Keywords: environmental impacts of hotels; environmental management in lodging facilities; corporate sustainability.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

We previously reported nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes and tumors were harvested at 4-hour, 8-hour, 1-, 3-, 7-day. Additional studies were conducted over 3-month posttreatment intervals for the analysis of frequencies, death and functional markers of various immune cells in addition to suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promoted both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, likely explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state allowing cytotoxic T-cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, ligand binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through eco-pharmaco-economic analysis (EPEA). Results revealed the binding affinities of chemical disinfectants to viral proteins varied significantly (p

To understand dynamics in climate change, informing policy decisions and prompting timely action to mitigate its impact, this study provides a comprehensive analysis of the short-term trend of year-on-year CO2 emission changes across ten countries, considering a broad range of factors including socioeconomic, CO2-related industry, and education. This study uniquely goes beyond the common country-based analysis, offering a broader understanding of the interconnected impact of CO2 emissions across countries. Our preliminary regression analysis, using the ten most significant features, could only explain 66% of variations in the target. To capture emissions trend variation, we categorized countries by the change in CO2 emission volatility (high, moderate, low with upward or downward trends), assessed using standard deviation. We employed machine learning techniques, including feature importance analysis, Partial Dependence Plots (PDPs), sensitivity analysis, and Pearson and Canonical correlation analyses, to identify influential factors driving these short-term changes. The Decision Tree Classifier was the most accurate model, with an accuracy of 96%. It revealed population size, CO2 emissions from coal, the three-year average change in CO2 emissions, GDP, CO2 emissions from oil, education level (incomplete primary), and contribution to temperature rise as the most significant predictors, in order of importance. Furthermore, this study estimates the likelihood of a country transitioning to a higher emission category. Our findings provide valuable insights into the temporal dynamics of factors influencing CO2 emissions changes, contributing to global efforts to address climate change

An important issue concerning the inspection of the technical condition of electrical power components and systems is thermal imaging investigation. This paper presents how the thermograms obtained from these measurements should be interpreted correctly according different standards and how operators should react when a specific anomaly is detected. It is also a review article in which all currently applicable international standards are referred to. The motivation of the article relates to the fact that these standards seems to be too general and not cover all practical situations even though in many countries thermal imaging diagnostics of overhead lines or overhead outdoor and indoor power stations has been used for years on the basis of industry standards or good practices. The purpose of writing this article is precisely to encourage and provoke the global community of metrologists, scientists and engineers involved in thermographic measurements to discuss, strengthen efforts and establish relevant international standards for the interpretation of thermograms containing the relevant temperature anomalies.

Recent discoveries of potential ice particles and ice-cemented regolith on celestial bodies like the Moon and Mars have ushered in new opportunities for developing technologies to extract water, facilitating future space missions and activities on these celestial surfaces. This study delves into the potential for water extraction from regolith through an experiment designed to test water recuperation from regolith simulant under varying gravitational conditions. The resultant water vapor extracted from the regolith is re-condensed on a substrate surface and collected in liquid form. Three types of substrates, hydrophobic, hydrophilic, and grooved, are explored. The system’s functionality was assessed during a parabolic flight campaign simulating three distinct gravity levels: microgravity, lunar gravity, and Martian gravity. Our findings reveal that the hydrophobic surface demonstrates the highest efficiency due to drop-wise condensation, and lower gravity levels result in increased water condensation on the substrates. This experiment aims to provide insights into in-situ water recovery, which is pivotal for establishing economically-sustainable water supplies for future missions.

In this research paper, we address the critical role of data security in the rapidly evolving FinTech sector. We explore the challenges and strategies for establishing robust data security systems, emphasizing the consequences of data breaches and common vulnerabilities. The paper highlights the efficacy of technologies like encryption, blockchain, and cloud security, supported by real-world case studies from leading FinTech companies. Additionally, we examine regulatory frameworks and standards essential for maintaining data security. Concluding with the proposal of an integrated security system model, the paper underscores the synergy between technological innovation, regulatory compliance, and proactive risk management in the FinTech industry

The Model-View-Controller (MVC) architecture, a cornerstone of modern software engineering, offers a robust framework for developing dynamic user interfaces. This paper conducts a broad analysis of MVC’s deployment across various sectors, emphasizing its critical role in technological advancement and market integration. By examining implementation strategies in web development, mobile applications, and enterprise solutions, the study illustrates how MVC enhances application manageability, promotes efficient code reuse, and facilitates parallel development. The paper explores the adoption of MVC principles within major technologies such as Java, .NET, and JavaScript frameworks, underlining its widespread acceptance. Additionally, the analysis covers the preferential use of MVC frameworks within diverse market sectors including technology enterprises, educational institutions, e-commerce, and financial services, which leverage MVC for superior data management and user experience. Emerging trends such as the shift towards the Model-View-ViewModel (MVVM) architecture and the integration of MVC with artificial intelligence and machine learning technologies are also discussed. This comprehensive review not only reaffirms MVC’s enduring relevance but also its adaptive evolution in response to emerging technological demands and market needs.

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

A novel five-surface phosphor-in-ceramic (FS-PiC) for high illumination and excellent color uniformity in larger-scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680°C to form a phosphor wafer. A sophisticated laser engraving was employed on the phosphor wafer to form a saddle-shaped large-scale FS-PiC LEDs. The performance of the FS-PiC LEDs exhibited the illumination of 401lm, average color temperature (CCT) of 5488K±110K, and color coordinates (CIE) of (0.3179±0.003, 0.3352±0.003). In contrast to convention single-surface phosphor-in-ceramic (SS-PiC) LEDs, the performance exhibited the illumination of 380lm, average CCT of 5830K±758K, and CIE of (0.3083±0.07, 0.3172±0.07). These indicated that the performance of the FS-PiC LEDs was higher than the SS-PiC LEDs for illumination, CCT, and CIE of 1.1, 7, and 23 times, respectively. Furthermore, the FS-PiC LEDs demonstrate lower lumen loss of 2% and less chromaticity shift of 5.4x10-3 under accelerated aging at 350°C for 1008 hours, owing to the high ceramic melting temperature of up to 510°C. In this study, the proposed FS-PiC larger-scale LEDs having excellent optical performance and high reliability may be the promising candidates to replace the convention phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

Background: Swept-source anterior segment optical coherence tomography (SS-AS- OCT) is a suitable examination for the vitreolenticular interface. Methods: In a prospective study using Anterion (Heidelberg Engineering, Heidelberg, Germany) 102 eyes of 102 patients were examined, in pupil dilation, preoperatively and 6 times over 1-year follow-up. Preoperatively anterior hyaloid membrane (AHM) visibility was determined with Imaging App with high reliability. Postoperatively capsular bag–AHM distance was measured on six points by using Metrics App. Results: The AHM was visible in 18.6% preoperatively and postoperatively as well (Group 1), 49% of the preoperatively adherent AHMs became visible (Group 2A), 32.4% remained attached (Group 2B). Group 1: the average deepest point first day was 782.5 ± 324.1 microns, and it significantly differed from the later follow-up values. Group 2A: the average deepest value was 184.1 ± 220.1 microns, and there was no statistically significant difference between the postoperative visit values. The difference between the groups was statistically significant at every location and at each time points. Conclusions: AS-SS-OCT can be used to check BS both preoperatively(with limitations) and postoperatively.

The successful 2020 launch and 2021 landing of the National Aeronautics and Space Administration’s (NASA) Perseverance Mars rover initiated the first phase of the NASA and European Space Agency (ESA) Mars Sample Return (MSR) campaign. The goal of the MSR campaign is to collect scientifically interesting samples from the Martian surface and return them to Earth for further study in terrestrial laboratories. The MSR campaign consists of three major spacecraft components to accomplish this objective: the Perseverance Mars rover, the Sample Retrieval Lander (SRL) and the Earth Return Orbiter (ERO). Onboard the ERO spacecraft is the Capture, Containment and Return System (CCRS). CCRS will capture, process and return to Earth the samples that have been collected after they are launched into Mars orbit by the Mars Ascent Vehicle (MAV), which is delivered to Mars onboard the SRL. To facilitate the processing of the orbiting sample (OS) by CCRS we have designed and developed a vision system to determine the OS capture orientation. The vision system is comprised of two cameras sensitive to the visible portion of the electromagnetic spectrum and two illumination modules constructed from broadband light emitting diodes (LED). Vision system laboratory tests and physics-based optical simulations predict CCRS ground processing will be able to correctly identify the OS post-capture orientation using only a single vision system image that is transmitted to Earth from Mars orbit.

This paper investigates the relationship between public spaces and quality of life (QoL) for older adults, aiming to identify knowledge gaps within the context of population ageing and urbanization. Recognizing the growing importance of sustainable urban development, the research explores how cities can foster active ageing and improve QoL through accessible and inclusive public spaces. A scoping literature review identifies five key QoL domains for older adults: autonomy, meaningful activities, positive social relationships, leisure opportunities, and health. The review highlights areas requiring further investigation, including the interplay between environmental design and social connections, intergenerational perspectives on public space liveliness, the influence of context on QoL and the built environment, and the value of qualitative research in this field. By contributing to the understanding of QoL in relation to public spaces through the lens of Person-Environment fit theory, this study aims to inform urban design, landscape architecture, and policymaking in the creation of age-friendly communities with inclusive public spaces.

This paper explores the application of machine learning (ML) algorithms in predicting trends in the fixed bond market, where traditional analytical methods have proven inadequate. Focusing on various ML techniques such as supervised and unsupervised learning, neural networks, and deep learning, the study evaluates their effectiveness in forecasting market movements. It details a series of experiments in which different ML models are rigorously trained and tested against historical bond market data. The findings reveal that models employing time series analysis and advanced deep learning show marked potential in accurately predicting bond market trends. Additionally, the paper delves into the challenges and limitations inherent in these ML approaches, including data requirements and the risk of model overfitting. Finally, it proposes directions for future research, emphasizing the integration of ML into broader financial market analysis.

Raru’s plants bark has long been used as traditional medicine in Batak’s tribe. Raru’s bark is derived from several trees that are usually used in a mixture in Batak traditional beverages. This bark is generally used as antidiabetic remedies. This study aims to combine the rarus’s bark extract and mocaf activated-carbon (MAC) in order to study antidiabetics in rats. The combination of raru’s bark extract and MAC were tested on male rats as of Sprague Dawley strain for testing antidiabetic bioactivity. The result showed that antidiabetic activity of raru’s extract and MAC exposed the antidiabetic level declines in rat’s blood. The various treatments of different concentration ratios of raru’s extract and MAC useful in the experiments showed that the levels of blood level reduction were slightly different (14-21%). The raru’s extract pure was observed more effective in decreasing the blood glucose level in rat’s blood, in comparison the positive control. The mixture of raru’s extract and MAC with 75:25 ratio is better than 50:50 ratio. The involvement of MAC in the alleged antidiabetic agent did little in improving the blood glucose level decrease in rat’s blood. Raru’s extract and MAC indicate its potential utilization as an antidiabetic agent.

Previous research has proven that one of the fundamental requirements for ensuring increased profitability and economic competitiveness of offshore-based projects is co-locating different technologies within the same marine space. This paper presents a number of techno-feasibility analyses for floating offshore technologies for the Maltese Islands, located in the Central Mediterranean Sea. The first part compares the feasibility of offshore-based solar photovoltaic prices with those onshore, taking into consideration Malta’s land prices. The second part considers the use of a novel floating breakwater design that integrates energy storage. The breakwater is used to create a sheltered water area in deep waters for a multi-use marine park. Different revenue streams for the floating break water are considered, including renting the sheltered marine space out to operators of floating solar farms, aquaculture cages and vessel berthing facilities, and the provision of energy storage services. It is found that the combined income from the multiple revenue streams is still insufficient to justify the investment and that financially support from Government is essential to render the floating breakwaters viable.

Crystallization of glass through conventional thermal annealing in a furnace is a well-understood process. However, crystallization by femtosecond (fs) laser brings another dimension to this process. The pulsed nature of the irradiation necessitates a reevaluation of parameters for optimal crystallization and to understand the particularities in the case of using fs laser. This includes adjusting the laser pulse energy, the repetition rate, and the writing speed to either initiate nucleation or achieve substantial crystal growth. Therefore, a key challenge to this work is to establish reliable calculations for understanding the relation of the size of the crystallized region with respect to an ongoing transition (e.g., solid-to-solid, liquid-to-solid), and accounting for the aforementioned laser parameters. In this context and based on previous work, we simulate a temperature distribution (in space and time) to model the thermal treatment at any point in the glass. By setting the condition that the temperatures are between the glass transition and melting temperature, we can deduce the crystallized region size to be compared with experimental observations. For that purpose, the knowledge of the beam width at the focal point and of the absorbed beam energy fraction are critical inputs that were extracted from experiments found in the literature. After that, management of the crystallization process and the width of the crystallization line can be achieved according to pulse energy e.g. crystallite size, and also the effect of the scanning speed can be understood. Among the main conclusions to highlight, we disclose the laser conditions that determine the extent of the crystallized area and deduce that it is never interesting to increase the pulse energy too much but rather the repetition rate for uniform crystallized line.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

Western countries are experiencing an increasing aging population, resulting in heightened disability and mobility issues. This trend is expected to escalate in the coming decades. Therefore, ensuring adequate accessibility in collective residential housing –where individuals spend much of their daily lives– is of paramount importance. This paper presents a case study focused on the accessibility of building entrances in collective residential housing in Southeast Spain, specifically in the Region of Murcia. In this region, 9.8% of the population has disabilities, and 15.75% were over 64 years old in 2020. The study began by compiling the relevant national and regional accessibility regulations for existing buildings. Subsequently, extensive fieldwork was conducted, analyzing 150 collective residential housing buildings. Based on this analysis, a set of recommendations to enhance accessibility was formulated for buildings not complying with the regulations. The results are presented and discussed in detail. The most frequent recommendation was the construction of accessible ramps, identified as the primary solution in over 40% of cases, either alone or in conjunction with other measures. In 54% of the cases, multiple interventions were necessary to achieve effective accessibility adaptation. The findings of this study could inform the development of public policies aimed at improving accessibility conditions in urban areas.

A spatial turn is increasingly being recognised across education, the humanities and social sciences to critique Western Cartesian assumptions treating space as either empty or a diametric opposition bringing dualistic splits between reason/emotion, and mind/body. Bacon’s vision of human subjugation of nature as a tool for human progress is examined as a diametric spatial projection, where humans are above and apart from nature, in a mirror image inverted symmetry of above/below hierarchy and side-by-side assumed separation as diametric space. Building on an interdisciplinary synthesis between an aspect of the structural anthropology of Lévi-Strauss, De Beauvoir’s othering and Bronfenbrenner’s social-ecological systems in psychology, allied with a Heideggerian critique of being as needing a mode of ‘being alongside the world’, a shift in experiential and conceptual space is proposed in this conceptual review article for education. This shift is towards a framework of concentric spatial systems of sustainability. Concentric relational spaces of assumed connection and relative openness and away from diametric spaces of splitting and closure have been developed recently for sustainability concerns regarding inclusion in education. This article goes further to interrogate systems of concentric relational space for belonging with and encountering the natural world for environmental sustainability.

Seeing atomic configuration of single organic nanoparticles at sub-Å spatial resolution by transmission electron microscopy has been so far prevented by the high sensitivity of soft matter to radiation damage. The difficulty is related to the need to irradiate the particle with a total dose of few electrons/Å2, not compatible with the electron beam density necessary to search the low-contrast nanoparticle, to control its drift, to finely adjust the electro-optical conditions and particle orientation, and to finally acquire an effective atomic resolution image. On the other hand, the capability to study individual pristine nanoparticles, such as proteins, active pharmaceutical ingredients, and polymers, with peculiar sensitivity to the variation of the local structure, defects, and strain, would provide advancements in many fields, including materials science, medicine, biology, and pharmacology. Here we report direct sub-ångström resolution imaging at room temperature of pristine unstained crystalline polymer-based nanoparticles. This result is obtained by combining low-dose in-line electron holography and phase-contrast imaging on state-of-the-art equipment, providing an effective tool for the quantitative sub-angstrom imaging of soft matter.

This paper introduces a novel architecture—bidirectional optical neural network (BONN)—for providing backward connections alongside forward connections in artificial neural networks (ANNs). BONN incorporates laser diodes and photodiodes and exploits the properties of Köhler illumination to establish optical channels for backward directions. Thus, it has bidirectional functionality that is crucial for algorithms such as the backpropagation algorithm. BONN has a scaling limit of 96 × 96 for input and output arrays, and a throughput of 8.5 × 1015 MAC/s. While BONN's throughput may rise with additional layers for continuous input, limitations emerge in the backpropagation algorithm as its throughput doesn't scale with layer count. Successful BONN-based implementation of the backpropagation algorithm requires the development of fast spatial light modulator to accommodate frequent data flow changes. A two-mirror-like BONN and its cascaded extension are alternatives for multilayer emulation, and they help save hardware space and increase the parallel throughput for inference. An investigation into the application of the clustering technique to BONN revealed its potential to help overcome scaling limits and to provide full interconnections for backward directions between doubled input and output ports. BONN's bidirectional nature holds promise for enhancing supervised learning in ANNs and increasing hardware compactness.

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

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

Background: The identification of novel therapeutic strategies for Ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-Hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with cyste-ine-dependent deubiquitinating enzymes (DUBs), thus affecting the ubiquitin-proteasome de-pendent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC cell lines, primary tumor cells cultured in 2D/3D and in a mouse xenograft model. We also propose an in-silico model of 2c interaction with DUBs. Finally, we tested the effect of 2c conju-gated to several linkers to generate 2c-derivatives usable for improved drug delivery. Results: 2c effectively impairs OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs pro-teasome activity and triggers apoptosis most likely by interacting with DUBs; we propose a mechanism for the interaction with a model DUB via an in-silico evaluation of the en-zyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcrip-tion factor E2F1. Finally, 2c activity is often retained after the conjugation with linkers. Conclu-sion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.

The Polyurethane (PU) mixture is a high−performance engineering material with different dynamic properties compared to a hot−mixed asphalt mixture (HMA). This paper analyzed whether the Kramers−Kronig (K−K) relation and thermo−rheological simple properties were applicable to the PU mixture. Based on the result discussion, the PU mixture exhibited thermo−rheological simple properties within the test conditions. The time−temperature superposition principle (TTSP) was applicable for the PU mixture to construct the dynamic modulus master curve using the standard logistic Sigmoidal (SLS) model, the generalized logistic sigmoidal (GLS) model, and the Havriliak−Negami (HN) model. The Hilbert integral transformed SLS and GLS models for the phase angle can accurately fit the measured phase angle data with newly fitted shift factors and predict the phase angle within the viscoelastic range. The Core−Core and black space diagrams both displayed single continuous smooth curves, which can be utilized to characterize the viscoelastic property of the PU mixture. The K−K relation is applicable for the PU mixture to obtain the phase angle master curve model, storage modulus, and loss modulus from the complex modulus test results. The phase angle of the PU mixture cannot be derived from the dynamic modulus data and currently needs to be derived from the laboratory measurement.

China is experiencing rapid urbanization. The focus on health issues has shifted from the treatment of diseases to passive or active prevention. Diseases caused by the deterioration of the urban environment, such as cardiovascular disease, diabetes, obesity and other chronic diseases and mental illness, have gradually become the main threat to public health. Studies have confirmed that urban green spaces (UGS) can help residents relieve mental stress, improve mood, reduce mental fatigue and restore attention, which has a positive effect on people's physical and mental health. In this study, the relationship between the quantity and quality factors of UGS and the physical and mental health of urban residents in Xihu District of Hangzhou is examined, and on this basis, UGS design strategies are proposed to promote the physical and mental health of residents. This study is of great significance for the future construction of UGS that are beneficial to the health of residents and the promotion of a healthy China and healthy city construction.

Museums are called to respond to contemporary challenges and contribute to the formation of more progressive societies. One of the major challenges of our time is climate change and museums could construct cocreated narratives around climate and implement targeted actions for the audiences through their sensorial and affective experiences. More specifically, Geology and Palaeontology museums are repositories of knowledge on geoheritage and geoconservation, recognized for their scientific, pedagogical, cultural and recreational values. The educational potential of geological and paleontological exhibits could be used in informal education activities regarding the climate emergency. Taking the above into consideration, this study focuses on both the creation and evaluation of an educational program for the Natural History Museum of Arsakeio Campus at Psychicko.

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

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

Time series forecasting has been a challenging area in the field of Artificial Intel-ligence. Various approaches such as linear Neural Networks, Recurrent Linear Neural Networks, Convolutional Neural Networks and recently Transformers have been attempted for the time series forecasting domain. Although, Trans-former-based architectures have been outstanding in the Natural Language Pro-cessing domain, especially in autoregressive language modeling, the initial at-tempts to use transformers in the time series arena have met with mixed success. One of the recent papers demonstrated that modeling the multi-variate time se-ries problem as independent channels on a transformer architecture produced lower mean square and mean absolute errors on benchmarks, however, another recent paper claimed that a simple linear neural network out-performs previous approaches including transformer-based designs. We investigate this paradox in detail comparing the linear Neural Network and Transformer based designs, provide insights to why a certain approach may be better for a particular type of problem. We also improve upon the recently proposed simple linear Neural Network based architecture by using dual pipelines with batch normalization and reversible instance normalization. Our enhanced architecture outperforms all existing architectures for time series forecasting on majority of the popular benchmarks.

We document for the first time epsilon waves on the electrocardiogram of a patient with Dravet syndrome (DS) who does not exhibit structural cardiac pathology. DS, a severe form of pediatric epilepsy, involves mutations in the SCN1A gene, which disrupt sodium ion flow and increase the risk of sudden unexpected death in epilepsy. The epsilon waves, typically associated with arrhythmogenic right ventricular dysplasia, may also suggest a link between neuronal and cardiac dysfunctions. In our case, the epsilon waves appear to originate from abnormalities in sodium channels rather than structural changes in the myocardium. This finding underscores the importance of assessing both neurological and cardiac manifestations in patients with severe epilepsy, opening new avenues for the research and treatment of these interactions in DS.

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

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

Retired Electric vehicles (EVs) batteries are reused in second life energy storage applications. However, the overall performance of repurposed energy storage system (ESS) is limited by the unevenness of individual batteries use in it. Therefore, battery grading is required for optimal performance of ESS. Electrochemical impedance spectroscopy (EIS) based evaluation of battery aging is a promising way to grade lithium-ion batteries. However, it is not practical to measure impedance of mass retired batteries due to high complexity and slowness. In this paper, a broadband multi-sine binary signal (MSBS) perturbation integrated with multichannel EIS system is presented to measure impedance spectra for high-speed aging evaluation of lithium-ion batteries or modules. The measurement speed is multi-times higher than conventional EIS with single-channel configuration. The broadband MSBS is validated with reference sinusoidal sweep perturbation and corresponding root-mean-square error (RMSE) analysis is performed. Moreover, the accuracy of the presented multichannel EIS system is validated by impedance spectra measurement of Samsung INR18650-29E batteries and comparing it with those measured with commercial EIS instrument. A chi-squared error under 0.641% is obtained for all 8-channels. Since the non-linearity of battery has significant impact on quality of impedance spectra. Therefore, Kronig-Kramer (KK) transform validation is also performed.

In recent years, the widespread introduction of bike-sharing systems in China has had a profound impact on the daily lives of Chinese citizens and the development of the urban transport system. This article attempts to analyse the impact of this phenomenon on sustainability. The gradual improvement of related monitoring measures has facilitated the maturation of the bike-sharing industry from the initial stage of uncontrolled growth to the current stage of standardised management. By tracing the global development of bike-sharing systems with a special focus on China, this study sheds light on the platformisation of bicycles and its multiple impacts on technical, environmental, cultural, economic and social sustainability. Furthermore, the study provides a comprehensive analysis of the transformation of bicycles in China and highlights the diverse impacts of platform-based bike sharing on various facets of Chinese society. The development of different bike-sharing systems in China is a unique and crucial case to interpret the current situation of bike-sharing and imagine future scenarios. In contrast to the prevailing and uniform approach derived from the experiences of Northern European countries, the massive and widespread experimentation with different bike-sharing schemes in China reveals not only potentials and aspects of sustainability, innovation and urban and social regeneration, but also some hidden shadows similar to those in small-scale contexts such as Northern Europe. Furthermore, the study emphasises the crucial role of sustainable development principles in addressing urban challenges specific to China.

The paper primarily demonstrates that the three internal triangles formed by connecting any point on a midsegment with the vertices of a generic triangle satisfy the geometric Proof of the Pythagorean theorem in Euclidean geometry. Moreover, this study elucidates the Pythagorean relationships inherent within three-dimensional geometric constructs resulting from the arrangement of three-dimensional spatial triangles. This geometric relationship, akin to a generalized extension of the Pythagorean theorem, unveils a unique spatial region characterized by this harmonious area interrelation among triangles.

This article begins with exploring fundamental limits in the universe. It examines key principles, such as the uniformity of physical laws and Energy conservation, that lead to maximum speed, locality, and maximum density. These universal limits govern physical phenomena, leading to very interesting results.I demonstrate that quarks and leptons comprise smaller entities named "Quantum Black Holes." These Quantum black holes are relativistically rotating miniature charged black holes consisting of a single core at the highest possible density. Quantum black holes are the only structures small enough in space-time capable of keeping all charges quantized (including gravitational charges.)By the end of the article, I prove that Quantum black holes explain the deficiencies of SM. They facilitate explanations of quantized gravity, the nature of Luminous and dark Matter, establishing the Mass, size, and (quantized) charges quantities of elementary particles, the nature of neutrino oscillations, and more. Elementary particles release their Energy outward, altering the curvature of nearby space-time and providing new insights into the nature of space-time curvature change. With this understanding, we can characterize movements and processes in local space-time using five sets of equations simultaneously: four representing the four charge types and one representing Dark Matter.

Despite the advances in stent design, coating drugs, polymers, the use of intravascular imaging, special devices (such as intravascular lithotripsy, ultra-high-pressure non-compliant balloons, and drug-coated balloons), and improved operator skills and techniques, the problem of in-stent restenosis (ISR) and stent thrombosis (ST) remains a challenge for interventional cardiologists. Atherosclerotic lesions, ISR, and ST, are systemic metabolic chronic inflammatory illnesses with a local manifestation in the coronary vessels. Therefore, we propose managing these systemic illnesses systemically through plant-based diet (PBD) intervention. We explain how PBD intervention can help mitigate atherosclerosis, ISR, and ST. Thus, PBD intervention can overcome biological and epigenetic problems in managing ISR and ST similarly to reversing atherosclerosis. Our team is pioneering the implementation of PBD for cardiology patients who have undergone coronary intervention. So far, the results have been very promising. We hope that in the future, many research studies will be performed to investigate further the role of PBD in decreasing the incidence of ISR and ST.

This paper is devoted to the study of multi-dimensional integral transform with Fox H-function in the kernel in weighted spaces integrable functions in the domain R+n with positive coordinates. Mapping properties such as the boundedness, the range, the representations of the considered transformation are established.

Differences between the quantum mechanical and relativistic concepts of time observed in GPS satellites are accounted for by applying the equivalence principle to the transitioning electron of an atomic clock. It allows a differential equation of motion to be derived for the electron in the Minkowski space between electron shells. Using Hamilton’s principle we transform the differential equation relativistically into an integral equation of motion, the time integral of a Lagrangian. This newly derived equation accounts for the abstract mathematics of the more familiar non-relativistic model by means of a physical interpretation. Abstract rotations in Hilbert space are replaced by the rotations of real particle field geometries in Minkowski space. Because the properties of energy are universal the same equations are then used to describe the field geometry of galaxies despite vast differences in lifetime. They reveal a symmetry between the electromagnetic fields of atoms and the gravitational fields of galaxies due to similarities in the exchange of energy by radial and transverse fields. Our analysis reveals that the conjugate variables energy and time permit differences between atomic and galactic structure to be compared in a more intuitive way than by means of the differential equations of motion which use the conjugate variables position and momentum.

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

Input noise causes inescapable bias to the weight vectors of the adaptive filters during the adaptation processes. Moreover, the impulse noise at the output of the unknown systems can prevent bias compensation from converging. This paper presents a robust bias compensation method for a sparse normalized quasi-Newton least-mean (BC-SNQNLM) adaptive filtering algorithm to address this issue. We have mathematically derived the biased-compensation terms in an impulse noisy environment. Inspired by the convex combination of adaptive filters' step sizes, we propose a novel variable-mixing-norm method to accelerate the convergence for our BC-SNQNLM algorithm, which is referred to as BC-SNQNLM-VMN. Simulation results confirm that the proposed method significantly outperforms other comparative works regarding normalized mean-squared deviation (NMSD) in the steady state.

Amid escalating urbanization, devising rational commercial space layouts is a critical challenge. Leveraging machine learning, this study uses a Back-propagation (BP) neural network to optimize commercial spaces in Weinan City's central urban area. The results indicate an increased number of commercial facilities with a trend of multi-centered agglomeration and outward expansion. Based on these findings, we propose a strategic framework for rational commercial space development emphasizing aggregation centers, development axes, and spatial guidelines. This strategy provides valuable insights for urban planners in small and medium-sized cities in the Yellow River Basin and metropolitan areas, ultimately showcasing the power of machine learning in enhancing urban planning.

The application of space robotic manipulators and heightened autonomy for ios represents a paramount pursuit for leading space agencies, given the substantial threat posed by space debris to operational satellites and forthcoming space endeavors. This work presents a guidance algorithm based on drl to solve for the space manipulator path-planning during the motion synchronization phase with the mission target. The goal is the trajectory generation and control of a spacecraft equipped with a 7-dof robotic manipulator, such that its end effector remains stationary with respect to the target point of capture. The ppo drl algorithm is used to optimize the manipulator’s guidance law, and the autonomous agent generates the desired joints rates of the robotic arm, which are then integrated and passed to a model-based feedback linearization controller. The agent is first trained to optimize its guidance policy and then tested extensively to validate the results against a simulated environment representing the motion synchronization scenario of an ios mission.

The acoustic environment in learning spaces significantly influences learning effectiveness and occupant well-being. Recent studies have shown that a series of architectural factors within physical learning environments can impact students' educational experiences. This research delves into the relationship between architectural characteristics and the perceived acoustic environment among 467 primary students in 19 learning spaces across 9 schools in Chile. The survey comprises a student questionnaire, a checklist evaluating space characteristics, and acoustic measurements of indoor noise levels during occupied conditions. Examined topics include Indoor Environmental Quality (IEQ) comfort perception, noise annoyance, hearing ability, and acoustic preference. Architectural characteristics considered encompass flexible and acoustic space design parameters. The results indicated that noise discomfort was a common issue, especially in traditional learning spaces without acoustic treatment. The type of learning space (traditional or flexible settings) has a greater impact on acoustic perception particularly concerning noise discomfort and acoustic preference. However, poorly acoustic spaces lacking absorbing materials or exhibiting lower spatial density (m2 per student) contribute to increased indoor noise levels affecting noise annoyance caused by children's talking inside. The study emphasizes the importance of considering both architectural design and acoustic conditioning for optimizing the acoustic experience in educational spaces.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

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

Purpose: To evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in the study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5, Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS, Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). Individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only corneal fractal dimension remained significantly related to tear production (β = -0.26, p = 0.02) and only corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This highlights caution in using corneal nerve anatomy to predict corneal function.

The concept of Research Integrity and research ethics are linked to the scientific research process and its communication. Presenting the results objectively is essential. It turns out that few scientists use manipulation of results and consequently other types of misconduct such as data Fabrication, Falsification, and Plagiarism (FFP). In this article, we show the definitions of these and different aspects of behavior that should be avoided, which affect principles of research reliability. We present, through a brief literature review, the concept of Research Integrity, FFP, and its relations with Publish or Perish. Editorial disputes are linked to the power that scientists have to remain in the field of research, governed by clear rules to increase their intellectual capital. We discussed that scientists tend to want their papers published in journals with better impact and well-evaluated, seeking prominence in the publishing sector. We have seen that both scientists and journals can have sequelae and problems in the face of the Publish or Perish movement, which can call into question the quality of the editorial process, peer review, and the journal itself.

The paper examines the various uncertainties encountered in high-frequency trading (HFT) environments and delves into the multiple challenges faced by HFT firms in navigating the Dodd-Frank Wall Street Reform and Consumer Protection Act (referred to as the "Dodd-Frank Act"), particularly during the initial stages of its enactment. These challenges include the ambiguity surrounding the definition of HFT, the lack of clarity regarding regulatory requirements and boundaries, inconsistencies in enforcement resulting from deviations in understanding the content, and the absence of detailed descriptions of the Act’s provisions. These hurdles significantly impact not only the daily operations of HFT firms but also pose higher demands on their long-term strategic planning and risk management. Drawing upon the Data, Information, Knowledge, Wisdom, and Purpose (DIKWP) model, this study employs an innovative analytical framework. Through the comprehensive application of conceptual space, cognitive space, and semantic space, it provides a systematic methodology for identifying and analyzing the aforementioned issues. This approach not only aids firms in better comprehending and adhering to complex regulatory requirements but also enables them to explore new business opportunities and competitive advantages while ensuring compliance.

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

The scattering eigenstates of any Hamiltonian of electrons, coupled through a two-body force and moving on a one-dimensional lattice, are shown to be Bethe's wave-functions. The energy of the groundstate is compared with values, obtained previously for the Hubbard Hamiltonian by means of Bethe's wave-function and within the framework of the correlated Fermi gas. The same analysis is applied to electrons, interacting on neighbouring sites. The significance of those various groundstates is assessed with help of thermodynamics.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

The study was conducted to evaluate the agronomic performance, forage yield, and nutritive values of Desho grass varieties under supplementary irrigation at Dambi Dollo University experimental site, Western Ethiopia. Three Desho grass varieties (Areka /DZF#590, Kindu kosha-1/DZF #591, and Kulumsa /DZF #592) were arranged in randomized complete block design (RCBD) with three replications. The CROPWAT 8.0 model, local climate data, forage data, and soil data were used to determine Desho grass water requirements and irrigation schedules. The agronomic parameters, yield, chemical composition, and in vitro digestibility of the feed samples at standardization cut were determined following the standard procedures. The results showed significant differences (p

This study investigates the impact of rotor spacing on the aerodynamic performance of a coaxialcopter. It has been observed that a small distance between two rotors can result in significant interaction between the propellers, consequently affecting the rotor's aerodynamic efficiency. Exploiting this characteristic, the present research introduces a coaxialcopter with variable rotor spacing. Employing finite element numerical simulations, we assess the aerodynamic behavior of this novel configuration. Through comprehensive measurements and analysis of its aerodynamic performance across varying rotor spacings from 0.1R to 1R, we validate the effectiveness of a rotor spacing control strategy for enhancing takeoff maneuvers. Our numerical simulation results reveal that the performance characteristics of both upper and lower rotor converges toward that of a single rotor as pitch ratio increases, along with the reduce of their thrust fluctuations and aerodynamic performance periodicity. Considering stable power consumption patterns and endurance performance, we analysis the interrelations binding of pitch distance of the rotors, rotational speed, and pitch angle, vis-à-vis the thrust coefficient and power coefficient. Through parameter optimization method, we demonstrate that adjusting rotor spacing offers a practical means to enhance payload capacity without increasing power input, thereby improving the efficiency, which validates the practicality and efficacy of the parameter optimization approach. Furthermore, optimizing rotor spacing for specific operational scenarios enhances overall aerodynamic performance, suggesting a viable flight control strategy for takeoff and landing conditions.

With the increasingly online exposure of urban public spaces, the new concept of "Internet-celebrity cities" has emerged in China. The online internet-famous sites are the main characteristics of "Internet-celebrity cities". To fully understand online users' preferences in such kind of public spaces, this article took 27 typical riverfront internet-famous sites (RIFS) in Changsha city (China), as an example. Through the online images and review comments on social media platform "Xiaohongshu", the study analyzed users’ perception of RIFS specially on visual and emotional preferences. It revealed the following findings:(1) The popularity of RIFS had a significant head effect and there were far more positive emotions than neutral and negative emotions in review comments. (2) According to 5 different categories of RIFS: modern buildings with river views, restaurants with strong visual impact became the main attractions on commercial RIFS. The art exhibition RIFS attracted visitors to experience traditional culture and highlight their aesthetic pursuits. In the historical and cultural RIFS, people preferred to see the historical buildings with surrounding natural environment, as well as river and mountains views. Ecological Recreational RIFS showed the similar results with the uncultivated RIFS, for the main focus was on the ecological environment, a broader vision and the specific atmosphere. Moreover, the uncultivated RIFS showed more diversified attraction points. This study can provide a new perspective on the waterfront vitality and can offer a targeted and attractive manner for waterfront regeneration that are different from traditional methods.

The attitude dynamics and orbit dynamics of large rigid space structures are coupled with each other under gravity gradient, which may affect the stability of the large rigid space structures. In this paper, the gravity gradient stability of a large rigid space structure is studied under both small and large disturbances. Based on the rigid body dynamics and orbit dynamics, an accurate dynamic model without any linearization of the large rigid space structure is established via the natural coordinate formulation (NCF), which is able to describe the large overall motions of the structures. By using the generalized-α algorithm, the gravity gradient stability of the large rigid space structure is simulated and analyzed via various examples, including the influence of large disturbance angles, the positions at the stabilization and unstabilization regions. Finally, the relationship between spinning stability and gravity gradient stability is also investigated via a large spinning space structure.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Laser in situ keratomileusis (LASIK) is the gold standard in the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap by a femtosecond laser, ablation of the underlying stromal bed by an excimer laser, and reposition of the flap. The corneal flap can be build in a 2-dimension (2D) fashion with tapered edges, or in a 3-dimension (3D) fashion, with angled sidecut. The latter reduces the risk of flap dislocation and infiltration of epithelial cells. This retrospective study compares with optical coherence tomography 3D and 2D flaps, and respective intra- and early post-operative complications. Four hundred consecutive eyes were included, 200 for each group. In the 3D group, the mean edge angle was 92°. The procedure was in average 5.2 seconds slower in the 3D group (p=0). Non visually significant flap folds were found in 13 eyes of the 2D group and in 7 eyes of the 3D group (p= 0.17). An intracorneal opaque bubble layer induced by laser photodisruption was more commonly observed in the 3D group (9 eyes vs. 2; p=0.03). In conclusion, the creation of a LASIK flap by a 3D-femtosecond laser cut was safe and effective.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

Suppose for n∈ ℕ, set A⊆ℝⁿ and function f∶A→ℝⁿ. If set A, using the Hausdorff outer measure, is measurable in the sense of Carathèodory; we want to find an extension of the expected value, w.r.t the Hausdorff measure, that's unique, finite and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. The issue is current extensions of the expected value are finite for all functions in only a shy subset of ℝᴬ. The reason this issue wasn't resolved is mathematicians have not thought of the problem, focusing on application rather than generalization. Despite the lack of potential use, we'll attempt to solve the problem by defining a choice function---this shall choose a unique set of equivalent sequences of sets (Fₖ***) , where the set-theoretic limit of Fₖ*** is the graph of f; the measure Hʰ is the ℎ-Hausdorff measure, such for each k∈ℕ, 0 < Hʰ(Fₖ***) < +∞; and (fₖ*) is a sequence of functions where {(x,fₖ*(x))∶x∈ dom(Fₖ***)}=Fₖ***. Thus, the extended expected value of or E**[f,Fₖ***] is: ∀(ε>0)∃(N∈ℕ)∀(k∈N)(k≥N⇒1/Hʰ(dom(Fₖ***))∫dom(Fₖ*** )fₖ* dHʰ - E**[f,Fₖ***]<ε ) which should be unique, finite, and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. Note we guessed the choice function using computer programming but we don’t use mathematical proofs due to the lack of expertise in the subject matter. Despite this, the biggest use of this research is the extension of the expected value is finite for "almost all" functions: this is easier to use in application when finding the "average" of functions covering an infinite expanse of space.

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

Green open spaces (GOS) are well known to be vital to enhancing the standard of living conditions in urban environments. The World Health Organization (WHO) says it is important to have at least nine square meters per citizen. The European Environment Agency (EEA) stipulates that 5000 square meters of green space will be reachable within 300 meters to residents. GOS pattern in Kyrenia Region is not adequate or successful in that regard. The process of urban planning has been neglected in the Kyrenia region and these areas have lost their significance and value. This research evaluates the level of accessibility of green spaces in Kyrenia Region. Three urban areas, Kyrenia, Karavas and Agios Epiktitos have been analyzed within this framework. In order to do that, GOS areas and their pattern are researched by deploying geographical information analysis. Accessibility to these areas is measured by using Euclidean and network distance analysis based on 300, 800 and 5000 meters. Mainly, Euclidean distance and network distance methods are measured from building units and results showing accessibility values are constructed. According to the results, network accessibility is very low within the study region. Additionally, Kyrenia, Karavas and Agios Epiktitos have shortage in GOS per capita. To offer effective strategies for urban planning, the factors influencing the accessibility and also the usage of GOS are addressed.

Quantum physics is intrinsically probabilistic. The entropy of a quantum state quantifies the amount of randomness (or information loss) of such state. The degrees of freedom of a quantum state are position and spin, and upon their specification Born's rule in phase space defines randomness. We focus on the spin degree of freedom and elucidate the spin entropy. Then, we present some of its properties and show how entanglement increases spin entropy. Some speculative predictions on the decay of the $Z^0,W^{+,-}$ gauge bosons conclude the paper.

The author introduces a novel theoretical framework that suggests matter and energy are both converted from curved space. In Space Theory, gravitation is generated by the flow of space, instead of being transmitted by the graviton as in String Theory. This theory also suggests that Newton's gravitational constant, denoted as G, may not be truly constant but could vary over time. The equivalent equation of space is S=Ec²=mc⁴, and the gravitation of hollow sphere space is S_μν=4πGm=(4/3)π((r+a)³-r³). The Space Theory also predicts that the surface gravitational acceleration of the neutron star Crab Pulsar (PSR B0531+21) is approximately 8.21924883×10⁶ m/s².

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Based on recent progress in cosmological thermodynamics, we present a new thermody- namic formulation of the Friedmann equations in the new Haug-Tatum cosmology model, as well as for other similar models put forward in the literature from different solutions to Einstein’s field equation. Since the CMB temperature has been measured much more accu- rately than the Hubble constant, we demonstrate that our thermodynamic formulation of the Friedmann equation dramatically narrows the acceptable range for the critical density of the universe. Furthermore, we show how our thermodynamic formulation leads to a more precise cosmological constant estimate.

Agricultural activities are the second largest source of greenhouse gas emissions, and carbon emissions from agricultural land use (CEALU) have become a hot issue across the world. However, few scholars explored the impact of agricultural land policies on carbon emissions, such as the High-standard farmland construction(HSFC) in China.Thus，by relying on provincial panel data for China for the period 2005-2017, the effect of the high-standard basic farmland construction policy on carbon emissions from agricultural land use per unit area and its regional differences were quantitatively analyzed using the difference-in-difference (DID) model. The results showed that: 1) China's CEALU per unit area presented a fluctuating upward trend during the period 2005-2017, from 392.58 kg/ha to 457.72 kg/ha, with an average annual growth rate of 1.31%. 2) The high-standard farmland construction(HSFC) policy produced a significant carbon emission reduction effect in agricultural land use, and reduced the CEALU per unit area by 10.80% on average. With the promotion of this policy, its carbon emission reduction effect in agricultural land use presented an overall increasing trend. 3) The carbon emission reduction effect of the high-standard farmland construction policy in agricultural land use was significant in central China, but non-significant in eastern China and western China.

Euler-Poisson equations of a charged symmetrical body in external constant and homogeneous electric and magnetic fields are deduced starting from the variational problem, where the body is considered as a system of charged point particles subject to holonomic constraints. The final equations are written for the center-of mass-coordinate, rotation matrix and angular velocity. General solution to the equations of motion is obtained for the case of a charged ball. For the case of a symmetrical charged body (solenoid), the task of obtaining the general solution is reduced to the problem of a one-dimensional cubic pseudo-oscillator. Besides, we present a one-parametric family of solutions to the problem in elementary functions.

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

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

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

Abstract: This article aims to better understand the mechanisms that connect climate change perceptions and general willingness to engage in pro-environmental behavior using Spanish cross-sectional data (N = 403). To do this, we first developed and validated the General Willingness for Environmental Behavior Scale (GWEBS), which includes the classical approach of voluntarily doing new actions but also actions implying not doing things (degrowth) and actions forced by social constraints. The exploratory and confirmatory factor analysis showed a good fit for the one-factor structure, which had adequate validity based on their relationship with other variables. Additionally, the GWEBS distinguished between women and men, left- and right-oriented people, and people who belonged to pro-environmental groups and people who did not. In the second place, we tested the parallel mediator role of eco-anxiety and trust in science in the relationship between climate change perceptions and the GWEBS. The results showed that eco-anxiety, fully, and trust in science partially mediated such a relationship, making them crucial to mobilize the intention to act following the perception. This study contributes to our understanding of the psychological mechanisms that eventually drive pro-environmental behaviors and provides a clear direction for future research.

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

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

The classical Lotka-Volterra predator-prey model is globally stable and uniformly persistent. However, in real-life biosystems extinction of species due to stochastic effects is possible. In this paper, we consider the classical Lotka-Volterra predator-prey model under stochastic perturbations. For this model, using an analytical technique based on the direct Lyapunov method and a development of the ideas of R.Z. Khasminskii, we find the precise sufficient conditions for the stochastic extinction of one and both species and the precise necessary conditions for the stochastic system persistence. The stochastic extinction occurs via a process known as the stabilization by noise of the Khasminskii type, and, in order to establish the sufficient conditions for extinction, we found the conditions for the stabilization. The analytical results are illustrated by numerical simulations. {\bf Keywords:} stochastic perturbations, white noise, Ito's stochastic differential equation, the Lyapunov functions method, stability in probability, stabilization by noise, stochastic extinction, persistence.

Spatial planners are nowadays strongly interested in the benefits of greenspace for the health of urban residents. However, concrete and context-specific guidance on effective greening strategies is still lacking. We present a novel, model-based approach to support the development of such strategies. The approach is quantitative and spatially-explicit, and accounts for multiple health benefits as well as burdens. In this study, we applied the approach to the city of Maastricht (The Netherlands), and conducted an integrated, city-scale assessment of the health benefits and burdens of four urban greenspace designs. These included: ‘No greenspace’, ‘Current greenspace’, ‘Green parking lots and squares’, and ‘Optimized greenspace locations’. For each greenspace design, indicator values were calculated for five health determinants: heat stress, air pollution, perceived unsafety, unattractive views, and tick-bite risk. To assess the health contribution of urban greenspace in a given design, these indicator values were compared with the values in the ‘No greenspace’ design. The study produced clear, quantitative conclusions about the health benefits and burdens of the urban greenspace designs for the case of Maastricht, but also generated novel, more general insights relevant to planning of urban greenspace for health. These insights concern the importance of translating health policy objectives into specific target values or thresholds, and the importance of ‘smart’ choices in greenspace type and location that can effectively reduce trade-offs between health benefits and burdens. Priorities for future research, addressing limitations of the presented approach, concern a further expansion of the range of health benefits and burdens covered by the model, and the development of a common metric for the entire range of health benefits and burdens allowing optimization of greenspace design to maximize its overall net health benefit.

This study empirically analyzes the effectiveness of resource optimization utilizing artificial intelligence (AI) within cloud computing environments. It compares systems that have been transitioned from a Monolithic structure to Microservices Architecture (MSA) with those adopting a simple Rehost strategy, to validate the operational efficiency of two systems whose resource efficiency has been enhanced compared to traditional legacy systems. The research is based on systems that determined resource efficiency post-cloud migration using APM tools. It points out the limitations of traditional heuristic operation methods in resource optimization, which lead to issues such as application performance degradation, resource over-allocation, and increased operational costs. This study aims to overcome the conventional resource optimization standards that depended on the average peak usage of CPU and memory infrastructure, by introducing AI-based optimization tools, and applying on-premise standards to cloud and container environments to achieve resource optimization. The paper emphasizes the importance of resource optimization through AI-based automation tools, exploring the possibilities of resolving real-world application performance issues in cloud environments, reducing unnecessary resource usage costs, and cutting down on labor risks and operational expenses. Through this, it presents strategic directions on how AI technology can offer financial and operational advantages in managing cloud resources.

Mango (Mangifera indica L.) is an allotetraploid (2n = 4X= 40) drupe fruit and has high nutritional value belongs to genus Mangifera and family Anacardiaceae. Mango cultivars are used with worldwide acceptance to pharmacological, ethnomedical, and phytochemical industries. Assessment of the genetic distinctiveness of a cultivar through morphological descriptors is an important tool for both the registration and the protection. New mango genotypes have been improved using valuable diverse germplasm resources to ensure food security. DNA fingerprinting based simple sequence repeats (SSR)-markers have been the most broadly used, effective and accurate in evaluation of genetic characterization of a cultivar. Molecular breeding is an effective source of genetic gain after improvement of fruit trees using marker assisted genomic selection. Total genomic DNA (gDNA) was generated using CTAB method from each cultivar. The most effective 50 hyper-variable SSR markers were selected. Highly specific DNA fingerprints were identified in the candidate line ‘Azeem Chaunsa’ compared with three standard cultivars using SSR-PCR. An agglomerative hierarchical clustering method was used to construct dendrogram based on the UPGMA clustering method. Cultivar identification diagram (CID) was constructed to evaluate association among standard cultivars and Azeem Chaunsa. Our results showed that SSR markers could efficiently assess genetic diversity in mango. The genetic similarity coefficients were recorded between the cultivars of mango ranged from 0.49 to 0.67. CID results concluded that cultivar ‘Azeem Chaunsa’ varied significantly from the check cultivar, Sindhri (46.2%), S.B Chaunsa (45%) and Sufaid Chaunsa (46.7%). The results obtained in this study will orient cultivar identification strategies for a successful future.

Transformation formula under the action of a general linear fractional transformation for generalized Dedekind eta-function has been a subject of intensive study, Rademacher, Dieter, Meyer et al. However, the (Hecke) modular relation structure has not been recognized until the work of Goldstein-de la Torre, and streamlining the classical proofs in the modular relation will reveal the meaning hidden in those works. Our main aim is to elucidate the works of these researchers in the context of modular relations.

A cyclic antipodal points of a circle is a pair of points that are the intersection of the circle with a diameter of the circle. A recent proof of Ptolemy’s Theorem, simultaneously in both (i) Euclidean geometry; and (ii) the relativistic model of hyperbolic geometry (which is identified with the Klein model of hyperbolic geometry), motivates in this article the study of four cyclic antipodal points of a circle, ordered arbitrarily counterclockwise. The translation of results from Euclidean geometry into hyperbolic geometry is obtained by means of hyperbolic trigonometry, called gyrotrigonometry, to which Einstein addition gives rise. Formulas that extend the Pythagorean formula in both Euclidean and hyperbolic geometry are obtained as byproducts

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

The Simulation analogy presented in this work enhances the accessibility of abstract quantum theories, specifically the stochastic hydrodyanimc model (SQHM), by relating them to our daily experiences. The SQHM incorporates the influence of fluctuating gravitational background, resembling dark energy, into quantum equations. This model successfully addresses key aspects of Objective-Collapse Theories, including resolving the 'tails' problem through the definition of quantum potential length in addition to the De Broglie length, beyond which coherent Schrödinger quantum behavior and wavefunction tails cannot be maintained. The SQHM emphasizes that an external environment is unnecessary, asserting that the quantum stochastic behavior leading to wave-function collapse can be an inherent property of a system in a spacetime with fluctuating metrics. Embedded in relativistic quantum mechanics, the theory establishes a coherent link between the uncertainty principle and the constancy of light speed, aligning seamlessly with finite information transmission speed. Within a fluctuating quantum system, the SQHM derives the indeterminacy relation between energy and time, offering insights into measurement processes impossible within a finite time interval in a truly quantum global system. Experimental validation is found in confirming the Lindemann constant for solid lattice melting points and the transition from fluid to superfluid states. The SQHM's self-consistency lies in its ability to describe wavefunction collapse and the measure process. Additionally, the theory resolves the Pre-existing Reality problem by showing that large-scale systems naturally decay into decoherent states stable in time. Continuing, the paper demonstrates that the physical dynamics of SQHM can be analogized to a computer simulation employing optimization procedures for realization. This perspective elucidates the concept of time in contemporary reality and enriches our comprehension of free will. The overall framework introduces an irreversible process impacting the manifestation of macroscopic reality at the present time, asserting that the multiverse exists solely in future states, with the past comprising the formed universe after the current moment. Decoherence at the present time functions as a reduction of the multiverse to a single universe. The macroscopic reality, characterized by fractal consistency where microscopic domains with quantum properties coexist, provides insights into how our consciousness apprehends dynamic reality, the spontaneous emergence of gravity in discrete spacetime evolution, and the attainment of the classical General Relativity limit in Quantum Loop Gravity and Causal Dynamical Triangulation. The Simulation Analogy highlights a strategy focused on minimizing information processing, facilitating the universal simulation in solving its predetermined problem. From within, reality becomes the manifestation of specific physical laws emerging from the inherent structure of the simulation devised to address its particular issue. In this context, the reality simulation appears to employ an entropic optimization strategy, minimizing information loss while efficiently compressing data in line with the simulation's intended purpose.

In the present study. At first, some properties of r-fuzzy soft β-closed sets are introduced on fuzzy soft topological spaces based on the paper Aygunoglu et al. (Hacet. J. Math. Stat. 2014, 43, 193-208). Also, we define the closure and interior operators with respect to the classes of r-fuzzy soft β-closed and r-fuzzy soft β-open sets, and investigate some of their properties. In addition, the concept of r-fuzzy soft β-connected sets is introduced and characterized with help of fuzzy soft β-closure operators. Thereafter, some properties of a fuzzy soft β-continuity are studied. Furthermore, we introduce and study the concepts of fuzzy soft almost (weakly) β-continuous functions, which are weaker forms of a fuzzy soft β-continuity. Also, the relationships between these classes of functions are specified with the help of some illustrative examples. Finally, we explore new types of fuzzy soft functions called, fuzzy soft β-irresolute (strongly β-irresolute, β-irresolute open, β-irresolute closed and β-irresolute homeomorphism) functions, and discuss some properties of them. Also, we show that fuzzy soft strongly β-irresolute → fuzzy soft β-irresolute → fuzzy soft β-continuity, but the converse may not be true.

The growing impact of Artificial Intelligence (AI) on Humanity is unavoidable, and therefore, “AI literacy” is extremely important. In the field of education – AI in education (AIED) – this technology is having a huge impact on the educational community and on the education system itself. The present study seeks to assess the level of AI literacy of teachers at Portalegre Polytechnic University (PPU), aiming to identify gaps, find the main opportunities for innovation and development and seek the degree of relationship between the dimensions of AI literacy, as well as identifying the predictive variables in this matter. As a measuring instrument, a validated questionnaire based on three dimensions (AI Literacy, AI Self-Efficacy and AI Self-Management) was applied to a sample of 75 teachers in the various schools of PPU. This revealed an average level of AI literacy (3.28), highlighting that 62.4% of responses are at levels 3 and 4 (based on a Likert scale from 1 to 5). The results also demonstrate that the first dimension is highly significant for the total dimensions, i.e., for AI Literacy, and no factor characterizing the sample is a predictor, but finding a below-average result in the Learning factor indicates a pressing need to focus on developing these skills.

Let $(\{f_n\}_{n=1}^\infty, \{\tau_n\}_{n=1}^\infty)$ and $(\{g_n\}_{n=1}^\infty, \{\omega_n\}_{n=1}^\infty)$ be unbounded continuous p-Schauder frames ($0<p<1$) for a disc Banach space $\mathcal{X}$. Then for every $x \in ( \mathcal{D}(\theta_f) \cap\mathcal{D}(\theta_g))\setminus\{0\}$, we show that \begin{align}\label{UB} \|\theta_f x\|_0\|\theta_g x\|_0 \geq \frac{1}{\left(\displaystyle\sup_{n,m \in \mathbb{N} }|f_n(\omega_m)|\right)^p\left(\displaystyle\sup_{n, m \in \mathbb{N}}|g_m(\tau_n)|\right)^p}, \end{align} where \begin{align*} & \theta_f: \mathcal{D}(\theta_f) \ni x \mapsto \theta_fx \coloneqq \{f_n(x)\}_{n=1}^\infty\in \ell^p(\mathbb{N}), \quad \theta_g: \mathcal{D}(\theta_g) \ni x \mapsto \theta_gx \coloneqq \{g_n(x)\}_{n=1}^\infty\in \ell^p(\mathbb{N}). \end{align*} Inequality (1) is unexpectedly different from both bounded uncertainty principle \textit{[arXiv:2308.00312v1]} and unbounded uncertainty principle \textit{[arXiv:2312.00366v1]} for Banach spaces.

This study introduces a specialized Automatic Speech Recognition (ASR) system, leveraging the Whisper Large-v2 model, specifically adapted for radiological applications in French language. Our methodology focused on adapting the model to accurately transcribe medical terminology and diverse accents within the French language context, achieving a notable Word Error Rate (WER) of 17.121%. The research involved extensive data collection and preprocessing, utilizing a wide range of French medical audio content. The results demonstrate the system's effectiveness in transcribing complex radiological data, underscoring its potential to enhance medical documentation efficiency in French-speaking clinical settings. The discussion extends to the broader implications of this technology in healthcare, including its potential integration with Electronic Health Records (EHRs) and its utility in medical education. The study also explores future research directions, such as tailoring ASR systems to specific medical specialties and languages. Overall, this research contributes significantly to the field of medical ASR systems, presenting a robust tool for radiological transcription in the French language and paving the way for advanced technology-enhanced healthcare solutions.

SARS-CoV-2 Omicron variant spike RBD epitopes in complex with spike (S) -protein D614G mutations now predominate globally and increase infectivity by assembling more functional S proteins into the virion. On average, homeopathic medicine contains less than one molecule per dose on average. Single variable SphericalHarmonicY, LaguerreL, WhittakerM, SphericalBesselJ, LegendreP, LegendreQ, LaguerreL, ChebyshevT, and Hypergeometric1F1 Functions pFqarise in connection with the power series solution of the Schrodinger equation or in the summation of perturbation expansions in quantum mechanics. A quantum interpretation of the homeopathic method is presented here through a novel algebraic topology approach to supersymmetry and symmetry breaking in quantum fields and quantum gravity theory with the aim of developing a wide range of physical-based drug design applications in a Small Molecule Quantized Water Memory Network suggesting that the Hidden Black Hole Paradox of Information Loss might be solved under suitable conditions.

The progress in markerless technologies is bringing clinicians tools to rapidly evaluate tests such as Timed Up and Go (TUG) without compromising the time of the assessment, yet it raises questions about the potential trade-off in accuracy compared to traditional marker-based systems, suggesting that the precision of these evaluations is not yet conclusively established. The OpenCap system is an easy tool to process 3D kinematics with two iPhone cameras placed in front of the subject. Previous research has primarily focused on walking and movement towards the cameras with the subject facing the cameras (WF) and thus has been unable to disentangle the differences in the movement directions. We have compared the OpenCap system with a standard marker-based system for both walking directions. In OpenCap, we found significantly worse results capturing walking facing away from the cameras (RW). Compared to the marker-based system, our findings indicate troubles measuring kinematic parameters but provide good accuracy in measuring spatial-temporal parameters. These insights pave the way for refining markerless assessment technologies, potentially enhancing their utility in clinical settings.

Urban rivers and waterfronts play a vital role in the ecological, social, and economic fabric of cities, providing not only aesthetic value but also serving as important ecosystems that contribute to the overall well-being of urban environments. However, many urban rivers, including the Beirut River in Lebanon, face challenges such as pollution, neglect, and the loss of recreational and ecological value due to urbanization and industrialization. According to the Lebanese MOE (Ministry of Environment), almost 70% of Lebanese rivers are polluted due to untreated waste management systems and which leads to undrinkable water and possible flooding disasters if not treated. This study addresses the problem of abandoned and degraded spaces along the Beirut River riverside through the application of urban acupuncture, a strategic approach that targets specific points in the urban environment to stimulate positive change and regeneration. The aim of the study is to assess the effectiveness of implementing small-scale ‘sensitive urban points’ known as urban acupuncture as the method for regenerating the Beirut River riverside, with the hypothesis that targeted interventions through Blue Urban Acupuncture or Aqua-puncture- can lead to significant improvements in the ecological, social, and economic aspects of the area that re-connect the people of Beirut with its river. The methodology involves a multidisciplinary approach that integrates urban design, and community engagement, and analysing similar examples of different approaches through creating a comparative table. Data collection includes environmental assessments of water quality, biodiversity, and ecosystem health, as well as social surveys to understand community needs and perceptions. By applying urban acupuncture principles to the Beirut River riverside, this study seeks to demonstrate how strategic interventions can lead to the regeneration of abandoned spaces, improve the overall quality of the urban environment, and create sustainable and inclusive riverside landscapes that benefit both the environment and the community.

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