Glial cells provide physical and chemical support and protection for neurons. Secreted neurotrophic factors, scaffolds and vesicles regulate in addition to normal homeostasis, repair following neural tissue injury or degeneration. We previously demonstrated that human CNS glia have revascularization capacity by inducing endothelial cell sprouting and microchanneling driven by glial cell secreted components. The clinical potential of using secreted factors and vesicles generated by glial cells in conditioned media was shown by their re-normalization of pathological blood vessels and 3D tissue wound healing and remodeling capacity. To identify secreted components of glial cells and how CNS and PNS glial cells differentially regulate neural tissue homeostasis, disease and injury response, we developed a novel culture method for various types of glial cells that allow for isolating and characterizing secreted glial components, free of animal factors and contaminants normally associated with serum-based culture conditions. Our culture method will enable to identify secreted components using ultrasensitive RNA, glycoconjugate and protein analysis technologies. The characterization of glial secreted factors involved microchanneling may help in development of new clinical therapies for glial and neural cells or axons to migrate and reform connections.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

The convergence of Class Incremental Learning (CIL) and Machine Unlearning (MU) is a rapidly developing field in machine learning, especially relevant in adaptive and privacy-sensitive environments like finance. CIL enables models to learn new data classes over time without losing previously acquired knowledge, while MU focuses on selectively forgetting specific data to comply with privacy laws or mitigate security risks. In this paper, we examine the theoretical foundations and practical applications of both approaches, particularly in the financial domain. We explore how these two paradigms interact and complement each other, discuss key algorithms, and present examples to illustrate their applications in areas such as portfolio management, fraud detection, and data privacy. Finally, we explore challenges and potential future directions in achieving optimal synergy between CIL and MU.

Metallothioneins are multifunctional proteins implicated in various cellular processes. They have been used as biomarkers of heavy metal exposure and contamination due to their intrinsic ability to bind heavy metals and their transcriptional response to both physiological and noxious metal ions such as cadmium (Cd) and mercury (Hg). In this study, we aimed to clarify the role of iron and reactive oxygen species (ROSs) in the induction of the metallothionein system (Mtt) in the ciliate protozoan Tetrahymena thermophila. We investigated the relative mRNA abundances of the metallothionein genes Mtt1, Mtt2/4, and Mtt5, revealing for the first time their responsiveness to iron exposure. Furthermore, by using inhibitors of superoxide dismutase (SOD) and catalase (CAT), alone or in combination with iron, we highlighted the roles of superoxide ion and endogenous hydrogen peroxide, as well as the complex interplay between the metal and ROSs. These results enhance our understanding of the metallothionein system in ciliates and suggest that ROSs may be a primary evolutionary driver for the selection of these proteins in nature.

IT strategic planning is a critical driver of performance for small and medium-sized enterprises (SMEs), improving operational efficiency, decision-making, and innovation. This systematic review synthesizes findings from eighty studies, highlighting the varied impacts of IT strategic planning on SME performance. Quantitative analysis was used in 45% of studies, while thematic analysis was applied in 25%, showing the growing preference for data-driven insights. Cloud-based solutions, adopted in 11.25% of cases, and hybrid IT setups (17.5%) were identified as key enablers of flexibility and cost-efficiency. SMEs aligning IT strategies with business goals reported up to 20% reductions in operational costs and 15% improvements in customer satisfaction. However, 60% of studies identified resource constraints as a major challenge to IT adoption. Despite these barriers, 60% of studies demonstrated that effective IT planning enhances long-term sustainability and competitive advantage. This review provides actionable insights and strategic frameworks to guide SMEs in optimizing their IT investments for sustainable growth.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H₂Mab-250/H₂CasMab-2. In flow cytometry and immunohistochemistry, H₂Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG₁ version of H₂Mab-250 (H₂Mab-250-hG₁) possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H₂Mab-250-hG₁ and trastuzumab. Both H₂Mab-250-hG₁ and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H₂Mab-250-hG₁. Importantly, H₂Mab-250-hG₁ exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG_2a types of both H₂Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H₂Mab-250-hG₁ and trastuzumab and indicate the future direction for the clinical development of H₂Mab-250-hG₁ against HER2-positive tumors.

We will demonstrate that the photon energy density parameter Ωγ of the universe can be derived exactly in Rh = ct cosmology. We find that it must be Ωγ = 1/5760π ≈ 5.52621330180192× 10^(−5). This indicates that there is no uncertainty in the radiation density within at least somesub-classes of Rh = ct cosmology.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

The presence of the mite, Varroa destructor, requires the use of acaricide treatments in most honeybee colonies. Amitraz is one of the most common acaricide substances used by beekeepers. Some Varroa mite populations have developed resistance to amitraz leading to a loss of efficacy of amitraz-based treatments. Two products, Apivar and Supatraz were applied in the same apiary. Both treatments are amitraz-based but have a different galenics. Thanks to field data, a dynamic model was used to simulate the action of Apivar and Supatraz on the mite population. We consider two parameters to compare the products: daily mortality rate and treatment duration. In the field, the percentage of efficacy between the two products was not significantly different but Supatraz kills mite faster and decreases 90% of the mite infestation in 28.4 days compared to 50.9 days for Apivar. Thanks to modelling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy to stabilize the varroa mite population due to its faster release of active ingredient than Apivar, needing a shorter period to achieve the same result. Depending on the model, Supatraz conserve a good efficacy for low resistant mites but not for high resistant mites. These results show that the comparison of the efficacy of two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.

Traditional chemical research often relies on trial-and-error synthesis and characterization methods. Now, modern machine learning (ML) offers data-driven approaches for predicting properties, like water solubility, directly from chemical structure. But with various data representation schemes for molecular structure and model approaches to select from, it can be difficult for non-experts to determine best practices for utilizing ML. To clarify this landscape of choices, this study uses the ESOL molecular solubility dataset to compare the performance of a selection of different models on different data representations. First, we compare three classical regression methods (linear, ridge, LASSO) on three common data representations (RDKit fingerprint, Morgan fingerprint, intuition-selected molecular features). Then, we demonstrate how two distinct deep learning approaches (multilayer perceptron, graph convolution) can achieve accurate predictions even when prior intuition about feature-property correlations are absent. Finally, we outline a modern attention-based approach, inspired by successes in language modeling and fine-tuned by Bayesian optimization, to achieve a prediction methodology that is more general and performant than the previous approaches. This attention-based approach operates directly on the common SMILES string molecular representation, without requiring as many model parameters as other deep learning approaches or preprocessing into a representative fingerprint or vector of intuitively selected features. In short, when selected molecular features are known to likely correlate with a feature of interest, it may be possible to achieve good predictive modeling without turning to massive deep learning approaches. When particular features are not known a priori, graph approaches are a common solution, and we further demonstrate how a modern hyperparameter optimized attention approach can perform even better.

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken. We found an average bacterial load of 4.24 × 10⁴ CFU recovered/mask, with a maximum load of 2.85 × 10⁵ CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration, and prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.

Background The use of antimicrobials to treat food animals leaves antimicrobial residues in foodstuffs. The World Health Organization (WHO) defines the acceptable daily intakes (ADIs) of these residues as the dose of these antimicrobials that is safe for an average human to consume on a daily basis. We hypothesized that the low dose of ciprofloxacin classified as safe by the WHO could select for ciprofloxacin resistant strains of Klebsiella pneumoniae in a Galleria mellonella model. Objectives We aimed to evaluate if the consumption of peri-ADI doses of ciprofloxacin could select for ciprofloxacin-resistant (Ser464Phe, GyrB, ciprofloxacin MIC of 4 µg/mL) compared to -susceptible (isogenic, ciprofloxacin MIC of 0,047 µg/mL) strains of K. pneumoniae in a Galleria mellonella model. Methods A model of K. pneumoniae infection in G. mellonella larvae was used for the experiment. The larvae were inoculated with K. pneumoniae followed by 10x ADI, 1x ADI, 1/10^th ADI, 1/100^th ADI, 1/1000^th ADI doses of ciprofloxacin. Isolation of K. pneumoniae colonies was then performed on selective agar plates with and without ciprofloxacin (1 µg/mL) plates. The proportion of colonies with ciprofloxacin resistance was then calculated for each group at 24 and 48 hours. Results A significant increase was seen in the proportion of resistance for the 1x ADI and 1/10^th ADI concentration on day 2 compared to the positive control. Conclusion We found that at 48 hours, there was an enrichment of K. pneumoniae colonies with ciprofloxacin resistance in the larvae receiving 1x ADI and 1/10^th ADI concentrations of ciprofloxacin. These results suggest that the ciprofloxacin MSC_select for K. pneumoniae in this model is 1/10^th of the acceptable daily concentration (ADI) dose of ciprofloxacin, which is equivalent to 0.239 ng/µl.

This qualitative research explores Supplier Relationship Management (SRM) within the context of subscription-based e-commerce models. Through in-depth interviews and thematic analysis, the study investigates key elements such as trust, collaboration, technology integration, sustainability, risk management, cultural alignment, innovation, cost management, globalization, supplier selection, and performance measurement. Findings reveal that trust is foundational in fostering reliable interactions and open communication between e-commerce businesses and suppliers. Collaboration emerges as crucial for innovation and operational efficiency, facilitating co-development and shared risk management. Technology integration, including AI and blockchain, enhances supply chain visibility and decision-making capabilities. Sustainability considerations drive businesses to engage with suppliers adhering to environmental standards, enhancing brand reputation and consumer loyalty. Effective risk management strategies mitigate disruptions and ensure supply chain resilience. Cultural alignment fosters harmonious partnerships and mutual understanding across diverse global markets. Innovation through supplier collaboration drives product development and market responsiveness. Cost management practices optimize operational efficiency and strategic supplier relationships. Globalization necessitates adaptive strategies to manage diverse cultural and regulatory landscapes. Strategic supplier selection and continuous performance measurement drive ongoing improvement and alignment with business objectives. This study contributes empirical insights and practical implications for enhancing SRM in subscription-based e-commerce, informing strategies to navigate challenges and leverage opportunities in a competitive marketplace.

BACKGROUND: Scoliosis is a widespread musculoskeletal disorder of bending and twisting of spine. In this medical ailment, spine curves to the side and even in severe cases it can twist and can take several bends. For the diagnosis and treatment of scoliotic patients, the Cobb’s angle is a critical marker of the body’s curvature. OBJECTIVE: There are many researches that have been conducted to automate the manual measurement of the angle and every investigation has their own limita- tions. METHODS: This paper presents a method for precisely measuring the Cobb’s an- gle using deep learning based techniques. Mainly it comprises of feature enhance- ment of augmented dataset, a bespoke code for landmark estimation on the spine, segmentation model based on the U-Net architecture and a custom code for Cobb’s angle measurement. These measured angles are then compared to the given angles for the segmentation on biomedical (X-ray) images. RESULTS: The findings demonstrate that the proposed technique offers an auto- mated and impartial way for precisely measuring this angle with an overall accu- racy of 97% and Root Mean Square Error (RMSE) of 4.99, which can lower the variability, facilitate early detection, accurate diagnosis, and monitoring of scolio- sis progression. Additionally, it aids in the treatment planning and evaluating treat- ment outcomes. CONTRIBUTION: By leveraging the applications of Cobb’s angle measurement, healthcare professionals can enhance the quality of care and can improve long-term outcomes for individuals with scoliosis.

Introduction and importance: Congenital bicuspid aortic valve (BAV) is a common cardiac malformation predisposing individuals to aortic stenosis, regurgitation, and aortopathy. This risk persists even after aortic valve replacement (AVR). Case presentation: We report a case of a male in his 60s with a history of BAV who underwent bioprosthetic aortic valve replacement (BVR) and ascending aorta/root repair in 2014. The patient was noncompliant with follow-up and presented nine years later with severe bioprosthetic aortic stenosis and an 8.0 cm ascending aortic aneurysm with no symptoms. Emergent redo BVR and aneurysm repair were successful. Clinical discussion: It should be emphasized that successful outcomes for BAV patients require a lifelong commitment to surveillance, even after surgical intervention. Noncompliance can lead to life-threatening consequences like bioprosthetic valve deterioration or progressive aortic dilation. Conclusion: This case highlights the importance of early BAV diagnosis for ongoing monitoring, accessible follow-up care after complex cardiac procedures, and addressing patient barriers to treatment adherence.

Vitamin D deficiencies are very common in pregnant women, raising concerns about adverse health outcomes in children. This issue has hardly been studied in multiple pregnancies, the prevalence of which has been steadily increasing. Therefore, our study investigated the relationship between newborns’ anthropometric parameters and the concentration of 25(OH)D in maternal blood of women with twin pregnancies and umbilical cord blood. The study included 50 women who gave birth after the 36th week of twin gestation. 25(OH)D was determined in maternal blood collected during the antenatal period and in the umbilical cord blood of 100 newborns. Anthropometric parameters of the newborns (birth weight, length, head and chest circumference) were obtained from hospital records. Data on nutrition and lifestyle during pregnancy were collected from the patients during an interview conducted by a dietitian. No relationship between maternal and neonatal cord blood vitamin D concentrations and any of the anthropometric parameters of the newborns was found. However, only 6% of the mothers and 13% of the newborns had vitamin D deficiency (≤20 ng/mL). The type of pregnancy and maternal height were the main factors associated with neonatal size. Newborns from dichorionic pregnancies were on average 202 g heavier (p<0.001) and 1 cm longer (p=0.006) than newborns from monochorionic pregnancies. Newborns of mothers ≤ 160 cm in height had on average 206 g lower birth weight (p=0.006) and were 3.5 cm shorter (p=0.003) compared to newborns of taller mothers. Therefore, in our study, neonatal size of the twins was not related to the vitamin D status but to other factors such as the type of pregnancy and maternal height.

Emerging molecular and computational techniques may allow construction and computational treatment of dynamic digital twins on the scale of populations to individuals. This approach may pave the way for predictive, preventive, and personalized treatment. Because digital twins are independent of geographical location, this may also contribute to global equitable health.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

The unravelling of the human genome created new perceptions on the origin and evolution of diseases and for cancer in particular, it established the notion that neoplasia has been a companion of life since its ap-pearance on earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today, begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century, generate new ther-apeutic opportunities with immunotherapy, oncolytic virotherapy and gene transfer, the latter especially in cases of hereditary cancer.

This study explores the relationship between positive and negative habits and their rewards over time. Using a bibliographic and documentary approach, we analyze how the temporality of rewards influences the formation and maintenance of habits. We developed the "habit chart", which shows that positive habits, such as reading, healthy eating, physical exercise, meditation and personal relationships, offer incremental and lasting rewards. In contrast, negative habits such as sugar consumption, excessive use of social media and a sedentary lifestyle provide immediate gratification followed by a sharp decline. The analysis was based on studies such as those by Warburton et al. (2006), Lally et al. (2010), and Hu (2003) for positive habits, and Malik et al. (2010) and Kross et al. (2013) for negative habits. We conclude that practical strategies, such as financial incentives and creating enabling environments, can make long-term rewards more tangible, promoting the adoption of healthy behaviors. This study reinforces the importance of the temporality of rewards in habit formation and suggests evidence-based interventions to improve quality of life and general well-being.

Passive marine listening, involving the acoustic monitoring of underwater environments, has become increasingly vital for scientific research, environmental monitoring, and defense applications. However, the success of such applications critically depends on the ability to extract meaningful information from the often noisy and dynamic underwater acoustic environment. In this context, Mel-frequency cepstral coefficients (MFCCs) have emerged as an essential tool for feature extraction, capturing the spectral characteristics of marine sounds and making them ideal for species identification and sound event detection. This research presents an innovative approach to enhance the robustness of MFCC-based passive marine listening through adaptive noise reduction techniques. The proposed approach utilizes dynamic spectral subtraction to counter underwater noise, resulting in enhanced signal-to-noise ratios for desired sounds. This adaptive system adjusts to dynamic underwater noise, allowing it to concentrate on target sounds and suppress interference effectively. The experimentation further validates the effectiveness of the proposed approach, with results reaching 99% on the full dataset of 570 mammals and vessels, demonstrating the effectiveness of SVM and Random Forests in the classification of underwater audio.

We will outline the relationship between luminosity distance and cosmological redshifts, demonstrating that it is consistent with a new cosmological model recently proposed by Haug and Tatum [1], which appears to resolve the Hubble tension within the Rh = ct cosmology.

A new data processing method based on Machine Learning (ML) algorithms has been developed and tested in clinical environments during COVID-19 trials at the Medical University of South Carolina (MUSC). Breath samples have been collected in 2020–2021 from 100 participants using gas chromatography combined with ion mobility spectrometry (GC-IMS, G.A.S. mbH). Polymerase chain reaction (PCR) tests combined with clinical diagnostics were used as a reference method. Once the ML training-testing cycle is completed, the diagnostics of a single data set may be completed in as little as a few seconds. A convincing difference in the Volatile Organic Compounds (VOS) breath biomarker signature with COVID-19 positive and negative participants has been found. This approach is a generic method that can be applied to data sets collected with other types of hardware, e.g., different settings of GC, GC-MS, GC-GC, or other methods providing high information density in 2-dimensional data sets.

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

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

Artifact metrics is a technology for authenticating artifacts based on their unique characteristics. The artifact-metric system offers "clone resistance," i.e., it makes it highly improbable to create another object exhibiting the same measured values as a genuine artifact. However, determined adversaries may still attempt to create imitations or clones with close physical characteristics to those of registered products, even if they cannot perfectly replicate the genuine product. Such clones serve to deceive users into believing they are genuine rather than counterfeits. Thus, in this study, we consider a scenario in which we measure raster-scanning-generated clones via a non-raster scanning method. Further, we employ image processing techniques to generate image data representing the clones and theoretically assess the filtering effects on these images. Our findings reveal that applying filters to specific frequency components in the spatial frequency domain can effectively highlight differences between raster-scanning-created clones and the corresponding genuine artifacts. Thus, we demonstrate directional emphasis filtering in artifact metrics as an effective approach for rejecting raster-scanning-created clones.

This article explores the use of vegetation indices (VIs) in remote sensing for estimating standing wood volume and volume increments in forest ecosystems. The study investigates the correlations between various VIs and wood volume across different forest stand age classes, focusing on the effectiveness of commonly used indices such as Squared Ratio Simple Red Edge (SQSR) and Red-Edge Ratio Vegetation Index (RERVI), as well as other typical indicators including Enhanced Vegetation Index (EVI), Red-Edge EVI (RE-EVI), and Green Normalized Difference Vegetation Index (GNDVI). Additionally, the analysis considers a pair of indicators based on blue and near-infrared channels, resembling the Blue-normalized Difference Vegetation Index (BNDVI). The research reveals that quadratic and power-law models of SQSR and RERVI demonstrate higher correlations (>0.40) with wood volume, especially in younger forest stands (>0.80). Furthermore, the study highlights the potential of NDII and NDWI indices for estimating volume increments in certain classes of forest stands (0.70). However, correlations vary across different forest stand classes, suggesting the need for further investigation into the reliability of VIs for monitoring wood volume and volume increments in forest ecosystems. Overall, this research contributes to the understanding of the applicability of VIs in remote sensing for forest management and ecosystem monitoring.

Sodium valproate is a established antiepileptic drug of first choice, primarily used to treat epilepsy, but also bipolar disorder and prevent migraine headaches. Valproate increases concentrations of gamma-aminobutyric acid in the brain, due to inhibition of enzymes responsible for the catabolism of gamma-aminobutyric acid. Main goal of this research consisted in the optimization and development for a new sensitive spectrophotometric quantitative analysis method of sodium valproate from tablets in the Visible field. Following the quantitative color reaction of sodium valproate with diazonium salt of alpha naphthylamine in alkaline medium, a light yellow azo dye was formed and spectrophotometrically analyzed at the wavelength of 386 nanometers. The amount of pure sodium valproate found on pharmaceutical extended-release tablet was 492.578 miligrams compared to the official declared pure amount of 500 miligrams on prolonged-release tablet. Amount found was assigned to a percentage content of 98.5156 percent pure sodium valproate in a pharmaceutical tablet. Mean average percentage error (deviation) from the officially stated value was about 1.4844 percent, which was included within normal limits, below five percent maximum limit allowed by European and Romanian Pharmacopoeias rules. Spectrophotometric method was subjected to the statistical validation procedure and was successfully validated.

Color change is the most obvious characteristic of tomato ripening stage and an important indicator of tomato ripening condition, which directly affects the commodity value of tomato. To visualize the color change of tomato fruit in mature stage, a gated recurrent unit network with an encoder-decoder structure that dynamically simulates tomato growth and development with time-dependent lines using tomato color and shape as real-time data was proposed in this paper. Firstly, the .json file was converted into a mask.png file, the tomato mask was extracted, and the tomato was separated from the complex background environment, and the tomato growth and development data set was successfully constructed. Then, a network of gated recurrent units with encoder-decoder structure was constructed to predict the future growth trend of tomato under different greenhouse temperatures. The experimental results showed that for the gated recurrent unit network of encoder-decoder structure proposed, when the hidden layer number was 1 and hidden layer number was 512, a high consistency and similarity between the model predicted image sequence and the actual growth and development image sequence would be realized, and the structural similarity index measure was 0.746. It was proved that when the average temperature was 24.93℃, the average soil temperature was 24.06℃, and the average light intensity was 11.26 Klux, the environment was the most suitable for tomato growth. The environmental data-driven tomato growth model was constructed to explore the growth status of tomato under different environmental conditions, thus to understand the growth status of tomato in time. The statement provided a theoretical foundation for determining the optimal greenhouse environmental conditions to achieve tomato maturity. And it offered recommendations for investigating the growth cycle of tomatoes, as well as technical assistance for standardized cultivation in solar greenhouses.

Based on the nonlinear failure criterion and modified tangential technique, the upper bound solutions of supporting pressure on the deep tunnel face were obtained under pore water pressure conditions. The influence of parameters on the supporting pressure and collapse range was investigated according to the unlimited block failure mechanism. It is found that the upper bound solutions of supporting pressure increase with the growth of the nonlinear coefficient and pore water pressure coefficient. The collapse range of the tunnel face scales out with the increase of the nonlinear coefficient and shrinks when increasing the pore water pressure coefficient. Moreover, with the increase of the nonlinear coefficient, the impact strength on supporting pressure and collapse range declines gradually. According to the calculating results, it is manifest that both the pore water pressure and nonlinear criterion factors have negative impacts on the stability of the tunnel face. Thus, more attention should be paid to these parameters to ensure face stability in deep tunnel construction.

Timely screening for breast cancer plays a pivotal role in early detection and treatment; however, Afghan refugee females face significant barriers that hinder their access to these life-saving screening services. Cultural norms, socioeconomic factors, proficiency with the English language, and the challenges of navigating foreign healthcare systems contribute to low screening rates within this population. The current review article seeks to identify barriers to breast cancer screening in the Afghan refugee population in the United States (US) and address possible measures to overcome these challenges.

We use the Stefan-Boltzmann law to derive and investigate what we will call the black hole CMB temperature luminosity. Interestingly, the CMB luminosity is always the same for every black hole at a luminosity distance equal to the Schwarzschild radius, which is fully valid in black hole cosmology, a topic that is actively discussed to this day. The CMB black hole luminosity is always the same , regardless of the mass of the black hole. This is in contrast to the Bekenstein-Hawking luminosity, which is linked to the Hawking temperature, that is mass dependent.

This study investigates the application of deep residual networks for predicting the dynamics of interacting three-dimensional rigid bodies. We present a framework combining a 3D physics simulator implemented in C++ with a deep learning model constructed using PyTorch. The simulator generates training data encompassing linear and angular motion, elastic collisions, fluid friction, gravitational effects, and damping. Our deep residual network, consisting of an input layer, multiple residual blocks, and an output layer, is designed to handle the complexities of 3D dynamics. We evaluate the network's performance using a dataset of 10,000 simulated scenarios, each involving 3-5 interacting rigid bodies. The model achieves a mean squared error of 0.015 for position predictions and 0.022 for orientation predictions, representing a 25% improvement over baseline methods. Our results demonstrate the network's ability to capture intricate physical interactions, with particular success in predicting elastic collisions and rotational dynamics. This work significantly contributes to physics-informed machine learning by showcasing the immense potential of deep residual networks in modeling complex 3D physical systems. We discuss our approach's limitations and propose future directions for improving generalization to more diverse object shapes and materials.

In this article, we investigate both the Schrödinger and continuity equations in the presence of nonlocal potential that arising from electron-electron interaction and local one in the context of minimal uncertainty in momentum within commutative and noncommutative frameworks. Furthermore, the Frahn–Lemmer potential type is used. Interestingly, the combined effects of both the phase-space noncommutativity and nonlocality on the current density while considering a minimal uncertainty in momentum are examined. We find that the current density, as conventionally defined, does not fulfil the condition of current conservation, thus, a new definition of the current density that encompasses the aforementioned contributions is given. Thereafter, it is shown that the computed current using the new definition of the current density satisfies the current conservation. Noting that using both the $★$product and linear Bopp-Shift, the noncommutativity is inserted.

Introduction: Parameters used for neonatal mortality calculation vary among publications. Mortality in < 33 weeks gestational age at birth display global variations across different healthcare units. Objective: This study aims to explore trends in neonatal mortality among infants born preterm in the different units in Latin America and the Caribbean utilizing the EpicLatino Network Database in comparison to Canadian Neonatal Network (CNN) 2022. Materials and Methods: This study focused on an eight-year period, with a particular attention to mortality rates during the pre-pandemic (2015-2019) and pandemic/post pandemic (2020-2022) periods. Survival rates from CNN 2022 were included in the comparison analysis. Logistic regression analysis was confined to the 2020-2022 period. Adjustments were made for factors including gestational age, small for gestational age (SGA), Snape II score, inborn/outborn status, and center. As major malformations could account for mortality differences among units. The incidence of major congenital malformations, as defined by CNN, was compared among deceased patients. Results: A total of 15,454 records from 2015-2019 and 10,711 records from 2020-2022 were scrutinized. Overall, there were no significant differences in mortality rates between the two time periods (p=0.22). Moreover, the originating unit during the 2020-2022 period significantly influenced all statistical computations. Conclusions: Survival rates among infants < 26 weeks of gestation in Latin America and the Caribbean are on an upward trajectory, with the healthcare unit playing a pivotal role in this outcome within the EpicLatino database. Major malformations do not seem to be a significant contributing factor. These findings underscore the imperative of implementing quality improvement initiatives to elevate neonatal care standards in Latin America and the Caribbean.

Within education, we make assumptions the correct manner of teaching a student, and with that, we assume further that regardless of the intellectual content that a student should engage with, the acculturation for the customary (and always rather traditional) means of religious apprehension for the purpose of an assumedly universal and beneficial role. This article instead promotes the view that such determinations are (1) unsuitable for modern society and (2) causal to a disjunction with a truly proper manner of education in the form of the matheticism – a term rather unfortunately applied in educational theory.

“Energy” is probably the most important term in science and technology. The reason is energy can be converted while it is overall conserved, and thereby correlates changes of a wide variety. Despite its successful use in many areas over more than a century, an analysis of current literature shows that definitions of what energy is and explanations why it is conserved are inconsistent. With regard to energy forms not even a definition was found, and examples given are often wrong. Looking at two interacting objects in the most simple situations, with energy conservation but without conversion, a consistent understanding of energy and its conservation can be derived. Based on it, the systematic set of energy forms with a clear definition of each is then presented.

Star copolymer films were studied for confirming the role of film morphology in antimicrobial activity previously reported. With this scope, films of a two-branches copolymer, namely m-PEG-(MMA-ran-DMAEMA)2, containing ≈ 40 % in mol of non-quaternized 2-(dimethylamino)ethyl methacrylate, were produced by using spin-coating, drop-casting and casting deposition techniques, thus obtaining ultra-thin, thin and thick films, respectively. The morphology is generally flat for thin and thick films, but it becomes substrate dependent for ultra-thin films where the film planarization effect is not efficient. Mechanical properties of such films were investigated by Force Volume Maps in both air and liquid. In air, ultra-thin films are in the substrate-dominated zone and thus the elastic modulus E is overestimated, while E reaches its bulk value for thin and thick films. In liquid (water), E follows an exponential decay for all films with a minimum soaked time t0 of 0.37 and 2.65 h for ultra-thin and thin and thick films, respectively. After this time, E saturates to a value in average 92 % smaller than that measured in air due to films swelling. Such results confirm the role of morphology envisaged in literature, suggesting also an additional role of mechanical properties in the antimicrobial activity.

According to Young Minds [1] ‘everyone gets angry sometimes’. Their website offers a number of de-escalating strategies, including staying calm, managing responses and setting limits to help young people who most deem resistive. Yet, Young Minds are not alone because such logical advice is ubiquitous in the literature about challenging behaviour despite the fact that in our experience when faced with high states of arousal, most young people tend to act first and deal with the consequences later. It’s not that they are stupid or non-caring, but they are human capable of great feats as well as stupidity. The same is true for any claims that solution focused (SF) conversations can put right the several decades of psychological theory suggesting resistance requires logic and better cognition. By giving the correct thinking skills, young people will walk away from risk, avoid physical confrontation, handle challenging situations like logical thinkers, and generally discount that the process of growing up is part of the challenge. It is with this in mind that over recent years in our current SF practice (with staff group supervision) we have examined the concept of ‘resistance’ and how it can be put to use as a process of collaboration. To do this, we have revisited SF theory that preoccupied many of its pioneers during the 1980’s and 1990’s and attempted to make it useful for the early 2020’s for professionals having conversations with young people, who, in traditional models, are labelled challenging. We want to introduce key differences of solution focused practice and how Anita started to formulate a 6D-SF model (details, dynamics, dimensions, dispositions, dislocations, descriptions) for contemplating how groups of professionals relate to each other and are triggered by challenging behaviour. We do not claim to have proof, logic or exactness on our side, but we’re happy to suggest how our resistance mirrors what many of the staff teams feel and describe when working through their work.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

There are evidences of shared biological mechanisms between obesity and hypertension during childhood in the adulthood, and loads of research literatures have proven that, it will cost the economies and health of nations profoundly if neglected. The Prevention and early diagnosis of cardiovascular risk factors such as overweight and hypertension is an essential strategy for control, effective treatment and prevention of its’ complications. The aim of the study is to assess the effect of school based Exercise and Life style Motivation Intervention (SEAL-MI) on adolescent's cardiovascular risk factors and academic performance. An experimental study was conducted among 1005 adolescents - 520 and 485 adolescents were randomly selected for control and study group, respectively. Demographic details and the data related to dietary habits, physical activity and sleep quality were collected by a structured interview questionnaire. The study group adolescents were given the SEAL-MI for six months which includes a school based rope exercise for 45 minutes per day for 5 days a week and a motivation intervention related to dietary habits, physical activity and sleep. Post-test 1 and 2 were done after 3 and 6 months of intervention. The prevalence of overweight among adolescents was 28.73% and prehypertension was 9.26%. Among overweight adolescents, the prevalence of prehypertension was found to be very high (32.25%). In post intervention, there was a significant reduction in weight, BP (p=0.000) and improvement in dietary habits, physical activity, sleep (p=0.000) and academic performance. A significant positive correlation was found between BMI and SBP (p=0.000) and BMI and academic performance (p=0.003). The linear regression analyses revealed that the gender (ß: 0.47, 95% CI: 0.39, 0.81), age (ß: 0.39, 95% CI: 0.17, 0.46), family income (ß: 0.2, 95% CI: 0.41, 0.5), residence (ß: 0.19, 95% CI: 0.01, 0.27) and type of family (ß: 0.25, 95% CI: 0.39, 0.02) had the strongest correlate with the BMI of the adolescents. Also, Mother’s education Mother’s education (ß: 0.35, 95% CI: 0.18, 0.59) had the strongest correlate with the SBP of the adolescents. In contrast, the DBP was negatively persuaded by age (ß: -0.36, 95% CI: 1.54, 0.29) and gender (ß: -0.26, 95% CI: 1.34, 0.12) of the adolescents. Regular practice of rope exercise and lifestyle modification such as diet, physical activity and sleep quality among adolescents prevent and control childhood CVD risk factors like overweight, hypertension. The SEAL-MI may lead to age appropriate development of adolescents and improves their academic performance and quality of life. Giving importance to the adolescents from urban habitat, from affluent nuclear family and catching them young will bring significant change in the disease burden.

Keywords: Response surface methodology; Ultrasonication; marigold flower; polyphenols, microcapsules; antimicrobial activity.

Teledermatology, the dermatological consultation and diagnosis via digital communication technologies, has become increasingly important in modern healthcare. The integration of teledermatology into clinical practice has gained significant interest, especially during the COVID-19 pandemic. Numerous studies have shown the effectiveness and reliability of teledermatology, with high levels of patient satisfaction and diagnostic accuracy. Pathpoint® eDerma is a cloud-based dermatology platform that aims to streamline the documentation and management of dermatological conditions. It offers several clinical benefits, including faster diagnosis, reduced unnecessary procedures, improved access to care, and cost savings. The platform follows a comprehensive risk management plan and complies with safety regulations. It undergoes regular recertification and reviews to ensure its safety and effectiveness. The clinical evaluation of eDerma confirms its ability to deliver significant clinical benefits while effectively mitigating risks. The benefit-risk ratio of eDerma is highly acceptable, supporting its use in clinical settings to enhance dermatological care.

Adamantinomatous Craniopharyngioma (ACP) is a rare epithelial tumor located in the craniopharyngeal duct, often associated with high morbidity and a high long-term recurrence rate. ACP is predominantly diagnosed in children below the age of 15 and accounts for a majority of Craniopharyngioma cases in the United States. It is most commonly caused by a mutation in exon 3 of the CTNNB1 gene, which promotes overaccumulation of β-Catenin in the WNT pathway. As β-Catenin accumulates, it over-activates the transcription factor, causing an over-transcription of WNT proteins and uncontrolled cell growth. Current methods of treatment for ACP are centered around surgical intervention and radiotherapy, including gross-total resection (GTR), subtotal resection (STR), and a combination of subtotal resection and adjuvant radiotherapy (STR+XTR). These methods of treatment are associated with high risk due to the proximity of ACP to critical structures near the craniopharyngeal duct. High recurrence rates and morbidity are closely associated with current methods of treatment and other methods have yet to be attempted in craniopharyngioma. This review will explore two possible methods of non-surgical and non-radiological therapeutic interventions. The use of RNAi therapy and CRISPR may provide insight and be a potential way to treat ACP with increased quality of life and decreased recurrence rates.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Asphaltene precipitation and deposition pose significant operational challenges in both reservoirs and surface facilities by inducing formation damage. To understand the kinetics involved in asphaltene particle nucleation, growth, and aggregation, this study employed confocal microscopy and centrifuge-based methods under a unified set of experimental parameters. The acquired time-resolved particle size images were analyzed using MIPAR image processing software, while asphaltene mass yield was quantitatively evaluated through centrifugation. Experimental conditions were varied to study the effects of heptane concentration, asphaltene concentration, and shear rate. Notably, this investigation introduces, for the first time, the parameter of particle count as an additional variable influencing asphaltene mass production. This study aims to discern how particle count correlates with asphaltene mass yield over time. Results indicate that the minimum mean particle diameter was observed to be 2 microns, which progressively grew up to 80 microns. The mean particle diameter exhibited a positive correlation with both asphaltene concentration and shear rate, whereas an inverse correlation was seen with heptane concentration. Furthermore, the asphaltene mass yield was found to increase with greater asphaltene and heptane concentrations, as well as with higher shear rates. The relationship between mean particle diameter and mass yield was found to be nonlinear. In the early stages, a higher prevalence of small particles contributed to a greater total particle count, while at later stages, particle aggregation led to the formation of larger particles that influenced the overall asphaltene mass. The insights gained from understanding the relationship between particle diameter, count, and mass yield are crucial for advancing the fundamental science of asphaltene precipitation and deposition. These findings may also guide future research that relies solely on particle counts for assessing asphaltene deposition.

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

Human number understanding is thought to rely on the analogue number system (ANS), working according to Weber’s law. We propose an alternative account, suggesting that symbolic mathematical knowledge is based on a discrete semantic system (DSS), a representation that stores values in a semantic network, similar to the mental lexicon or to a conceptual network. Here, focusing on the phenomena of numerical distance and size effects in comparison tasks, first we discuss how a DSS model could explain these numerical effects. Second, we demonstrate that DSS model can give quantitatively as appropriate a description of the effects as the ANS model. Finally, we show that symbolic numerical size effect is mainly influenced by the frequency of the symbols, and not by the ratios of their values. This last result suggests that numerical distance and size effects cannot be caused by the ANS, while the DSS model might be the alternative approach that can explain the frequency-based size effect.

The forest regeneration phase in Sweden commonly involves mechanical soil preparation followed by planting of Scots pine or Norway spruce seedlings. The prepared soil offers planting positions with different properties, including decreased damage by pine weevil (Hylobius abietis L.). Nitrogen fertilization can be applied at the time of planting to aid establishment of the seedlings. In this study we compared the effect of organic nitrogen-fertilization for different planting positions, and seedling sizes on early survival and growth of Scots pine and Norway spruce seedlings. The main planting positions were capped mound, hinge, and mineral soil. Seedlings planted close to organic material were categorized as “low quality positions”, since proximity to organic material increase pine weevil attraction. Higher mortality rates related to pine weevil damage were recorded for seedlings planted in the low-quality positions, regardless of seedling size or N-fertilization. Pine weevil attack rates increased with increasing seedling size. Growth was in general lowest in mineral soil positions. The effect of organic N-fertilization on growth was positive for spruce regardless of planting positions and seedling size, while depending on planting position and seedling size for pine, indicating that effects of organic N-fertilization depend on seedling species, -size and planting position.

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

This article comprehensively explores multiple aspects of cryptocurrencies and their price forecasting. Firstly, the article introduces the definition of cryptocurrency and its development process on a global scale, especially focusing on the launch of Facebook Libra and China's central bank digital currency, highlighting the importance and influence of digital currency in the global financial market. Subsequently, the article analyzes the advantages of digital currencies over traditional currencies, including improving economic transaction efficiency, reducing transaction costs and enhancing transaction transparency. Meanwhile, the article also explores the challenges and risks potentially brought by the development of digital currencies, such as regulatory uncertainty and market volatility. In this context, the article raises the importance of cryptocurrency price forecasting and introduces the forecasting models and techniques commonly used today. Finally, through specific experimental analysis, the effectiveness of using the deep learning model CNN-LSTM to predict the price of Bitcoin is demonstrated, and the directions of future research and optimization strategy are proposed. In summary, this paper comprehensively presents the research status and prospects of cryptocurrency and its price prediction field through systematic introduction and analysis.

Abstract: Social media has become a vital tool in ensuring productivity among Undergraduates, as studies have shown an increased number of users globally. This study assessed the impact of social media usage on undergraduates’ academic performance and working memory. Participants from three different universities such as the University of Georgia (UG), Eastern European University (EEU), and Batumi State University (BSU) completed this study using online google forms. UG and EEU are in the capital city, and BSU is in Batumi City. The study questionnaires were approved by the institutional review board before the data collection. Descriptive analyses were assessed for all study populations, characteristics, frequencies, percentages, means, and standard deviations using Statistical Package for Social Science (SPSS Inc., Chicago, IL, version 25.0 for Windows) software. 41.3% were male students, as most of the participants were foreign students living and studying in Georgia. Male students had the risk of ‘conflict’ with families and friends because of social media. Female students are at increased risk of using social media as an ‘escape’ from negative feelings. 89.7% of students that perform physical activities, considering their academic workload had the risk of preoccupation complaints. 87.9% felt dissatisfied regularly because they wanted to spend more time on social media. Utilization of social media differed based on the characteristics of the participants such as age, gender, and geography. We observed the increase in prevalence of social media addiction, its effect on academic performance and working memory among undergraduate students.

Phase errors in magnetic resonance (MR) techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI), pose significant challenges to data accuracy and interpretation. As MR technologies advance, the demand for more sophisticated phase correction methods continues to grow, enhancing diagnostic precision and analytical outcomes. This review explores the evolution of phase correction models, beginning with simple global phase shifts, progressing through traditional linear statistical models, and culminating in modern machine learning techniques—specifically, neural networks. We also examine a range of optimization functions and optimizers, including both MR data-specific and common statistical approaches, applied in phase error correction. Despite notable progress, challenges remain in developing fully automatic phase error correction methods, particularly given the absence of ground truth in real-world MR data. This review highlights key methods, discusses their limitations, and proposes future pathways, including ensemble learning, that could guide further innovation in phase error correction.

The Dual-Frequency Precipitation Radar (DPR) on the Core GPM satellite provides spaceborne 3-dimensional observations of the precipitation field and surface rainfall rate with quasi global coverage. The present study evaluates the behavior of liquid precipitation intensity, radar reflectivity factor (ZKu and ZKa) and Drop Size Distribution (DSD) parameters (weighted mean diameter Dm and intercept parameter Nw) of the GPM DPR derived products version 07 from 2014 to 2023. Observations from seven Parsivel disdrometers located in different topographic zones in the Western Mediterranean are taken as ground reference. Four matching techniques between satellite estimates and ground level observations were tested, and best results were found for the so-called optimal comparison approach. Overall, GPM DPR products capture well the variability of the observed DSD at different rainfall intensities. However, overestimation of the mean Dm and underestimation of the mean Nw are observed, being much more sensitive to errors in drop diameters larger than 1.5 mm. Moreover, lowest errors were found for radar reflectivity factor and Dm, and highest for Nw and rainfall rate. In addition, the GPM DPR convective and stratiform classification was tested and it was found a substantial overestimation of stratiform cases compared to disdrometer observations.

In this note we prove that the Riemann hypothesis is false. The proof is by contradiction based on a criterion of Hu.

Conventional tutoring approaches are confronted with limitations such as restricted availability, inconsistent pedagogical quality, and scalability con-straints. Furthermore, the exclusive use of Large Language Models (LLMs) like ChatGPT in education has its shortcomings, including the potential for incorrect responses and the lack of customized guidance aligned with specific course con-tent. This research proposes an innovative intelligent chatbot tutoring system, in-tegrating the Retrieval Augmented Generation (RAG) approach with a custom LLM. The developed system aims to overcome the limitations of traditional tu-toring and general-purpose LLMs by providing accurate, contextually relevant, and personalized assistance, thereby enhancing student understanding and en-gagement. The system, powered by an intelligent agent, retrieves relevant information from curated academic sources, incorporates interactive features for user feedback, and utilizes machine learning algorithms for ongoing performance enhancement, ensuring a robust and effective tutoring experience. The anticipated outcome is an enriched educational experience for university students, advance-ment in personalized learning, and improved student engagement, retention, and academic performance. Through continuous research and refinement, it is expected that the intelligent chatbot tutor will assume an important role in enhancing and supporting the educational journey of students.

Orificed Hollow Cathodes are electric devices necessary for the functioning of common plasma thrusters for space applications. From their reliability mainly depends the success of a spacecraft’s mission equipped by electric propulsion. The development of plasma models is crucial in the evaluation of plasma properties within the cathodes that are difficult to measure due to the small dimensions. Many models, based on non-linear system of plasma equations, have been proposed in the open literature. These are solved commonly by means of iterative procedures. This paper investigates the possibility to solve them by means of Particle Swarm Optimization method. The results of the validation tests confirm the expected trends for all the unknowns; the confidence bound of the discharge current as function of mass flow rate is very narrow (2÷5V), moreover the results match very well the experimental data except at the lowest mass flow rate (0.08mg/s) and discharge current (1A), where the computations underpredict the discharge current to the utmost by 40%; the highest data dispersion regards the plasma density in the emitter region (± 20 % of the average value) and the wall temperatures (± 50K respect to the average values) of orifice and insert; those of the others variables are very tiny.

The construction sector is a paradigm shift into the sustainable era to solve environmental issues, combat global warming. And the reflection of this is on Green Buildings where energy savings, cost savings, occupant comfort takes priority. The idea of green building efficiency merges sophisticated technologies, creative architectural design templates, and reusable materials into the whole life cycle of a building process in order to render minimum environmental impact. The pilot project of The National Institute of Geophysics and Volcanology (INGV) - Irpinia headquarters, illustrates in this context, innovative technologies of energy transition with a photovoltaic parking with geothermal piles. The project is consistent with the concepts of Nearly Zero Energy Buildings (NZEBs), directed to a high energy performance and very low environmental impact. Incorporating geothermal piles is a major area of advancement in sustainable building ideas that use the Earth's natural heat to create an energy efficient solution in heating and cooling. Project Goals – The project aims to install emission free renewable cleaning energy cost-effective clean production and increase energy efficiency, reduce CO2 emissions and energy security. For this purpose this paper, using as a support the PVGis software, evaluates the potential produced with the photovoltaic system installed in the canopies. With the help of this analysis, it is feasible to determine the amount of electricity produced as well as the system's amortization based on the excess energy sent to the public grid. The project is regarded as creative from the standpoints of energy given the use of geothermal and photovoltaic systems, as well as from an architectural and design perspective due to the use of novel materials. This all-encompassing strategy establishes INGV as a pioneer in the promotion of environmentally friendly technologies and shows a dedication to sustainability and energy efficiency.

We experimentally demonstrate waveguide and microring resonator (MRR) polarizers by integrating 2D graphene oxide (GO) films onto silicon (Si) photonic devices. The 2D GO films with highly anisotropic light absorption are on-chip integrated with precise control over their thicknesses and sizes. Detailed measurements are performed for the fabricated devices with different GO film thicknesses, coating lengths, and Si waveguide widths. The results show that a maximum polarization-dependent loss (PDL) of ~17 dB is achieved for the hybrid waveguides, and the hybrid MRRs achieved a maximum polarization extinction ratio (PER) of ~10 dB. We also characterize the wavelength- and power-dependent response for these polarizers. The former demonstrates a broad operation bandwidth of over ~100 nm, and the latter verifies performance improvement enabled by photo-thermal changes in GO films. By fitting the experimental results with theoretical simulations, we find that the anisotropy in the loss of GO films dominates the polarization selectivity of these devices. These results highlight the strong potential of 2D GO films for realizing high-performance polarization selective devices in Si photonic platform.

Domestic crime, conflict, and instability pose a significant threat to many contemporary governments. These challenges have proven to be particularly acute within modern-day Mexico. While there have been significant developments in predicting intrastate armed and electoral conflict in various contemporary settings, such efforts have thus far been limited in their use of spatial as well as temporal correlations, as well as in the features they have consid- ered. Machine learning, especially deep learning, has been proven to be highly effective in predicting future conflicts using word embeddings in Convolutional Neural Networks (CNN) but lacks the spatial structure and, due to the black box nature, cannot explain the importance of predictors. We develop a novel methodology using machine learning that can accurately classify future anti-government violence in Mexico. We further demonstrate that our approach can identify important leading predictors of such violence. This can help policymakers make informed decisions and can also help governments and NGOs better allocate security and humanitarian resources, which could prove beneficial in tackling this problem. Using a variety of political event aggregations from the ICEWS database alongside other textual and demographic features, we trained various classical machine learning algorithms, including but not limited to Logistic Regression, Random Forest, XGBoost, and a Voting classifier. We considered a mix of CNN + Long Short Term Memory (LSTM) networks to decode the spatial and temporal relationship in the data. The performance of all the black box deep learning models was not at par with the classical machine learning models. We also evaluated the temporal relationships in the data to identify important predictors that fuel anti-government violence along with their directions using Shapley additive values. The voting classifier, utilizing a subset of features derived from LASSO across 100 simulations, consistently surpasses alternative models in performance and demonstrates efficacy in accu- rately classifying future anti-government conflicts. Notably, Random Forest feature importance indicates that some features, including but not limited to homicides, accidents, material conflicts, and positive worded citizen information sentiments emerge as pivotal predictors in the classification of anti-government conflicts. Finally, we conclude the research by analysing the spatial structure of the data using Moran’s I index extended version for spatiotemporal data to identify the global spatial dependency and local clusters followed by modelling the data spatially and evaluating the same using Gaussian Process Boost(GPBoost). The global spatial autocorrelation is minimal, characterized by local- ized conflicts cluster within the region. Furthermore, in Phase 3, the Voting Classifier method demonstrates superior performance over GPBoost, leading to the inference that no substantial spatial dependency exists among the various locations.

This paper presents the perspective that universe is relative. The universe, which changes according to the traveler’s proper time, is dynamic. While the universe generally expands, it could also contract if traveler accelerates sufficiently. The Hubble parameter merely represents that change. If the Hubble parameter is dependent on the proper time, the measurement can only be uncertain. Identifying the factors that influence the proper time could potentially lead to a more accurate measurement of the universe’s age, and it could also offer insights into the state of the early universe and the causes of the accelerated expansion observed in the current epoch.

In recent years, the treatment of locally-advanced rectal cancer (LARC) has been spotlighted in a number of landmark, practice-changing trials, heralding in the age of so-termed “total neoadjuvant therapy” (TNT). However, the lack of a common control arm, standard inclusion criteria, or, indeed, definition of TNT necessitates further study in this field, particularly using real-world data. We conducted a retrospective analysis of all patients treated for LARC at a single Canadian academic cancer centre between July 1st 2019 and July 14th 2022. This includes the June 2020 incorporation of TNT. 290 patients were included in the final analysis, and 124 variables were collected on each patient, including demographics, treatment type, adverse events, response to treatment, surgery versus watchful waiting and survival. Our findings demonstrate that both TNT and non-TNT regimens are highly toxic, with regards to both overall toxicity and grade 2+ adverse effects. 62 (96.9%) of patients on TNT experienced toxicities, compared to 186 (82.3%) of the non-TNT patients. Grade 2+ toxicities were 46 (71.9%) and 143 (63.3%), respectively. TNT, however, was associated with improved rates of complete response, compared to non-TNT treatment regimens (44% vs 24%). These findings suggest that TNT harbours both benefit and risk in a real-world population, and both of these aspects should be considered when deciding on a treatment approach for an individual patient. More work in the area is needed to determine longer term survival, as well as impact of surgery versus organ preservation approach on patient outcomes.

The critical role of manufacturing operations in enhancing the performance of Small and Medium Enterprises (SMEs) has become increasingly evident in recent years. This systematic review examines how manufacturing operations influence the performance of SMEs, analysing findings from 69 diverse research papers published between 2014 and 2024. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, the review focuses on key operational strategies, including lean manufacturing and advanced manufacturing technologies, assessing their effectiveness in improving business outcomes such as efficiency, productivity, and financial performance. The methodology included a thorough review of the research methods used in the studies, identifying potential biases, gaps, and highlighting the need for diverse approaches. While manufacturing operations have led to improved productivity and increased efficiency for many SMEs, challenges such as limited resources, lack of technical expertise, and resistance to change remain prevalent. Notably, a reporting bias was observed, with 48% of the literature composed of quantitative studies, 30% being mixed-method studies, and only 20% and 1% representing qualitative and exploratory studies, respectively. This imbalance suggests an overemphasis on quantitative methods, limiting the range of ideas and understanding available. Key strategies such as lean manufacturing and advanced technologies were shown to enhance productivity by 15% to 25% in SMEs. By adopting a broad approach, this review ensures that the findings are applicable across various sectors and geographies, offering valuable insights into best practices and challenges across diverse economic contexts. The broad scope also allows for the identification of under-researched areas, fostering a more comprehensive understanding of how manufacturing operations contribute to SME success. The review provides a decision-making framework for business leaders and policy recommendations to foster SME growth in a competitive, globalized market.

A fundamental aspect in the evolution of Time-to-Digital Converters (TDCs) implemented within Field-Programmable Gate Arrays (FPGAs), given the increasing demand for detection channels, is the optimization of resource utilization. This study reviews the principal methodologies employed for implementing low-resource TDCs in FPGAs. It outlines the foundational architectures and interpolation techniques utilized to bolster TDC performances without unduly burdening resource consumption. Low-resource Tapped Delay Line, Vernier Ring Oscillator, and Multi-Phase Shift Counter TDCs, including the use of SerDes, are reviewed. Additionally, novel low-resource architectures are scrutinized, including Counter Gray Oscillator TDCs and interpolation expansions using Voltage-Temperature-Consumption stable IODELAYS. Furthermore, the advantages and limitations of each approach are critically assessed, with particular emphasis on resolution, precision, non-linearities, and, especially, resource utilization. A comprehensive summary table encapsulating existing works on low-resource TDCs is provided, offering a comprehensive overview of the advancements in the field.

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly-large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remains elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

The automotive industry is continuously developing to meet the needs of users in terms of efficiency and convenience. The Thailand government has set a policy for Thailand to be a hub for the production of electric vehicles and key components in the region, with a target to produce electric and zero-emission vehicles by 2030. This article is an example of communication in an electric vehicle system. The CAN Bus system is a communication system in electric vehicles that can receive and send communication data via CAN-Hight/Low lines designed for vehicles. CAN Bus is a standard communication system supported by global organizations and used in modern automotive systems. The design of the communication system in electric vehicles uses MRS Developers Studio software to help write programs to receive and send data and prioritize the importance of the received data. The system consists of communication examples studied, such as pressing the start button, turning on/off the headlights, turning on/off the turn signal, turning on/off the brake light, turning on/off the emergency light, sending the horn signal, sending the signal to shift forward/backward, and tuning the motor gear system. From the communication examples mentioned, the communication will be a prototype transport set for small electric vehicles under the scope of the lithium battery energy storage system, NMC type, size 72 V 25 Ah, to test the use, efficiency, and stability in CAN Bus communication up to 1000 times.

In February of 2024, Dr. Jun Zhuang and Dr. Casey Kennington published a paper (Zhuang and Kennington, 2024) in which they classified large language model (LLM) survey papers into different taxonomies utilizing graph learning. In this paper, I evaluate the dataset they created and used and propose that in its current state, there is not enough samples to classify other survey papers into specific categories.

Apolipoprotein A (ApoA), an integral component of high-density lipoprotein (HDL) particles, plays a vital role in the transport and metabolism of lipids. It is implicated in both cardiovascular (CVD) and neurological diseases. In the context of CVD, ApoAs are pivotal in facilitating the reverse transport of cholesterol, mitigating inflammation, and preserving endothelial function. These char- acteristics highlight the crucial role of ApoA in averting the onset of CVDs. Moreover, ApoA has been implicated in the pathogenesis of several diseases, such as Alzheimer's disease (AD), Parkin- son's disease (PD), and multiple sclerosis (MS). Apart from its role in lipid metabolism, recent stud- ies have indicated the involvement of ApoA in neuroprotection, amyloid-beta clearance, and regu- lation of neuroinflammation. This paper addresses the research question: "How do different isoforms of Apolipoprotein A influence the development and progression of cardiovascular and neurological diseases, and what are the potential therapeutic implications of targeting ApoA in these conditions?" By providing a comprehensive review of current knowledge, this paper empha- sizes the importance of ApoA in understanding the intricate connections between cardiovascular and neurological health, suggesting that ApoA-targeted interventions may help treat diseases in both domains.

A microwave technique prepared a superabsorbent polymer (SAP) by grafting two hydrophilic monomers onto a polysaccharide substrate. The monomers used are acrylic acid (AA) or acrylamide (AM) to graft onto a pullulan substrate (PUL) to form PUL-g- AA (SAP1) and PUL-g- AM (SAP2), respectively. The monomers (AM/AA) graft together onto a PUL substrate to form PUL-g-(AM/AA) (SAP3). Grafting parameters such as grafting efficiency with percentage, conversion of monomer to polymer, gel content, water retention, water adsorption capacity, and swelling kinetics were determined. Additionally, the effect of environmental pH (2, 4, 7, 9, and 12) and sodium dodecylbenzene sulfonate (SDBS) surfactant was evaluated, where SDBS was added by 1,2,3,4 and 5 mM to form (SAP4 to SAP8). FTIR results show that AM grafted on PUL through an aliphatic C-N bond, while AA grafting occurred through a single C-C bond. The grafting efficiency with AM is higher than with AA, as well as their gel contents. Water absorbance capacity increased with grafting of AA or AM separately, and water retention was enhanced. The highest absorbent capacity, water retention, gel content, and grafting parameters values were obtained with 3 mM SDBS content and pH7. The swelling kinetics showed that the increases in the theoretical and experimental swelling equilibriums were 72 % and 82%, respectively, at SAP6 compared to the values of these parameters in SAP3. The water absorption capacity of the hydrogel increases with increasing pH to 7 and then gradually decreases. XRD improves the crystallinity and crystalline size of the hydrogel after grafting polymerization for AM/AA into PUL, in addition to enhancing thermal stability. On the contrary, FE-SEM demonstrated that SDBS improves the porosity and pore size of the hydrogel surface in SAP6.

In many countries, increasing concern for animal welfare is driving retailer commitments and government legislation that aim to improve the lives of farmed fish. One aspect of fish welfare involves stunning fish prior to slaughter. The feasibility of stunning depends on the species of fish and physical farm characteristics. In this article, we provide an overview of stunning before slaughter in European sea bass and sea bream aquaculture, one of the largest finfish farming industries in the developed world that does not yet stun most of its production. Sea bass and sea bream stunning necessitates the use of electrical stunning equipment aboard harvest vessels, often a significant distance from the shoreline; this presents an interesting engineering and policy challenge. Together, Türkiye, Greece, Spain, and Italy produced over 400,000 t of sea bass and sea bream in 2020. In Türkiye and Greece, farms are numerous and located very close to the shoreline. In Spain and Italy, farms are few and located far from the shoreline. The highest average production is found in farms from Türkiye (1,000 t) and Spain (1,300 t, and lower average production is found in Greece (300 t) and Italy (350 t). Producer progress towards the installation of electrical stunning appears comparatively well-developed for Türkiye, Spain, and Greece, though we emphasise that producers and other stakeholders require continued support to realise this opportunity. Producers in Italy appear slower to make progress on this aspect of animal welfare and may require additional support.

This paper shows the firsts results of a methodological approach in which Remote Sensing technologies (Satellite imagery and LiDAR) combined with Least Cost Path algorithm on GIS are being tested like tools to overcome locally-based interpretations about populational patterns and communication routes during Flavian municipality in the Comarca de El Condado region. The identification of fourteen hypothetical communication routes between already known archaeological sites thanks to a recent archaeological prospection, and the confirmation of three sections of them and a new archaeological site demonstrate that the combined use of the aforementioned technics has a very useful to delve more deeply, more widely and at a variety of different scales into the relation between the twelve known/selected Early Roman Empire sites and the surrounding landscape in the right bank of Guadalén River. It is expected that, in next phases, this methodological approach will allow us to go deeper in analysing and understanding spatial distribution, exploitation, and interrelation between different Early Roman Empire sites, helping us to fill the aforementioned gaps in our understanding of the archaeological continuum in the region reducing time and costs.

The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 2 m from other persons to avoid the spread of COVID-19. The exposure to the bioaerosol can result in the deposition of the pathogen in the respiratory tract of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic diameter (size) of particles in carrying RNA copies of the novel coronavirus. A SARS-CoV-2 carrier person talking, sneezing, or coughing at distance of 2 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far from the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.

We investigate the physics of a medium-size quantum particle' gases, of the order of hundreds or thousands of fermions/bosons (far below the thermodynamic limit $N \, \rightarrow \, 10^{24}$). Appeal to microcanonical ensemble becomes then unavoidable. The so-called statistical complexity is our protagonist. Interesting facts are uncovered, both for fermions and bosons, yielded by statistical quantifiers.

Two Iron Age settlements, Tuzusai and Taldy Bulak 2 (ca. 500 BCE to 1 CE), located in Southeastern Kazakhstan on the Talgar alluvial fan north of the Tian Shan range, have yielded a small collection of bone, antler/horn, bronze, and stone artifacts with affinity to nomadic art of the first millennium BCE. Both settlements date within the period of late Saka culture. Two pieces have decorative ornamentations with zoomorphic imagery: a small carved fragment of a with carved images of a wing and an ear and a perforated bone disk with the carving of three birds’ heads. The other artifacts include objects associated with Saka weaponry or nomadic economy such as the two antler/horn psalia (cheek pieces) and a bronze amulet. A carnelian bead will also be described as an imported object. These special finds are found on the occupation floors of mud brick houses and pit houses of settlements, not in grave or burial contexts. The objects are placed in stratigraphic sequence in the settlement sites. Then the method for placing these objects within the chronological framework of “animal-style art” is through comparisons with similar objects found throughout Eurasia—a method used in Soviet and Post-Soviet archaeology. The results show that functional and stylistic elements of the six objects indicate that the Talgar settlements were part of a larger world-system of trade and communication along the early Silk Route(s).

While the link between Sensory-processing sensitivity (SPS) and internalizing symptoms has been well-established, a link to externalizing problems is still to be explored. This study aimed to further examine the relation between SPS and behavioral problems by testing the potential mediating roles of trait emotional intelligence (TEI) and decision-making styles. Pathway analyses were conducted on data from 268 community sample participants (Mage= 25.81, SD=2.41, 61.2% females). Results indicated gender differences in the pathway level outcomes of SPS, as well as potential partial mediators in men and women. SPS both directly and via the mediating effects of well-being factor (TEI) and avoidant decision-making influenced depression, regardless of gender. Direct effects on aggression were, however, obtained only in the male sample. Indirect effects of SPS on aggression were found in spontaneous decision-making for men, and in self-control and sociability factors of TEI for women. Directions for future research were discussed. sensory-processing sensitivity, depression, aggression, emotional intelligence, decision-making style, gender differences

Background and Aim: Patients with Type 2-diabetes condition tend to have multiple medications in various dosage which leads to complex medication regimens. Complexity of regimen results in poor adherence, uncontrolled glycemic value and treatment failure. The research aimed to investigate medication regimen complexity index, medication adherence, and impact of medication regimen complexity on glycemic control and medication adherence.Materials and Methods: A Crossectional Study methods was conducted at Bheri Hospital Nepalgunj, among 145 Diabetes patients. Medication adherence was assessed by using a General Medication Adherence Scale (GMAS Nep-Tool). Medication regimen complexity was assessed by using a Medication Regimen Complexity Index (MRCI) tool. Chi-square test, One-way ANOVA, Paired t-test, and binary logistic regression were used for inferential statistics. Results: This study shows that most of the participants were female and aged group 50-59 years. Hypertension was the most common comorbidity, followed by hypothyroidism. The majority of participants exhibited partial adherence 90 (62.1%) to their medication regimen. It was seen that medications prescribed for diabetes were more complex than non-diabetes medications (Mean±SD MRCI: 8.28±3.155 vs. 4.57±2.107). The negative correlation was seen with diabetes MRCI and medication adherence (r=-0.090). There was statistically significant association between diabetes MRCI and glycemic control, (p<0.05). Binary logistic regression revealed that females had lower odds of high MRCI compared to males ( multivariate p-value: 0.014, AOR: 0.403, 95% CI: 0.195-0.832), while sedentary lifestyle showed high Diabetes MRCI (COR: 4.709, 95% CI: 0.962-23.05) and abnormal BMI were associated with higher MRCI (binary p-value: 0.067, COR: 2.30, 95% CI: 0.942-5.65; multivariate p-value: 0.092, AOR: 2.323, 95% CI: 0.878-5.67). Conclusion: Diabetes medications are more complex, reducing adherence and worsening A1C outcomes. Simplifying regimens improves results, with MRCI being valuable for healthcare providers. The medication adherence and therapeutic outcomes can be improved by the improved by the involvement of clinical pharmacist using MRCI.

In recent years, there has been a significant demand for Instructional Design (ID) professionals due to the rise of remote work, increased reliance on digital learning solutions for professional development, and the integration of digital technologies in formal and informal learning spaces. However, practical and authentic personalized courses are unavailable for professionals who want to transition into the field. This study addresses the gaps in most of the available ID courses and details the design of an Instructional Design Skill-Strength Assessment System (IDSSAS) that evaluates gaps in users' skills and offers them courses and mentors to help them bridge them in preparation for work as an ID in the corporate space. Employing a User-Centered Design (UCD) approach, the system prioritizes personalization, real-world application, and practical skills that better position them to be more employable, a significant improvement over the mostly available traditional, theory-focused ID training programs. IDSSAS, which is integrable with any Learning Management System (LMS) or Learning Experience Platform (LXP), was developed with Storyline 360, and it offers personalized learning and feedback as well as provides users with the agency to choose a mentor that is best aligned with their area of interest. The design was grounded in Self-Determination Theory (SDT) and incorporates design features like a progress bar, feedback loop, challenges, social interaction, and agency to support students' motivation and promote Autonomy, Relatedness, and Competence. IDSSAS, in its manual and present automated form, has been successfully used to mentor some transitioning ID professionals globally who are now gainfully employed.

in this research, new setting is introduced for new SuperHyperNotion, namely, Neutrosophic SuperHyperStable. In this research article, there are some research segments for ``Neutrosophic SuperHyperStable'' about some researches on neutrosophic SuperHyperStable. With researches on the basic properties, the research article starts to make neutrosophic SuperHyperStable theory more understandable. Assume a neutrosophic SuperHyperGraph. Then a ``neutrosophic SuperHyperStable'' $\mathcal{I}_n(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum neutrosophic cardinality of a neutrosophic SuperHyperSet $S$ of neutrosophic SuperHyperVertices such that there's no neutrosophic SuperHyperVertex to have a neutrosophic SuperHyperEdge in common. A basic familiarity with SuperHyperGraph theory and neutrosophic SuperHyperGraph theory are proposed.

This study investigated how fashion is expressed on social media platforms from a media ecology perspective of sustainable digital space-time, as society evolves into a digital ecosystem. Media ecology concerns how the media environment transforms human experience and impacts society and culture. A theoretical review of media ecology was conducted, and the Instagram account of global fashion influencer Susanna Lau (@susiebubble) was analyzed as a case study. In total, 300 fashion-related images were collected out of 5,817 uploaded to Lau’s Instagram between May 2012 and June 2019. These were analyzed—alongside their titles, content, hashtags, and commentaries—for visual phenomena conveying everyday divisions between spatiality and temporality, public and private, real and virtual, and geography and culture, which demonstrate ambiguous boundaries. The analysis revealed that the images reflect nuances of digital time and space as they emerge in social media, and represent a nonboundary of style across the binaries of work and leisure, public and private, real and virtual, and geography and culture—signifying a sustainable digital lifestyle. These findings illustrate how our changing daily lives are visualized through fashion on a sustainable digital platform, and suggest ongoing research into the practical impact of technological advances on fashion.

A novel concept of ion separation Anisotropic Diffusion Mobility Analyser (ADMA) with Individual Ion Counter (IIC) was shown by numerical modelling to be able to separate ions with high resolution and ultra-high sensitivity. An ADMA-IIC device has been developed and tested at sheath flow rates below 40 l/min with a number of chemicals relevant to airport security and military applications. The resolving power of the ADMA was observed to be in the range of 40 to 80. These data were close to the resolution obtained in numerical modelling predictions. It is greater than or comparable with the RP of currently available on-the-market devices for airport security and other applications. It was also confirmed that the ADMA technology enables very fast detection of analytes, at least 100 times faster than ion mobility spectrometers. It was shown that Brownian diffusion can be controlled and even overpowered by generating highly anisotropic diffusion in the ADMA device. The ultimate sensitivity of single-ion detection below the ppq range has been demonstrated.

The fractal dimension of is identified in this paper. More importantly, the undertaken research has shown how affects the Koch snowflake . The study has demonstrated the existence of negative values of (Koch snowflake), which connects to a considerable number of extremely intriguing mathematical and physical research areas. The information-theoretic impact on the Sierpiniski Gasket dimension , which corresponds to , was treated in a more fundamental way. Notably, the credibility of this current study adds to the existing kThe fractal dimension of is identified in this paper. More importantly, the undertaken research has shown how affects the Koch snowflake . The study has demonstrated the existence of negative values of (Koch snowflake), which connects to a considerable number of extremely intriguing mathematical and physical research areas. The information-theoretic impact on the Sierpiniski Gasket dimension , which corresponds to , was treated in a more fundamental way. Notably, the credibility of this current study adds to the existing knowledge for the information- theoretic fractal dimensions. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The investigation of the threshold theorems for and in terms of the triad is part of the next study phase. Additionally, investigating the newly obtained 's corresponding arbitrary Sierpinski Gasket for the first time.applicative note, this paper offers some potential applications of fractal dimension to smart cities. The investigation of the threshold theorems for and in terms of the triad is part of the next study phase. Additionally, investigating the newly obtained 's corresponding arbitrary Sierpinski Gasket for the first time.

Analysis of complex DNA mixtures is limited by the selected genetic markers characterized and assay technology. Small panels of short tandem repeats (STRs) are the current standards in most countries. Extension of STRs with hundreds of single nucleotide polymorphisms (SNPs) is now commercially available. The current set of extension SNPs focus on phenotypic and biogeographic ancestry informative SNPs. Larger panels with thousands of SNPs have been developed that can identify up to 10 contributors to forensic DNA samples. Herein, multiple sets of SNPs were selected with the focus of increasing the upper limit of detectable contributors. Larger SNP panel sets with lower minor allele frequency (MAF) alleles can detect large numbers of contributors to in silico mixtures of randomly selected profiles from the 1,000 Genomes project. These results provide a path to enable characterization of complex DNA mixtures that are currently impossible to analyse.

In today’s business landscape, customer retention has become a critical factor for sustainable growth. Many companies continue to focus on acquisition, which leads to high costs and constant customer turnover. This article highlights the importance of retention, proposing a shift in focus toward loyalty as the key to maximizing customer lifetime value (LTV). Improving retention not only increases LTV but also reduces acquisition costs, enhances virality, and provides financial stability. This paper introduces a scientific approach that allows companies to identify the underlying causes of low retention through observation, hypothesis formulation, and controlled experimentation. Using tools such as data analysis and A/B testing, companies can iteratively optimize their retention strategy, adjusting interventions in real-time based on the results obtained. Continuous experimentation emerges as an indispensable tool for navigating market complexity, enabling organizations to learn and adapt quickly. This data-driven approach not only improves retention but also drives long-term growth by building strong relationships with customers. In an increasingly competitive environment, companies that prioritize retention and experimentation are better positioned to achieve resilient and profitable growth.

This study discusses the application of reinforcement learning (RL) in financial asset risk assessment, especially how to improve the ability of risk prediction and asset portfolio optimization through deep reinforcement learning (DRL) model. Traditional financial risk assessment methods are often unable to effectively cope with the dynamic changes and complexities of the financial market, but RL technology provides innovative solutions for modern financial risk management by means of real-time adjustment and adaptation mechanism. This paper experimentally verifies the advantages of DRL models in improving forecasting accuracy and risk management efficiency and discusses the potential impact of AI technology in the financial sector. The findings show that despite challenges such as data quality and model interpretation, the application of AI technology provides financial institutions with more precise and flexible risk management tools, driving further development of fintech.

Music has been proposed for a long time as a treatment for mental disorders. However, some special types of music or stimulating sounds might induce negative emotions. Herein, 8-week-old male mice were exposed to two specific genres of music, hip-hop (HH) and heavy metal (HM), and construction noise (CN), and a series of behavioral experiments were performed to evaluate the impact of these music or sounds on the emotion of mice. The experiment lasted 1 week in which 8-week-old male mice were used as animal models. We found that long term exposure HM, HH, and CN induced depressive symptoms with a decrease in dopamine receptor 1 and BDNF in the mixture of hippocampus and frontal cortex of mice. Our results have highly addressed that certain special types of sound or music might induce negative emotions and loss of dopaminergic neurons in mice, and it is necessary to intervene in adolescences who are exposed to these music or sounds for a long time.

A presentation is provided of a structural approach for the concurrent teaching of introductory propositional calculus and set theory. The existence of isomorphism is shown between each law (or tautology) of propositional calculus and the form of a corresponding set which is equal to the universal set U considered.

Coral reefs are one of the most productive yet vulnerable ecosystems on Earth. An important step in understanding the functioning of coral communities is studying the environmental impact on the state of reefs. The present study aimed to assess the impacts of the water temperature, precipitation, wave action and population density on the seasonal bleaching, partial and complete mortality of shallow-water branching corals of Pocillopora verrucosa species complex. The present study was conducted at the Dam Bay research station (Nha Trang Bay) from 26 April 2020 to 2 April 2021. Throughout the study the percentage of bleached coral colonies varied from 1 to 41.5% with two peaks, in autumn (October) and spring (April). Rates of the development of partial mortality varied from 0 to 10%, with a pronounced peak in December. At the end of the experiment, the percentage of coral colonies suffering from partial mortality reached 47%. Only 4,5% of experimental colonies died by the end of the study. Analysis revealed that water temperature and partial mortality are the drivers of bleaching, while wave action, temperature and bleaching are the factors with a significant impact on partial mortality. In the present study, the main cause of coral death was the development of algal fouling at the sites of colony lesions, which gradually spread over the entire surface of the colony. We showed also that the impact of individual stress on mortality prevailed over the impact of seasonal bleaching and partial mortality events.

Cotton seeds as the main by-product of cotton are not only an important raw material for edible oil and feed but also a source of biofuel. The quality of cotton seeds directly affects cotton planting and is closely related to the yield and fiber quality. However, the molecular mechanism governing cotton seed size remains largely unexplored. This study investigates the regulatory mechanisms of cotton seed size by focusing on two cotton genotypes, N10 and N12, which exhibit notable phenotypic variations across multiple environments. Developing seeds were sampled at various stages (5, 20, 30, and 35 DAP) and subjected to RNA-seq. The temporal pattern clustering and WGCNA on differentially expressed genes identified 413 candidate genes, including these related to sugar metabolism that were significantly enriched in transcriptional regulation. A genetic transformation experiment indicated that the overexpression of the GhUXS5 gene encoding UDP-glucuronate decarboxylase 5 significantly increased seed size, suggesting an important role of GhUXS5 in regulating cotton seed size. This discovery provides crucial insights into the molecular mechanisms controlling cotton seed size, helping to unravel the complex regulatory network and offering new strategies and targets for cotton breeding to enhance the economic value of cotton seeds and overall cotton yield.

The accurate assessment of wound size is a critical step in advanced wound care management. This study aims to introduce and validate a Light Detection and Ranging (LiDAR) technique for measuring wound size. Twenty-eight wounds treated from December 2022 to April 2023 at the Chunganam National University Hospital were analyzed. All wounds were measured using three techniques; conventional ruler methods, the LiDAR technique, and ImageJ analysis. Correlation analysis, linear regression, and Bland-Altman plot analysis were conducted to validate the accuracy of the newly introduced method. The measurement results (Mean ± Standard deviation) obtained using the Ruler method, LiDAR technique, and ImageJ analysis were 112.99 ± 110.07 cm², 73.59 ± 72.97 cm², and 74.29 ± 72.15 cm², respectively. The Pearson correlation coefficient was higher in the LiDAR application (0.995) than the conventional ruler methods (Mean difference; -5.0000 cm2), as was the degree of agreement (Mean difference; 38.6933 cm2). Wound size measurement using LiDAR is a simple and reliable method that allows practitioners to conveniently assess wounds with a flattened and irregular shape. However, non-flattened wounds cannot be assessed owing to the technical limitations of LiDAR.

Although some alternative metrics have been proposed in classical gravity, the singularity problem remains unresolved perfectly. To satisfy the super-gravitational requirement of a black hole without singularities, we propose some possible finite-size structure to avoid the confused one. In this research, the degenerate Fermi electron gas is first used to reveal that the Fermi electron gas cannot shrink to a point regardless of how much energy it obtains; therefore, the singularity existing at the center becomes very unreasonable. To avoid these problems, a finite-size nucleus of the black hole is proposed and explained by the behaviors of the Fermi electron gas and Fermi neutron gas for this finite-size nuclear model. We construct the Kerr-Newman black hole by using a non-rotating but charged finite-size nucleus, a compact-like star, which is surrounded by counter-rotating and corotating electrons. Based on this model, the super-gravity the same as the one from a black hole is presented, and the speed of light observed at far-away places can be nonzero at the event horizon.

The Finite size Lyapunov exponent (FSLE) has been used extensively since the late 1990’s to diagnose turbulent regimes from Lagrangian experiments and to detect Lagrangian coherent structures in geophysical flows and two-dimensional turbulence. Historically, the FSLE was defined in terms of its computational method rather than via a mathematical formulation, and the behavior of the FSLE in the turbulent inertial ranges is based primarily on scaling arguments. Here we propose an exact definition of the FSLE based on conditional averaging of the finite amplitude growth rate (FAGR) of the particle pair separation. With this new definition, we show that the FSLE is a close proxy for the inverse structural time, a concept introduced a decade before the FSLE. The (in)dependence of the FSLE on initial conditions is also discussed, as well as the links between the FAGR and other relevant Lagrangian metrics, such as the finite time Lyapunov exponent and the second order velocity structure function.

Additive manufacturing (AM) is today’s buzzword—and not only in commercial production. One of the AM techniques produces 3D objects with complex geometry using a laser beam. The relationship between the morphology of individual powder particles and the printing process has not been adequately documented yet. This article presents a detailed microscopic analysis of virgin and reused powder particles of maraging steel. Metallographic observation was performed using a scanning electron microscope (SEM). Detailed analyses of individual particles were carried out using SEM with a focused ion beam (FIB) milling capability. Analyses of elemental distribution and phase distribution were performed using EDS and EBSD, respectively. The findings have led to a better understanding and prediction of defects in additive-manufactured products.

There are no studies that quantitatively compare life histories among scorpion species. Statistical procedures applied to 94 scorpion species indicate that those with larger bodies do not necessarily have larger litters or longer life cycles, opposite to some theoretical predictions.

In this paper we show that the Schwarzschild radius can be extracted easily from any gravitationally-linked phenomena without having knowledge of the Newton gravitational constant or the mass size of the gravitational object. Further, the Schwarzschild radius can be used to predict any gravity phenomena accurately, again without knowledge of the Newton gravitational constant and also without knowledge of the size of the mass, although this may seem surprising at first. Hidden within the Schwarzschild radius are the mass of the gravitational object, the Planck mass (their relative mass), and the Planck length. We do not claim to have all the answers, but this seems to indicate that gravity is quantized, even at a cosmological scale, and this quantization is directly linked to the Planck units. This also supports our view that the Newton gravitational constant is a universal composite constant of the form $G=\frac{l_p^2{c}^3}{\hslash }$ , rather than relying on the Planck units as a function of G. This does not mean that Newton’s gravitational constant is not a universal constant, but that it is instead a composite universal constant that depends on the Planck length, the speed of light, and the Planck constant. Further, $\frac{G\times 1\hspace{0.17em}\mathrm{weight}\hspace{0.17em}\mathrm{unit}}{c^2}=\frac{G}{c^2}$ is the Schwarzschild radius off one weight unit. So G is only needed when we want to use gravity to find the weight of an object, such as weighing the Earth. This is, to our knowledge, the first paper that shows how a long series of major gravity predictions and measurements can be completed without any knowledge of the mass size of the object, or Newton’s gravitational constant. As a minimum we think it provides an interesting new angle for evaluating existing gravity theories, and it may even give us a small hint on how to combine quantum gravity with Newton and Einstein gravity.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

The objective of this study was to create yogurts enriched with freeze-dried probiotic culture and freeze-dried fermented black chokeberry juice, in conjunction with a commercial starter culture. This approach was adopted to boost functionality and optimize the nutritional content of the yogurt. The study specifically investigated the impact of supplements, which included (i) freeze-dried probiotic culture Lactobacillus plantarum ATCC 14917 and (ii) freeze-dried fermented chokeberry juice Lactobacillus plantarum ATCC 14917, as adjuncts in different formulations of yogurt. These formulations were then compared with commercially produced yogurt. All the products exhibited favorable physicochemical properties, and the probiotic strain consistently maintained levels exceeding 7 log cfu/g throughout the entire storage period. The highest lactic acid production was observed in yogurts produced with the proposed adjuncts (1.44 g/100 g yogurt at the 28th days of storage). Levels of syneresis were observed in lower values in yogurt produced with freeze-dried fermented chokeberry juice. Yogurts prepared with the supplement derived from fermented juice displayed elevated total phenolic content and antioxidant capacity (25.74 µg GAE/g and 69.05 µmol TE/100g respectively). Moreover, sensory tests indicated an exceptional aroma and fruit flavor. The results demonstrate that the inclusion of dried probiotic-fermented chokeberry juice as an adjunct in yogurt production enhances both the antioxidant capacity and the growth of beneficial bacteria. Furthermore, the dried form of this product makes it a significant candidate for industrialization potential due to its stability and ease of application.

For a number of reasons, a curative treatment for most chronic diseases is still unrealized [2–4] and the incidence of many chronic diseases is rapidly increasing [5–9]. A new model is offered as a solution; that being the individualized diagnosis of homeostasis, leading to the correction of epimutations. Homeostasis diagnosis and epimutation correction, HDEC. Individuals with chronic diseases are increasingly being defined by their epimutation signatures [10,11]. Modern innovations in toxicogenomic studies are also becoming more accurate in their ability to identify the unique epigenetic signature of each toxin [12–14]. Hormesis studies (over 5,000) [15] suggest a universal principle, that a small dose is always a stimulant [16–18].These three facts present an opportunity; a method to diagnose and reverse chronic disease tendencies. This new model requires a paradigm shift in our understanding of disease origins: that dysfunctions in homeostasis [19,20] are the primary and deepest level of chronic disease causation. This is the level where the diagnosis needs to be made and where the corrections need to take place [21].

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combinations of factors/genes/proteins that might be affecting the pathway under certain conditions. In colorectal cancer (CRC) cells treated with ETC-1922159, many genes were found up and down regu- lated, individually. A recently developed search engine ranked combinations of AN- TXR cell adhesion molecule 2 (ANTXR2)-X (X, a particular gene/protein) at 2nd order level after drug administration. These rankings reveal which ANTXR2-X combinations might be working synergistically in CRC. If found true, oncologists can further test the combination of interest in wet lab and determine the mechanism of functioning be- tween the ANTXR2 and X. In this research work, we cover combinations of ANTXR2 with Collagen (COL), Integrin (ITG), Matrix metalloproteinases (MMP), WNT, TNF and Interleukin (IL) .