+R and GFRC+R. The results were slightly different in the incisal region probably due to the greater amount of veneering material in this area. Conclusions: When used to realize full-arch frameworks, Au and Ti allow a predictable mechanical behavior with gradual deformations with increasing load. UCFRC also demonstrated good outcomes and less deflection than ICFRCs when loaded. The GFRC full-arch framework may be a valid alternative, however showed greater deflections. Further studies are needed in order to evaluated how different prosthesis design and material thickness might affect the outcomes.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Atopic dermatitis (AD) is a chronic inflammatory disorder presenting a dysregulated immune response and derangement of the epidermal barrier lipids. The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signal axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D-epidermal equivalents. We used tofacitinib, a low-molecular-mass JAK inhibitor, to screen for the JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4, and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase, and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitate and caused a depletion of triglycerides. This depletion was associated with altered PC profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very long chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by halted homeostasis of FA metabolism.

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix, and in mice fed with EAA rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing autophagy and apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable anti-proliferative properties.

We generalize the point information gain (PIG) and derived quantities, i.e., point information gain entropy (PIE) and point information gain entropy density (PIED), for the case of the Rényi entropy and simulate the behavior of PIG for typical distributions. We also use these methods for the analysis of multidimensional datasets. We demonstrate the main properties of PIE/PIED spectra for the real data on the example of several images, and discuss further possible utilizations in other fields of data processing.

Depressions containing partially molten rocks were investigated in Quaternary pebbly sedi-ments in Alpine foreland in Bavaria, Germany. Ruins of limekilns from 18-19th centuries are abundant around Seeshaupt. They are usually associated with earthworks for fuel feeding and protection from wind. Depressions contain partially molten stones from furnace walls, with lime and burnt loam remnants. On the surface of pebbles (typically gneisses), green glass formed with chemical composition possibly affected by moderately volatile components of wood biomass, mainly K and Cu. Thermoplastic deformation of pebbles is limited and the sur-face melt deformation points to slow flow. At Emmerting, on the other hand, two walled circu-lar depressions which lack additional earthworks have been identified as possible impact cra-ters. Thermally affected pebbles show much more intense deformation. Colorless to greenish glass, also K and Cu enriched, usually forms only thin surface coatings, in places covered by younger melt extruded from pebble interior. Burnt loam is missing. At Grabenstätt-Kaltenbach, a depression of unclear origin was investigated. Morphologically, it matches craters rather than limekilns, but anthropogenic contamination (brick-like material) is probable. The rare molten samples do not display extreme deformation features. The thermally affected stones, mainly those from Emmerting, have elevated magnetic susceptibility.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Public participation is significant for the success of any urban planning project. However, most members of the general public are not planning professionals and may not understand the technical details of a 2D paper-based plan, which might hamper their participation. One way to expand the participation of citizens is to present plans in well-designed, user-friendly and interactive platforms that allow participation regardless of the technical skills of the participants. This paper investigates the impacts of the combined use of 3D visualization and E-participation on public participation in Kisumu, Kenya. A 3D City model, created with CityEngine2016, was exported into a web-based geo-portal and used as a Planning Support System in two stakeholder workshops in order to evaluate its usability. For e-participation, 300 questionnaires given out to planning practitioners. Five indicators were developed for evaluating the usability of the 3D model while the usability of e-participation was evaluated using communication, collaboration and learning as indicators. Results showed that effectiveness and efficiency varies within different professional groups while the questionnaires showed strong preference for e-participation methods, especially SMSs/USSDs and emails. The study concludes that the use of 3D visualization and E-participation has the potential for improving the quality and quantity of public participation and recommends further research on the subject.

Effects of oxygen content on microstructure and creep property of FGH96 superalloy were investigated. When oxygen content increased from 135ppm to 341ppm, prior particle boundary (PPB) rose from degree 2 to degree 3, and the size of γ′ phase on PPB enlarged from 1.07μm to 1.27μm, and MC carbide size grew from 77.4nm to 104.0nm. Meanwhile, the steady creep rate accelerated form 4.34×10-3 h-1 to 1.87×10-2 h-1, and the creep rupture life shortened from 176h to 94h, and the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twins formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries and its micro-twins cross slipped instead of single direction slip in lower oxygen content superalloy. Consequently, specimen with higher oxygen content creeped faster and raptured earlier.

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

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

Predicting human trajectories poses a significant challenge due to the complex interplay of pedestrian behavior, which is influenced by environmental layout and interpersonal dynamics. This complexity is further compounded by variations in scene density. To address this, we introduce a novel dataset from the Festival of Lights in Lyon 2022, characterized by a wide range of densities (0.2-2.2 ped/m2). Our analysis demonstrates that density-based classification of data can significantly enhance the accuracy of predictive algorithms. We propose an innovative two-stage processing approach, surpassing current state-of-the-art methods in performance. Additionally, we utilize a collision-based error metric to better account for collisions in trajectory predictions. Our findings indicate that the effectiveness of this error metric is density-dependent, offering prediction insights. This study not only advances our understanding of human trajectory prediction in dense environments but also presents a methodological framework for integrating density considerations into predictive modeling, thereby improving algorithmic performance and collision avoidance.

More than 1 million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at late stage, either because lack of symptoms such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV) whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer. uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404) a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

One of the main factors that influence the fertility of cattle in grazing systems in hot tropical climates is heat stress. The objective of this study was to evaluate the effect of season, breed, hormonal and physiological condition on the quantity and quality of cumulus-oocyte complexes (COCs) and embryos produced in vitro, from Romosinuano (RM) and Tropical Milking (TM) donors. Three ovum pick-up and in vitro fertilization (OPU-IVF) were performed, one per season; hot dry (HD; 10, 10), hot humid (HH; 9, 9) and fresh dry (FD; 7, 10) in RM and LT donors. Serum levels of cortisol, insulin and glucose were measured, in addition to heart rate (HR), respiratory rate (RR) and rectal temperature (RT). Effect of season x genotype interaction (p≤0.05) was observed in all COCs variables and only in cleavage embryos (CLI) (p≤0.05). Body weight (BW) affected all COCs variables (p≤0.01), except unviable (UNV) although affected degenerated embryos (DEG) (p≤0.01) and total blastocysts (BLAST) (p≤0.01). Cow age only affected viable COCs (VIAB) (p ≤ 0.05), code one blastocysts (BC1) and BLAST (p≤0.01). Cortisol affected total COCs (COCsT), VIAB and total matured in vitro (TMIV) (p≤0.01), as well as CLI, BC1 (p≤0.01) and BLAST (p≤0.05). Insulin affected COCsT (p≤0.01), UNV (p≤0.05), denuded oocytes (DE) (p≤0.01), BC1 and code two blastocysts (BC2) (p≤0.01). Glucose affected all COCs variables (p≤0.01), except UNV and all embryo variables except BC2. HR affected COCsT, DE, TMIV (p≤0.01), CLI, BLAST and DEG (p≤0.05). RR affected COCsT, UNV, VIAB, CLI (p≤0.05), BC1, BLAST and DEG (p≤0.01). RT only affected DE, VIAB (p≤0.01) and BLAST (p≤0.05). The seasonal climatic year variation of Veracruz and changes in physiological and hormonal variables have diverse effects on the cumulus-oocyte complexes and embryos produced by RM and TM donors.

For multi-sensor integrated systems, such as a mobile mapping system (MMS), data fusion at sensor-level, i.e., the 2D-3D registration between optical camera and LiDAR, is a prerequisite for higher level fusion and further applications. This paper proposes a line-based registration method for panoramic images and LiDAR point cloud collected by a MMS. We first introduce the system configuration and specification, including the coordinate systems of the MMS, the 3D LiDAR scanners, and the two panoramic camera models. We then establish the line-based transformation model for panoramic camera. Finally, the proposed registration method is evaluated for two types of camera models by visual inspection and quantitative comparison. The results demonstrate that the line-based registration method can significantly improve the alignment of the panoramic image and LiDAR datasets under either the ideal spherical or the rigorous panoramic camera model, though the latter is more reliable.

Molnupiravir, a prodrug known for its broad antiviral activity, demonstrated efficacy in animal models of Covid-19, prompting clinical trials where initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the rejection of molnupiravir for permanent market authorization in many countries. This report critically assessed 19 studies published in 17 reports that investigated the efficacy of molnupiravir in animal models of Covid-19 with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal Covid-19 models were disproportionately higher than the dose rec-ommended for human use. Specifically, when adjusted for body surface area, half of the doses of molnupiravir used in the animal studies were more than twice as high as the human dose. Addi-tionally, the drug was frequently given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that these design elements in the reported animal studies contributed to a bias favoring molnupiravir, and thus inflated expectations for its efficacy against Covid-19. Addressing these elements may offer avenues to enhance the clinical efficacy of mol-nupiravir for treatment of Covid-19 that include dose increment, early treatment, and admin-istration by inhalation along with use of molnupiravir in antiviral combination therapy.

The abilities of quantitative description of noise are restricted due to its origin and only the statistical and spectral analysis methods can be applied while an exact time evolution cannot be defined or predicted. It emphasizes the challenges faced in many applications including communication systems where noise can play, on one hand, a vital role impacting signal-to-noise ratio but possessing, on the other hand, unique properties such as infinite entropy (infinite information capacity), exponentially decaying correlation function and so on. Despite the deterministic nature of chaotic systems, the predictability of chaotic signals is limited for a short time window putting them close to random noise. In this article, we propose and experimentally verify an approach to achieve Gaussian-distributed chaotic signals by processing the outputs of chaotic systems. The mathematical criteria, on which the main idea of the study is based on, is the Central Limit Theorem which states that the sum of a large number of independent random variables with similar variances approaches a Gaussian distribution. The study involves more than 40 mostly three-dimensional continuous-time chaotic systems (Chua’s, Lorenz’s, Sprott’s, memristor-based, etc.) whose output signals are analyzed according to criteria that encompass the probability density functions of a chaotic signal itself and its envelope and phase, statistical and entropy-based metrics such as skewness, kurtosis, and entropy power. We found that two chaotic signals of Chua’s and Lorenz’s systems exhibited superior performance across the chosen metrics. Furthermore, our focus extended to determining the minimum number of independent chaotic signals necessary to yield a Gaussian-distributed combined signal. The analytic and experimental results indicate that the sum of at least three non-Gaussian chaotic signals closely approximates Gaussian distribution. It allows generation of reproducible Gaussian-distributed deterministic chaos by modeling simple chaotic systems.

Strategic intelligence covers the examination of what impacts and influences the business and the related SWOT analysis, (strengths, weaknesses, opportunities, and threats mapping). Through this research, leaders will be able to properly allocate and re-route resources, identify areas of improvement, and ensure that strategic initiatives are aligned with the organization's mission. Strategic intelligence is, therefore, effective through the use of critical thought and data-driven decisions and seeing the outcomes of different positioned alternatives. It must also form and support a culture of cooperation and open communication within the organizations, stimulating employees' inputs and learning curves. The article's subject is the necessity for strategic intelligence, a crucial competence for leaders, managers, and companies striving to remain competitive, to be utilized and best leveraged in today's volatile and dynamic business contexts. It helps the leadership turn proactive, foresee trends, and make correct, agile decisions that enforce companies' long-term growth and success. This study follows a research design that includes a thorough literature review and bibliometric research, executed via VoSViewer, illustrating the concept of strategic intelligence from a leadership point of view as a driver of competitive advantage. Further, the article points out that the limitations are acknowledged because the literature on the matter is limited, as strategic intelligence is relatively new to the business sector; moreover, more research is required to fully understand and use the potential of strategic intelligence in business growth. By overcoming these limitations and continuing to study this concept, businesses can gain a competitive edge and make informed decisions that fuel their success in an ever-evolving market. As a result, this study contributes to developing strategic intelligence in leadership and business and paves the road for further research and applications of strategic intelligence theories in organizational contexts.

The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

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

Climate change is a global issue that draws widespread attention from the international society. As an important component of the climate system, the water cycle is directly affected by climate change. Thus, it is very important to study the influences of climate change on the basin water cycle with respect to maintenance of healthy rivers, sustainable use of water resources, and sustainable socioeconomic development in the basin. In this study, by assessing the suitability of multiple General Circulation Models (GCMs) recommended by the Intergovernmental Panel on Climate Change, Statistical Downscaling Model (SDSM) and Automated Statistical Downscaling model (ASD) were used to generate future climate change scenarios. These were then used to drive distributed hydrologic models (Variable Infiltration Capacity, Soil and Water Assessment Tool) for hydrological simulation of the Yangtze River and Yellow River basins, thereby quantifying the effects of climate change on the basin water cycle. The results showed that suitability assessment adopted in this study could effectively reduce the uncertainty of GCMs, and that statistical downscaling was able to greatly improve precipitation and temperature outputs in global climate mode. Compared to a baseline period (1961–1990), projected future periods (2046–2065 and 2081–2100) had a slightly decreasing tendency of runoff in the lower reaches of the Yangtze River basin. In particular, a significant increase in runoff was observed during flood seasons in the southeast part. However, runoff of the upper Yellow River basin decreased continuously. The results provide a reference for studying climate change in major river basins of China.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

Aiming at effectively generating safe and reliable motion paths for quadruped robots, a hierar-chical path planning approach driven by dynamic 3D point cloud is proposed in this article. The developed path planning model is essentially constituted of two layers: global path planning layer and local path planning layer. At the global path planning layer, a new method is proposed for calculating terrain potential field based on point cloud height segmentation. Variable step size is employed to improve the path smoothness. At the local path planning layer, a real-time prediction method for potential collision area and a strategy for temporary target point selection is developed. Quadruped robot experiments were carried out in an outdoor complex environment. The experi-mental results verified that, for global path planning, the smoothness of the path is improved and the complexity of the passing ground is reduced. The effective step size is increased by a maxi-mum of 13.4 times, and the number of iterations is decreased by up to 1/6, compared with the traditional fixed step size planning algorithm. For local path planning, the path length is short-ened by 20%, more efficient dynamic obstacle avoidance and more stable velocity planning are achieved by using the improved dynamic window approach (DWA).

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M):alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various disease and also for drug screening.

The survival rate of extracorporeal life support (ECLS) remains overall at 60 %. Research and development is slow, partly due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator (“RatOx”) and shows preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performance over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199.At the maximum possible amount of effective fiber surface and a blood flow of 100 ml/min, the oxygenator performance has been tested to a maximum of 6.27 ml O2/min and 8.2 ml CO2/min, respectively. The priming volume for this the largest fiber module is 5.4 ml, while the smallest possible configuration with a single fiber mat layer has 1.1 ml of priming volume. The novel RatOx ECLS system has been evaluated in-vitro to comply to a high degree with all predefined functionality criteria for rodent sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.