Suicidal behaviour remains difficult to predict and prevent, even for experienced mental health care professionals. The known distal risk factors for suicidal behaviour are not sufficiently specific to fully understand the complex dynamic processes that precede a suicide attempt. Real-time mobile monitoring data can be used to analyse proximal risk mechanisms within the suicidal process. At the same time smartphone-based safety planning and self-monitoring may enhance a patient’s self-management skills thereby increasing their capacity to respond to a suicidal crisis and to become more aware of crisis symptoms. The current paper describes the theoretical and conceptual rationale for the CASPAR study which applies an innovative approach to the study of suicidal processes. It uses basic science approaches to inform the implementation of an innovative suicide prevention intervention. We aim to develop and implement mobile safety plan in conjunction with real-time monitoring in order to both directly implement suicide prevention interventions and to study the ongoing dynamics of individual suicidal behaviour by applying network analysis.

Digital health has added numerous promising solutions to enhance the health and wellness of people with neurocognitive disorders (NCDs) and their informal caregivers: (1) Background: It is important to get a comprehensive view of currently available technologies, their outcomes, and conditions of success to inform recommendations regarding digital health solutions for people with NCDs and their caregivers. This environmental scan was performed to identify the features of existing digital health solutions relevant to the targeted population. This work reviews currently available digital health solutions and their related characteristics to develop a decision support tool for older adults living with mild or major neurocognitive disorders and their informal caregivers. This knowledge will inform the development of a decision support tool to assist older adults and their informal caregivers in their search for adequate digital health solutions according to their needs and preferences, based on trustable information.; (2) Methods: We conducted an environmental scan to identify digital health solutions from a systematic review and targeted searches in grey literature covering the regions of Canada and Europe. Technological tools were scanned based on a preformatted extraction grid. We assessed their relevance based on selected attributes and summarized findings; (3) Results: We identified 100 available digital health solutions. The majority (56%) were not specific to NCDs. Only 28% provided scientific evidence of their effectiveness. Remote patient care, movement tracking, and cognitive exercises were the most common purposes of digital health solutions. Most solutions were presented as decision aid tools, pill dispensers, apps, web, or a combination of these platforms. (4) Conclusions: This environmental scan allowed the identification of current digital health solutions for older adults with mild or major neurocognitive disorders and their informal caregivers. Findings from the environmental scan highlight the need for additional approaches to strengthen digital health interventions for the well-being of older adults with mild and major NCDs and their informal and formal healthcare providers.

Salidroside, a valuable phenylethanoid glycoside, is obtained from plants belonging to the Rhodiola genus, known for its diverse biological properties. At present, salidroside is still far from large-scale industrial production due to the lower titer and higher process cost. In this study, we constructed a biosynthetic pathway from L-tyrosine to salidroside in Saccharomyces cerevisiae. To increase sali-droside production, we for the first time constructed an in vivo UDP-glucose regeneration system that sucrose synthase GmSUS worked in conjunction with UDP-glucose transferase RrUGT33 to improve the UDP-glucose availability with inexpensive sucrose as the consumed substrate. Finally, the molar conversion rate of L-tyrosine could reach 95%. To further reduce the cost, co-culture with E. coli that synthesized L-tyrosine de novo resulted in an 81% reduction in the final substrate cost per 1 kg of salidroside compared to the initial cost. The final titer of salidroside obtained 3.8 g/L and was the highest titer achieved at the Shake-Flask-Level in the existing reports. And this marked the first successful synthesis of salidroside in an in situ enhanced UDP-glucose system using sucrose. This accomplishment laid a robust groundwork for further investigations into the synthesis of other notable glycosides and natural compounds.

The successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening for potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipig and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. Here, we determined the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus - 1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) efficiently and used the methods to screen indigenous Greek black pigs. Since porcine endogenous retroviruses (PERVs) of type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and very resistant to diseases.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

Understanding surface water evaporation in tropical catchments is pivotal for effective water management, but limited research exists on stable isotopic (δ2H and δ18O) assessment of water evaporation losses. Our study bridges that gap, examining stable isotopes in meteoric water and surface waters across tropical regions, both humid and semi-arid. Using the Craig-Gordon model, we calibrated evaporation-to-inflow (E/I) ratios, identifying distinct E/I variations between seasons and regions. Notably, the semi-arid region consistently exhibited higher E/I ratios due to climatic characteristics. By integrating the Hamiltonian Monte Carlo and the No-U-Turn Sampler, we were able to quantify uncertainties in isotopic and meteorological parameters, resulting in E/I estimates within 68% and 95% confidence intervals. Our Bayesian model insights are critical for freshwater resource optimization and hydrological modeling in tropical regions.

With the rise of internet technology and the growth of mobile communications, the global economy has undergone a significant transformation, shifting towards digital and soft markets. As a result, great efforts have been made to establish virtual marketplaces that provide customers with an exceptional shopping experience. One crucial aspect of this new paradigm is marketing, which has led to the emergence of a new stage known as E-marketing. In E-marketing, understanding customer behavior is of utmost importance. Marketing teams and companies are eager to gain insights into how different customer segments react to their products. Marketing strategies are now developed based on customer information such as financial status, location, age, gender, and more. As a result, the abundance of customer data generated by these new commerce technologies has surpassed the capabilities of traditional data analysis methods. To extract valuable knowledge from this vast amount of data, data mining technologies have come into play. Techniques such as clustering, classification, and prediction are utilized to mine marketing data and uncover hidden patterns and trends. The impact of data mining on E-marketing has been the subject of analysis in this study. A questionnaire-based review was conducted to collect the necessary data, which was then analyzed using SPSS 23 software. The study's results demonstrate that data mining can significantly enhance the performance of E-marketing by providing intelligent and efficient predictions of customer behaviour. Moreover, this technology offers similar advantages for end-customers as well. By leveraging the power of data mining, companies can gain valuable insights, tailor their marketing efforts, and ultimately provide better products and services to their customers in the digital marketplace.

NUSES is a planned space mission aiming to test innovative observational and technological approaches related to the study of low-energy cosmic rays, gamma rays and high-energy astrophysical neutrinos. Two scientific payloads will be hosted onboard the NUSES space mission: Terzina and Zirè. Terzina will be an optical telescope readout by SiPM arrays, for the detection and study of Cerenkov light emitted by Extensive Air Showers generated by high-energy cosmic rays and neutrinos in the atmosphere. Zirè will focus on the detection of protons and electrons up to a few hundred MeV and to 0.1-10 MeV photons and will include the Low Energy Module (LEM). The LEM will be a particle spectrometer devoted to the observation of fluxes of low-energy electrons in the 0.1-7 MeV range and protons in the 3-50 MeV range along the Low Earth Orbit (LEO) followed by the hosting platform. The detection of Particle Bursts (PBs) in this Physics channel of interest could give new insight into the understanding of complex phenomena such as eventual correlations between seismic events or volcanic activity with the collective motion of particles in the plasma populating van Allen belts. With its compact sizes and limited acceptance, the LEM will allow the exploration of hostile environments such as the South Atlantic Anomaly (SAA) and the inner van Allen belt, in which are expected electron fluxes of the order of 106−7 cm−2 sr−1 s−1. Concerning the vast literature of space-based particle spectrometers, the innovative aspect of the LEM resides in its compactness, within 10x10x10 cm3, and in its “active collimation” approach dealing with the problem of multiple scattering at these very low energies. In this work, the geometry of the detector, its detection concept, its operation modes and the hardware adopted will be presented. Some preliminary results from the Monte Carlo simulation (Geant4) will be shown.

To study and monitor the adverse health consequences from using electronic cigarettes, a user’s puff topography, which are quantification parameters of the user’s vaping habits, plays a central role. In this work, we introduce a topography sensor to measure the mass of total particulate matter generated in every puff and to estimate the nicotine yield. The sensor is compact and low-cost, and is integrated into the electronic cigarette device to promptly and conveniently monitor the user’s daily puff topography. The topography sensor is comprised of a photometric sensor and a pressure sensor. The photometric sensor measures the mass concentration of the aerosol, based on scattering of near-infrared light from airborne particles, while the pressure sensor measures the flow rate. The topography sensor was experimented under various conditions with a wide range of atomizer power, puff duration, and inhalation pressure. The sensor’s accuracy was validated by comparing the sensor’s readings with reference measurements, and the results matched closely with the trends reported by existing studies on electronic cigarettes. An example application of tracking a user’s puff topography was also demonstrated. Our topography sensor holds great promise in mitigating health risks of vaping, and in promoting quality control of electronic cigarette products.

The importance of measuring sustainability in tourism has been significantly advancing in recent years, following the need to manage the impact of tourism on territories and hosting communities. It was further boosted by the pandemic, where sustainability has been defined as one of the central elements to restart global tourism. The ETIS model, developed by the European Commission, is a point of reference based on self-assessment, data collection and analysis by the destinations themselves. The application of ETIS toolkit has faced many challenges, especially at sub-national level, mostly related to the lack of available and updated data to feed the model. The hypothesis explored by the authors is to solve the implementation issues, developing an indicator based on the use of the Sentiment Analysis to frame e-reputation and tourism satisfaction, and further combining it with other open data sources. The Tourism Sustainability Index (TSI) can provide a scalable and geo-referenced evaluation of tourism sustainability, measuring the four pillars and sub-components referenced to ETIS criteria, applicable to any tourism destination. Results show that the TSI can be seen as a consistent and valid tool for destinations to analyze sustainability, monitor its evolution through time periods and sub-areas, and compare it to other benchmark or competitive areas.

BackgroundIt is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals plays a role. MethodsWe used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. ResultsThe prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ=0.55; P<0.001], K. pneumoniae [ρ=0.58; P<0.001]; A. baumanii [ρ=0.54; P=0.004]; P. aeruginosa [ρ=0.48; P=0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. ConclusionsReducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various gram negative bacterial species.

Studies have shown that aerosols generated from flavored e-cigarettes contain Reactive Oxygen Species (ROS), promoting oxidative stress-induced damage within pulmonary cells. Our lab investigated the ROS content of e-cigarette vapor generated from disposable vape bars, a product exempt from the Federal Drug Enforcement Agency’s (FDA) 2020 flavor ban. Specifically, we analyzed vape bars belonging to multiple flavor categories (Tobacco, Minty Fruit, Fruity, Minty/Menthol, Desserts, and Drinks), manufactured by various vendors and of various nicotine concentrations (0-6.8%). Aerosols from these flavored vape bars were generated by a single puff aerosol generator and individually bubbled through a fluorogenic solution to detect and semi-quantify ROS in H2O2 equivalents generated by the vape bars. We compared and contrasted the ROS levels generated by each flavor as an indirect determinant of oxidative stress potential by these disposable vape bars. Our results showed that ROS concentration (μM) of aerosols produced from the vape bars varied significantly between different flavors and a function of nicotine concentration. Likewise, our results suggest that flavoring chemicals and nicotine concentration play a role in alerting ROS production in e-cigarette aerosols. Our study provides insight into the differential health effects of flavored disposable vape bars and the need for their regulation.

A significant attention has been made to the accurate detection of diabetes which is a big challenge for the research community to develop a diagnosis system to detect diabetes in a successful way in the IoT e-healthcare environment. Internet of Things (IOT) has emerging role in healthcare services which delivers a system to analyze the medical data for diagnosis of diseases applied data mining methods. The existing diagnosis systems have some drawbacks, such as high computation time, and low prediction accuracy. To handle these issues, we have proposed a IOT based diagnosis system using machine learning methods, such as preprocessing of data, feature selection, and classification for the detection of diabetes disease in e- healthcare environment. Model validation and performance evaluation metrics have been used to check the validity of the proposed system. We have proposed a filter method based on the Decision Tree (Iterative Dichotomiser 3) algorithm for highly important feature selection. Two ensemble learning Decision Tree algorithms, such as Ada Boost and Random Forest are also used for feature selection and compared the classifier performance with wrapper based feature selection algorithms also. Machine learning classifier Decision Tree has been used for the classification of healthy and diabetic subjects. The experimental results show that the Decision Tree algorithm based on selected features improves the classification performance of the predictive model and achieved optimal accuracy. Additionally, the proposed system performance is high as compared to the previous state-of-the-art methods. High performance of the proposed method is due to the different combinations of selected features set and GL, DPF, and BMI are more significantly important features in the dataset for prediction of diabetes disease. Furthermore, the experimental results statistical analysis demonstrated that the proposed method would be effectively detected diabetes disease and can easily be deployed in IOT wireless sensor technologies based e-healthcare environment.

Exploring the dynamic behavior of cellular metabolism requires a standard laboratory method that guarantees rapid sampling and extraction of the cellular content. We propose a versatile sampling technique applicable to cells with different cell wall and cell membrane properties. The technique is based on irreversible electroporation with simultaneous quenching and extraction by using a microfluidic device. By application of electric pulses in the millisecond range, permanent lethal pores are formed in the cell membrane of Escherichia coli and Saccharomyces cerevisiae, facilitating the release of the cellular contents; here demonstrated by the measurement of glucose-6-phosphate and the activity of the enzyme glucose-6-phosphate dehydrogenase. The successful application of this device was demonstrated by pulsed electric field treatment in a flow-through configuration of the microfluidic chip in combination with sampling, inactivation, and extraction of the intracellular content in a few seconds. Minimum electric field strengths of 10 kV/cm for E. coli and 7.5 kV/cm for yeast S. cerevisiae were required for successful cell lysis. The results are discussed in the context of applications in industrial biotechnology, where metabolomics analyses are important.

Immunosensors have been widely developed to use antibodies to detect a pathogen of interest; it is interesting to look at the effect of nonspecific antibody binding to E. coli using electrochemical methods. IgG antibody not specific to E. coli O157:H7 was crosslinked onto a screen-printed carbon electrode. The presence of E. coli at 4, 4 × 10², 4 × 10⁵, and 4 × 10⁸ CFU/mL on the electrode surface was detected via linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS). Current transfer at both electrodes was reduced as the concentration of bacteria increased; however, the calibration of number of cells to decreased current was nonlinear for IgG-modified electrodes. The nonlinearity is confirmed by EIS measurements which showed highest impedance at 4 CFU/mL E. coli when impedance should be the lowest. FESEM images showed higher binding of cells when IgG is present compared to electrodes with reduced graphene oxide (rGO) alone. Electrodes with rGO alone show less attachment of E. coli, with EIS showing a linear calibration profile, while LSV shows not much difference in current values for all concentrations aside from the highest concentration. These results suggest that nonspecific binding can provide false signals in electrochemical measurements, and it is crucial to provide proper controls.

The aim of the study was to determine the possibility of suppression of the prostaglandin synthesis by new derivatives of N-phenylanthranilic acids; they inhibit the activity of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme using the method of a flexible molecular docking. For the docking studies the crystallographic structural models with high resolution from Protein Data Bank were used: mPGES-1 in the complex with glutathione (pdb code 4AL0). A flexible molecular docking was carried out using the Molecular Operating Environment (MOE) software package. According to the results of the docking studies four scoring functions were calculated (Affinity dG Scoring, Alpha HB Scoring, London dG Scoring, GBVI/WSA dG Scoring). The values of the scoring functions calculated indicate the thermodynamic probability and energy favorability of forming complexes between molecules of the substances under research and the specified receptor, in which arrangement of ligands in the active site of the receptor and residues of amino acids of side chains are of similar geometry and types of binding of the known inhibitors of mPGES-1 determined on the basis of the crystallographic studies.

Abstract: Background: chronotype is generally defined as the variability of the phase angle of en-trainment, while the latter reflects the relationship between the timing of a certain rhythm (e.g., sleep-wake cycle) and the timing of an external temporal cue. Individuals can be placed on a spectrum from "morning types" (M types), to "evening types" (E types). E-chronotype has been proposed as a transdiagnostic risk factor for psychiatric conditions and associated with psycho-pathological dimensions. Eveningness seems correlated with both suicidal ideation (SI) and suicidal behavioral (SB), through several possible mediating factors. Immunological alterations also have been linked to later chronotypes and SI/SB. Objective: This narrative review aims to summarize the evidence supporting the possible association between chronotypes and suicide, with the eventual mediating role of neuroinflammation and several psychopathological dimensions. Material and methods: A search of literature (2003-2023) was conducted, using various databases: PUBMED, EMBASE, Scopus, UpToDate, PsycINFO, Cochrane Library. English-language articles were col-lected and screened for eligibility. Results: Despite the apparent absence of a direct correlation between E-chronotype and suicidality, E-chronotype promotes a chain of effects that could be in-volved in an increased risk of SB, in which with neuroinflammation possibly play an intriguing role and some psychopathological dimensions may stand out.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically-based lipid disorder with the underestimated actual prevalence. In the recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. However, there is not enough data on their use in real-world clinical implementation. We studied the applicability of the most accessible biochemical algorithms to diagnose FD in clinical practice. We also investi-gated the prevalence of FD in one of the European regions of Russia based on a population sample. In this study there was detected a high prevalence of FD: 1 in 151. We demonstrated that the diagnostic algorithms of FD including a diagnostic apoB levels require correction, taking into account the characteristics of the distribution of apoB levels in the population. At the same time a triglycerides cutoff ≥1.5 mmol/L may be a useful tool in identifying subjects with FD. We also analyzed the presence and pathogenicity of APOE variants associated with the autosomal dominant FD in a large research sample.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

The popularity of electronic cigarettes in the United States and around the world has led to a startling rise in youth nicotine use. The Juul e-cigarette was introduced in the U.S. market in 2015 and had captured approximately 13% of the U.S. market by 2017. Unlike many other contemporary electronic cigarette companies, the founders behind the Juul® e-cigarette approached their product launch like a traditional high-tech start-up company, not like a tobacco company. This article presents a case study of Juul’s corporate and product development history in the context of US regulatory actions. The objective of this article is to demonstrate the value of government-curated archives as leading indicators which can (a) provide insight into emergent technologies and (b) inform emergent regulatory science research questions. A variety of sources were used to gather data about the Juul e-cigarette and the corporations that surround it. Sources included government agencies, published academic literature, non-profit organizations, corporate and retail websites, and the popular press. Data was disambiguated, authenticated, and categorized prior to being placed on a timeline of events. A timeline of four significant milestones, nineteen corporate filings and events, twelve US regulatory actions, sixty four patent applications, eighty seven trademark applications, twenty three design patents and thirty two utility patents related to Juul Labs and its associates is presented spanning the years 2004 thought 2020. This work demonstrates the probative value of findings from patent, trademark, and SEC filing literature in establishing a premise for emergent regulatory science research questions which may not yet be supported by traditional archival research literature. The methods presented here can be used to identify key aspects of emerging technologies before products actually enter the market, this shifting policy formulation and problem identification from a paradigm of being reactive in favor of becoming proactive. Such a proactive approach may permit anticipatory regulatory science research and ultimately shorten the elapsed time between market technology innovation and regulatory response.

There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in E. coli cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner. Cells expressing GST-hNdCTR1 protein demonstrated resistance to the metal treatments. These cells accumulated silver ions and formed nanoparticles that contained AgCl and Ag0. In this bacterial population, filamentous bacteria with length about 10 μm were often observed. The possibility for the fusion protein carrying extracellular metal binding motifs to integrate into the cell’s copper metabolism and its chelating properties are discussed.

A novel educational platform called Shared Modeling and Simulation Environment (SMSE) was initiated in the ERASMUS+ “CybPhys” project. It integrates the Jupyter platform, including Ju-pyter Notebooks, for e-learning in the STEM field. A novel platform enhances e-learning by combining Moodle with Jupyter's capabilities to create virtual labs. A survey was conducted in the spring of 2023 among bachelor and master students of Chernihiv National Polytechnic Uni-versity aimed to gather feedback from students using SMSE in their e-learning process. Two student groups were involved: one of them consisted of students using SMSE in both the autumn and spring semesters and another represented the students starting with SMSE in the spring se-mester. The survey based on the adjusted Technology Acceptance Model (TAM) was conducted to understand the acceptance of this e-learning approach. A comprehensive analysis of students’ answers based on the TAM approach revealed the inside of the process of transformation of stu-dents’ perceptions during the acquisition of the SMSE platform. Our research demonstrates that SMSE effectively merges Moodle's online learning capabilities with Jupyter notebooks, provid-ing a flexible and interactive learning experience for both in-class and remote students. It pro-vides a web-based, multifunctional e-learning environment that combines a variety of tools and technologies, giving students the possibility to be involved in all sorts of teaching activities, such as lectures, exercises, simulations, etc., through the use of one single online environment.

The COVID-19 pandemic was declared in March 2020 and is still ongoing. The course of the epidemic remains uncertain, and mutations in the coronavirus, as well as the emergence of new variants of concern, make it possible that there will be periodic surges in the number of cases. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the development of pan-coronavirus vaccines that stimulate the production of antibodies against conserved elements of the virus. Another approach could be the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. With a well-established safety profile and the ability to transform into vaccine candidates, probiotic bacteria have significant research potential. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters.

The pharmacokinetic profile of fat-soluble vitamins A, E, K1, and D3 co-administered with liquid paraffin or water in an experimental rat model was investigated. Animals received a solution of the four vitamins orally through a probe, followed 10 minutes later by the administration of either the liquid paraffin product dissolved in water (Emuliquen Simple®) or water (control). Vitamin formulations were 20, 50, 0.30 and 0.10 mg/kg for vitamins A, E, K1, and D3, respectively. Blood samples were collected before dosing and at 0.17, 1, 2, 4, 8, and 24 hours post-dosing. Vitamin concentrations were quantified by liquid chromatography coupled with mass spectrometry. No relevant differences in the absorption of vitamins in terms of AUC0-last (area under the curve up to the last measurable concentration) or Cmax in the absence or presence of co-administration of the liquid paraffin product were observed. The difference of these parameters between the treatment groups for all vitamins was in the range of bioequivalence (≤ 20%). The liquid paraffin-based laxative product did not interfere with the absorption of vitamins A, E, K1, and D3 that are ingested in the diet, which is clinically relevant due to the high prevalence of functional constipation in children and adults.

As digital technologies rapidly integrate into Health Professions Education (HPE), gaining a comprehensive understanding of cyberethics becomes crucial. This scoping review aimed to explore the pedagogy of cyberethics within HPE, with an emphasis on its definitions, conceptualizations, theoretical foundations, and interventions. Drawing from 37 documents spanning 2012-2022, primarily originating from the U.S. and encompassing both peer-reviewed and grey literature, the study highlighted a significant gap in the explicit definition and conceptualization of cyberethics. Additionally, the evident lack of specific theoretical frameworks in the majority of these documents could hamper the progression and replicability of research. Among the reviewed articles, only four introduced cyberethics educational interventions, indicating a substantial avenue for future research. While the study utilized comprehensive search methods, limitations such as language biases and the potential omission of pertinent documents were present. Future investigations should broaden the cyberethics discourse to encompass emerging technologies and their ethical implications within HPE. Crafting comprehensive, culturally sensitive, and inclusive guidelines is pivotal in nurturing ethical digital practices in the health care community.

The Internet of Things (IoT) was born from the fusion of virtual and physical space and became the initiator of many scientific fields. Economic sustainability is the key to further development and progress. Today, the need for electronic commerce has become an economic priority in the transition period between Industry 4.0 and Industry 5.0. Unlike mass production in Industry 4.0, customized production in Industry 5.0 should reach its true potential in vertically organized management and decision-making systems. The authors focused their research on e-commerce based on the three-level vertical IoT environment and the edge, fog, and cloud computing. The paper presents hands-on machine learning (ML) algorithms to facilitate the transition from a flat to a vertical e-commerce concept. The authors also propose practical ML algorithms for a few e-commerce types: consumer-consumer relationships and consumer-company-consumer relationships. These algorithms are mainly composed of convolution neural networks (CNN), natural language understanding (NLU) and sequential pattern mining (SPM), reinforcement learning (RL for agent training), algorithms for clicking on the item prediction, consumer behavior learning, etc. All presented concepts, algorithms, and models are described in detail.

This review is devoted to present the history of CARDIOSIM© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory system. The first version of CARDIOSIM© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on PC with disk operating system (MS-DOS) and was developed using the Turbo Basic language. The last version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce different pathophysiological conditions. The software simulator can reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It represents the whole circulation using a lumped-parameter model and enables the simulation of different cardiovascular conditions according to Starling’s law of the heart and a modified time-varying elastance model. Different mechanical ventilatory and circulatory devices have been implemented in the platform including thoracic artificial lung, ECMO, IABP, pulsatile and continuous right and left ventricular assist devices, biventricular pacemaker and biventricular assist devices. CARDIOSIM© is used in clinical and educational environment.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

The history of health records (later also called medical records), including ones regarding individual patients, is thousands of years old. It finds it roots in the first ancient civilisations. Up until the 19^th century the records’ purpose was mainly an educational one. In the 19^th and 20^th century they started becoming significant in other roles as well, including those not strictly limited to medicine. In particular, to account for medical procedures, insurance proceeds or legal action. Currently we are living in a revolutionary era when it comes to health records, in which their character has changed from a “paper-based” to an electronic one. This paper presents the development of health records from the ancient to modern times, mainly in Europe and North America. Other cultures and civilisations, including China and India, are not discussed. An analysis of available sources was conducted, inter alia digital versions of manuscripts up to hundreds of years old. The analysis was based on PubMed and Google Scholar (several key words, all the available sources). Sources published in non-international languages (e.g. Dutch) were also investigated. Overall, approximately 600 articles were analysed, 158 of which were used and cited in this paper. The conclusions drawn from the analysis are as follows: (1) Health records, priorly used mostly for educational purposes, for about 100 years now have acquired a fully formal status. (2) We are currently facing the most revolutionary changes regarding the transformation of paper-based records into electronic ones. (3) The consequences of this process include systematic applications of solutions within the area of e-health, which allow us to make medical services more flexible, improve the health of individual patients and entire populations and potentially limit expenditure. (4) In the light of the ongoing COVID-19 pandemic, introducing electronic health records could be beneficial in terms of limiting the potential sources of contamination (physical copies of health records), saving time and resources, and improving the network of communication between medical centres.

To delve into the structure-function relationship of transmembrane proteins (TMPs), robust protocols are needed to produce them in a pure, stable, and functional state. Among all hosts that express heterologous TMPs, E. coli has the lowest cost and fastest turnover. However, many of the expressed in E. coli TMPs are misfolded. Several strategies have been developed to either direct the foreign TMPs to E. coli’s membrane or retain them in a cytosolic soluble form to overcome this deficiency. Here, we summarize protein engineering methods to produce chimera constructs of the desired TMPs fused to either signal peptide or precursor maltose binding protein (pMBP) to direct the entire construct to the periplasm, therefore depositing the fused TMP in the plasma membrane. We further describe strategies to produce TMPs in soluble form by utilizing N-terminally fused MBP without signal peptide. Depending on its N- or C-terminus location, a fusion to apolipoprotein A-I can either direct the TMP to the membrane or shield the hydrophobic regions of the TMP, maintaining the soluble form. Strategies to produce G-protein coupled receptors, TMPs of Mycobacterium tuberculosis, HIV-1 Vpu, and other TMPs are discussed. This knowledge could increase the scope of TMPs’ expression in E. coli.

This study aimed to assess the microbiological quality of set of fruits and vegetables sold on stalls in the streets and open markets of Dakar, the capital city of Senegal. Samples purchased in seven sites were analyzed to isolate E. coli, Salmonella spp. and Vibrio spp. Some primary samples with a positive microbiological culture were subjected to DNA extraction and subsequent metagenomic analysis. A total of 240 fresh fruit and vegetable samples were collected including lettuce (n=40), tomatoes (n=40), mango slices (n=40), onion slices (n=40), mint leaves (n=40), strawberries and grapes (respectively n=20). Of these samples, 50.83% (122/240) and 60.41% (145/240) was contaminated with Escherichia coli and Vibrio spp. respectively, while Salmonella was not isolated in any product. Levels of contamination with both E. coli (1.3 103 to 6 106 CFU/g) and Vibrio spp. (4.55 102 to 8.73 106 CFU/g) were significantly above the thresholds acceptable for human consumption. The most contaminated samples were lettuce with a prevalence of 98% (39/40) for E. coli and for Vibrio spp. followed by mint leaves with 100% (40/40) and 93% (37/40) of the samples containing for E. coli and Vibrio spp. respectively. Out of 46 samples sequenced, metagenomic analysis revealed high contamination rates for E. coli, Vibrio spp. and Salmonella spp. with 100%, 67.39% and 93.47% of prevalence respectively. On the other hand, the alpha diversity analysis shows a high bacterial diversity in lettuce and mint leaf samples while beta diversity analysis highlighted the presence of two major clusters. Our results stress the need of a surveillance system that extends this investigation to a national scale while increasing the number of sampling sites and products analyzed.

The purpose of this research was to analyze the moderating effect of clean energy innovation on the relationship between corporate carbon footprint and corporate profits in those industrial sectors associated with high demand for fossil fuels in which it is "hard to abate" CO₂e emissions. It used a longitudinal research design, in particular a panel study under a structural equation modeling (SEM) approach, based on partial least squares. For the longitudinal moderation analysis, this research employed the Bayesian method by defining a multiple-indicator latent growth curve model (B-LGC model). A global sample was used consisting of 7,827 firm-year observations between 2015 and 2021 corresponding to 167 international firms. The results revealed a very significant impact of the corporate carbon footprint on corporate profits. Likewise, the results showed that innovations in clean energy, when measured as the consumption of renewable energy, positively moderates the relationship between the greenhouse gas emissions from the value chain associated with Scope 3 of the Greenhouse Gas (GHG) Protocol, and the gross profit margin obtained. Besides the academic contribution represented by the moderating effect of clean energy innovation, these findings imply that a more detailed understanding of the emissions of the entire value chain (Scope 3 CO₂e) by executives and managers of high emitting CO₂e companies represents an effective mechanism to obtain higher profits, create competitive advantages and, at the same time, achieve a net zero emissions strategy. More importantly, public policy makers will be able to use these results to revise CO₂e-related policies paying more attention to the Scope 3 CO₂e emissions produced by these companies, to formulate regulatory and control mechanisms that stimulate clean energy innovation.

Geomagnetic induced current (GIC) is a ground end manifestation associated with the space weather perturbations that should be greatly taken into account by the society. Although the GICs implication to the power system is not regular, it can cause large scale of system failure. In equatorial, the power system is considered safe since the most intense of geomagnetic storm happened in high latitude. However, the internal damage due to GICs which finally led to the South African power system failure has totally changed the normal perception. Therefore, a preliminary investigation on the GICs activity in equatorial region is performed to understand the space weather impact to the power system. Time derivative of the horizontal magnetic field component (dB/dt) is done to indicate the GICs activity value based on Faraday’s law. All the reported power failures are compiled to produce the threshold value of dB/dt, which possibly cause the harmful effect to the system. Then, dB/dt analysis is extended to show the pattern of GICs activity in function of magnetic latitude and local time. The results reveal that power network in equatorial region has possibly suffered by GIC. Plus, high number of intense GIC activity in this region occurred during dayside.

Genetic variations at the Apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) loci have been implicated in multiple neurogenerative diseases, but their exact molecular mechanisms are unclear. In this study we performed transcript level linear modelling using the blood whole transcriptome data and genotypes of the 570 subjects in the Parkinson’s progression markers initiative (PPMI) cohort. ApoE, MAPT haplotypes and two SNPs at the SNCA locus (rs356181, rs3910105) were used to detect expression quantitative trait loci eQTLs associated with the transcriptome and differential usage of transcript isoforms. As a result, we identified 151 genes associated with the genotypic variations, 29 cis and 122 trans eQTL positions. Profound effect with genome-wide significance of ApoE e4 haplotype on the expression of TOMM40 transcripts was identified. This finding potentially explain in part the frequently established genetic association with the APOE e4 haplotypes in neurodegenerative diseases. Moreover, MAPT haplotypes had significant differential impact on 23 transcripts from the 17q21.31 and 17q24.1 loci. MAPT haplotypes had also the largest (256) and smallest (-178) effect sizes measured as beta values on two different transcripts from the same gene (LRRC37A2). Intronic SNP in the SNCA gene, rs3910105, differentially induces expression of three SNCA isoforms. In conclusion, this study established clear association between well-known haplotypic variance and transcript specific regulation in the blood. APOE e4 and MAPT H1/H2 haplotypic variants are associated with the expression of several genes related to the neurodegeneration.

This paper presents an overview of the smart electro-clothing systems (SeCSs) targeted at health monitoring, sports benefits, fitness tracking, and social activities. Technical features of the available SeCSs, covering both textile and electronic components, are thoroughly discussed and their applications in the industry and research purposes have been highlighted. In addition, it also presents the developments in the associated areas of wearable sensor systems and textile-based dry sensors. As it became evident during the literature research, such a review on SeCSs covering all relevant issues has not been presented before. This paper will be particularly helpful for new generation researchers investigating the design, development, function and comforts of the sensor integrated clothing materials.

Given the rise in the number of cases and their recurrences, Urinary Tract Infections (UTI) are one of the major burdens on public healthcare worldwide. Rapid, inexpensive and selective detection of Uropathogenic E. coli (UPEC), a major contributor to UTIs, is the need of the hour for effective treatment, given the rise of antibiotic-resistant bacteria due to improper diagnosis. Here we present a rapid, real-time, selective and label-free detection of UPEC using an integrated sensing platform based on Crossed Surface Relief Gratings (CSRGs) as nanoplasmonic sensors. Detection is achieved due to the unique Surface Plasmon Resonance (SPR)-based light energy exchange attributed to the CSRGs, allowing real-time sensing in a very narrow bandwidth of the incident light to pass where the SPR energy conversion occurs. The sensing ability of the platform is experimentally demonstrated by the detection of bulk Refractive Index (RI) changes, with a bulk sensitivity of 382.2 nm/RIU and a resolution in the order of 10-6 RIU. We demonstrate selective capture and detection of clinical concentration of UPEC, as opposed to other gram-negative bacteria, in real-time, a first for CSRGs. This work is particularly important for effective treatment of UTIs, allowing point-of-care diagnosis for economically disadvantaged regions around the world.

The arrival of new developments in the field of power electronics circuit’s applications in power systems builds new control strategy to improve voltage quality for power grid by overcome interruptions. Wind energy resources are unconventional resources and get advanced problems to power grid when it is connected. Uncertainty of load sharing, peak energy management, climatic conditions, wind velocity and wind energy injected into power grid leads many of power quality problems on power grid based on the existing guidelines specified in IEC-61400 standard. This system plans efficient operation of DFIG to eliminate the voltage collapse and mismatch frequency to power grid. The DFIG connected diode rectifier and rotor side converter wind generator works as an Efficient Static Synchronous Compensator (E-SATCOM) for supplying the demand of reactive power for power grid to mitigate PQ problems. The benefit of using a combined controller was verified by simulink/Matlab and its simulated results used Doubly Fed Induction Generator (DFIG), wind Turbine. This simulation results gives good quality transient and stable state response to manage and support reactive power for both symmetrical and unsymmetrical faults in connection of grid codes to provide continuous quality of power supply, multiple wind generators are required for 140 bus power grid.

The greenhouse gases and air pollution generated by extensive energy use have exacerbated climate change. An electric-bus (e-bus) transportation system favors reducing pollution and carbon emissions. This study analyzed the minimization of construction costs for an all battery-swapping public e-bus transportation system. A simulation was conducted according to existing timetables and routes. Daytime charging was incorporated during the hours of operation; the two parameters of the daytime charging scheme were the residual battery capacity and battery-charging energy during various intervals of daytime peak electricity hours. The parameters were optimized using three algorithms: particle swarm optimization (PSO), a genetic algorithm (GA), and a PSO–GA. This study observed the effects of optimization on cost changes (e.g., number of e-buses, on-board battery capacity, number of extra batteries, charging facilities, and energy consumption) and compared the plug-in and battery-swapping e-bus systems. The results revealed that daytime charging can reduce the construction costs of both systems. In contrast to the other two algorithms, the PSO–GA yielded the most favorable optimization results for the charging scheme. Finally, according to the cases investigated and the parameters of this study, the construction cost of the plug-in e-bus system was lower than that of the battery-swapping e-bus system.

Artificial Intelligence (AI) and Deep Reinforcement Learning (DRL) have revolutionised e-learning by creating personalised, adaptive, and secure environments. However, challenges such as privacy, bias, and data limitations persist. E-FedCloud aims to address these issues by providing more agile, personalised, and secure e-learning experiences. This study introduces E-FedCloud, an AI-assisted adaptive e-learning system that automates personalised recommendations and tracking, thereby enhancing student performance. It employs federated learning-based authentication to ensure secure and private access for both course instructors and students. Intelligent Software Agents (ISAs) evaluate weekly student engagement using the Shannon Entropy method, classifying students into either engaged or not-engaged clusters. E-FedCloud utilises weekly engagement status, demographic information, and an innovative DRL-based early warning system, specifically ID2QN, to predict the performance of not-engaged students. Based on these predictions, the system categorises students into three groups: risk of dropping out, risk of scoring lower in the final exam, and risk of failing the end exam. It employs a multi-disciplinary ontology graph and an attention-based capsule network for automated, personalised recommendations. The system also integrates performance tracking to enhance student engagement. Data is securely stored on a blockchain using the LWEA encryption method.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. Similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with peptidoglycan maximally hydrolyzed had a greater protectivity compared to BGs with preserved peptidoglycan skeleton.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

This study investigates the factors influencing the choice of online and offline shopping trips and their impacts on urban transportation, environment, and economy in Tehran, Iran. A questionnaire survey was conducted to collect data from 1,000 active e-commerce users who made successful orders in both online and offline services in the last 20 days of 2021 in areas 2 and 5 of Tehran. A deep neural network model was developed to estimate the type of shopping trip based on 10 indicators, such as age, gender, car ownership, delivery cost, product price, etc. The performance of the model was compared with three other algorithms: MLP, decision tree, and KNN. The results showed that the deep neural network model had the highest accuracy of 95.63%. The most important factors affecting the choice of shopping trips were delivery cost, delivery time, and product price. This study provides insights for transportation planners, e-commerce managers, and policymakers to design effective strategies for reducing transportation costs, pollutant emissions, urban traffic, and increasing user satisfaction and sustainable development.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values &lt; 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

Myr47 lipopeptide consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2-48 peptide) is a commercialized effective anti-HBV drug, preventing the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, of which the activity requires both N-myristoylation residue and specific amino acid sequence. Meanwhile, we recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression (Somiya; et al. Virology 2016, 497, 23–32). In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner whereas in an amino acid sequence-independent manner. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, N-myristoyl residue of lipopeptides generally could interfere the LPs/HBsAg-ApoE3 complex formation, thereby reducing the cellular uptake of LPs/HBsAg. When lipid nanoparticles are used as a DDS (drug delivery system) nanocarrier, the surface modification with lipopeptides may be a new method to inhibit unwanted cellular uptake of DDS nanocarriers by non-target cells.

An accurate radiative transfer model (RTM) is essential for the retrieval of soil moisture (SM) from microwave remote sensing data, such as the passive microwave measurements from the Soil Moisture Active Passive (SMAP) mission. This mission delivers soil moisture products based upon L-band brightness temperature data, via retrieval algorithms for surface and root-zone soil moisture, the latter is retrieved using data assimilation and model support. We found that the RTM based on the tau-omega (?-ω) model, can suffer from significant errors over croplands (in average between -9.4K and + 12.0K for Single Channel Algorithm SCA; -8K and + 9.7K for Dual-Channel Algorithm DCA) if the vegetation scattering albedo (omega) is treated as a constant and the temporal variations are not accounted. In order to reduce this uncertainty, we propose a time-varying parameterization of omega for the widely established zeroth order radiative transfer ?-ω model. The main assumption is that omega can be expressed by a functional relationship between vegetation optical depth (tau) and the Green Vegetation Fraction (GVF). The validation was performed from 14 May to 13 December 2015 over 61 Climate Reference Network sites (SCRN) classified as croplands. The application of the proposed time-varying vegetation scattering albedo results in a consistent improvement for the unbiased root mean square error of 16% for SCA and 15% for DCA. The reduction for positive and negative biases was 45% and 5% for SCA and 26% and 12% for DCA, respectively. This indicates that vegetation dynamics on croplands are better represented by a time-dynamic single scattering albedo.

This study examines the role of using algorithmic HRM to make strategic decisions pertaining to HR activities in organizations. The study develops a scale to measure algorithmic HRM usage in its first phase, and in the second phase, it finds that algorithmic HRM having significant impact on the strategic HR decision making that helps and enables organization in creating the competitive advantage. Utilizing the author’s LinkedIn profile, 234 final participants considered for this research. Collected data analyzed by applying PLS SEM. It evaluates the mediation role of the HR strategic decision making, and the HR digital maturity as a moderator in seeing the impact of algorithmic HRM on the competitive advantage of the firm. The study finds a strong relationship between the algorithmic HRM usage and competitive advantage, a significant relationship between algorithmic HRM usage and the strategic HR decision making, and lastly, a significant relationship between strategic HR decision making and the competitive advantage. The moderating role of HR digital maturity was found to be insignificant in this research which paves the way for further research. This research, the model, and its findings contribute to the theory and implicate the practicality of algorithmic HRM. It's one of few papers that address the algorithmic HRM usage in the transitioning economy like Saudi Arabia.

Historically, viral hepatitis is a considerable public health problem in Central Asian countries, which may have worsened after dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n=1075). Participants, children and adults, were recruited from an outpatient clinic. Data were collected during face-to-face interviews. A blood sample (6 ml) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D and E). Poststratification weighting was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval: 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg positive participants, five (15%) were anti-HDV positive. Our study confirms that Kyrgyzstan remains a high endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here we study in silico and in vitro the structure of the protein, its interaction with RAE1, and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the membranes of the endoplasmic reticulum, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA-DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenesis of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

Background: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8±8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (P<0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. These observations contribute to the development of a population recovery strategy after the episodes of COVID-19.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

Synthetic fuels play an important role in the defossilization of future aviation transport. To reduce the ecological impact of remote airports due to long range transportation of kerosene, a decentralized on-site-production of synthetic paraffinic kerosene is applicable, preferably as near-drop-in fuel or alternatively as blend. One possible solution for such a production of synthetic kerosene is the Power-to-Liquid process. The basic development of a simplified plant layout addressing the specific challenges of a decentralized kerosene production which differ from most current approaches for infrastructural well-connected regions is described. The decisive influence of the Fischer-Tropsch synthesis on the PtL process is shown by means of a steady-state reactor model which was developed in Python and serves as basis for further development of a modular environment able to represent entire process chains. The reactor model is based on reaction kinetics according current literature. The effects of adjustments of the main operation parameters on the reactor behavior are evaluated and the impacts on up- and downstream processes are described. The results prove the governing influence of the Fischer-Tropsch reactor on the PtL process and show its flexibility regarding the desired product fraction output, which makes it an appropriate solution for a decentralized kerosene production.

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

The electronic cigarette or e-cigarette is the new alternative method to deliver nicotine. In 2007, the United States introduced vaping devices on the market. Due to their attractive taste and lack of adverse effects, these vaping devices have gained popularity among youth and adults. However, there has been increasing evidence that vaping can cause severe lung injury, and these devices release toxic chemicals into the body. E-cigarettes are recognized as a global threat to public health. Nicotine, the most prevalent chemical in vaping devices, is associated with neurological problems and cognitive decline. Long-term use of e-cigarettes can cause adverse health problems, including respiratory illnesses, asthma, bronchitis, and lung inflammation. In 2019, the Centers for Disease Control and Prevention (CDC) officially declared vaping-associated illness EVALI (e-cigarette or Vaping Product Associated Lung Injury). The US Surgeon General published an alarm in December 2016 that e-cigarette consumption among adolescents and teens in the US is a "major public health concern" and that more young people are now vaping than smoking traditional cigarettes and cigars. Since its commercial introduction in 2003, modern electronic cigarettes (or E-cigarette s) have become increasingly popular with smokers, non-smokers, and those who used to smoke who have switched to them. With such a rise in consumption, people are becoming more aware of the irritating, harmful, and perhaps cancer-causing effects on the lungs. (Chadi et al., 2019; Dinardo & Rome, 2019; Lyzwinski et al., 2022; Marrocco et al., 2022; O’Callaghan et al., 2022)

Currently, there is increasing industrial demand for rare earth elements (REE) as these elements are now integral to the manufacture of many carbon-neutral technologies. The depleting REE ores and increasing mining costs are prompting to look for alternative sources for these valuable metals, particularly from waste streams. Although REE concentrations in most of the alternate resources are lower than current REE ores, some sources such as marine sediments, coal ash, and industrial wastes like red mud are looking promising with significant concentrations of REE in them. This review focuses on the alternative resources for REE such as ocean bottom sediments, continental shelf sediments, river sediments, stream sediments, lake sediments, phosphorites deposits, industrial waste products like red mud, and phosphogypsum, coal, coal fly ash, and related materials, waste rock sources from old and closed mines, acid mine drainage, and recycling of e-waste. Possible future Moon exploration and mining for REE and other valuable minerals are also discussed. It is evident that REE extractions from both primary and secondary ores alone are not adequate to meet the current demand, and sustainable REE recovery from the alternative resources described here is also necessary to meet the growing REE demand. An attempt is made to identify the potential of these alternative resources and sustainability challenges, benefits, and possible environmental hazards to meet the growing challenges in meeting the future REE requirements.

To enable the deployment of battery-electric vehicles (BEV) as passenger cars in the private transport sector, a suitable charging infrastructure is crucial. In this paper a methodology for efficient spatial distribution of charging infrastructure is evaluated by investigating a scenario with a market penetration of BEVs of 100 percent (around 1.3 million vehicles). It aims towards the development of various charging infrastructure scenarios - including public and private charging - which are suitable to cover the charging demand. Therefore, these scenarios are investigated in detail with focus on number of public charging points, their spatial distribution, the available charging power and the necessary capital costs. For the creation of those charging infrastructure scenarios a placement model is developed. It uses the data of a MATSim (Multi-Agent Transport Simulation) traffic simulation of the metropolitan area of Berlin to evaluate and optimize different distributions of charging infrastructure. The model uses a genetic algorithm and the principle of multi-objective optimization. The capital cost of the charging points and the mean detour car drivers must cover additionally are used as optimization criteria. Using these criteria should lead to cost efficient infrastructure solutions which provide high usability at the same time. The main advantage of the method selected is that multiple optimal solutions with different characteristics can be found and suitable solutions can be selected by using other criteria subsequently. The optimized charging infrastructure solutions show capital costs between 624 and 2950 million euro. Users must cover an additionally mean detour of 254m to 590m per charging process to reach an available charging point. According to the results a suitable ratio between charging points and vehicles is between 11:1 and 5:1. A share of fast charging infrastructure (&gt;50kW) of less than ten percent seems to be sufficient, if it is situated at main traffic routes and highly frequented places.

Online and offline shopping trip have different impacts on various aspects of urban life, such as e-commerce, transportation systems, and sustainability. Therefore, it is important to evaluate the factors that influence their choices. We use a hybrid machine learning model that combines a gray wolf optimization algorithm and a deep convolutional neural network to estimate shopping trip based on a survey of 1,000 active e-commerce users who made successful orders in both online and offline services in the last 20 days of 2021 in areas 2 and 5 of Tehran. The gray wolf optimization algorithm performs feature selection and hyperparameter tuning for the deep convolutional neural network, which is a powerful deep learning model for image recognition and classification. The results show that our model achieves an accuracy of 97.81% with an MSE of 0.325 by selecting seven out of ten features. The most important features are delivery cost, delivery time, product price, car ownership. In addition, comparing the performance of the proposed method with other methods showed that the proposed algorithm with an accuracy of 97.81%, the accuracies of the single deep learning model, MLP neural network, decision tree, and KNN models were 95.63%, 90.0%, 86.49%, and 80.16%, respectively.

Electric moped scooter sharing services have recently experienced strong growth rates, particularly in Europe. Due to their compactness, environmental-friendliness and convenience, shared e-mopeds are suitable modes of transport in urban mobility to help reduce the environmental impact. However, its traffic-related, economic and environmental effects are merely represented in academic research. We used passenger car traffic data in Berlin generated by the multi-agent transport simulation framework MATSim to develop a python-based simulation, resembling an e-moped sharing system. Based on the results, a total cost of ownership and a life cycle assessment for fleet sizes of 2,500, 10,000 and 50,000 vehicles were conducted. The results indicate that a substantial part of all passenger car trips in Berlin can be substituted. The larger the fleet, the more and longer trips are replaced. Simultaneously, the efficiency in terms of fleet utilization decreases. The scenario with 10,000 e-mopeds offers the lowest total distance-based costs for sharing operators, whereas a fleet consisting of 2,500 vehicles exhibits the lowest environmental emissions per kilometer driven over the expected lifespan of a shared e-moped. Based on the renewable energy potential for 2050 forecasted by the German Federal Environment Agency, a significant overall decline in environmental impacts can be achieved.

Various factors, such as uncertainty of component parameters and uncertainty of sensor meas-urement values, contribute to the difficulty of fault detection in the landing gear retrac-tion/extension hydraulic system. In this paper, we introduce linear fractional transformation technology and uncertainty analysis theory for the construction of the diagnostic bond graph of the landing gear retraction/extension hydraulic system. In this way, interval analytical redundancy relations and fault signature matrix can be derived. Using the fault signature matrix, existing faults of the system can be preliminarily detected and isolated. Additionally, interval analytical re-dundancy relations can be used to detect system faults in detail, and cases analysis can be carried out to determine if the actuator is externally or internally leaky, and if the landing gear selector valve is reversing stuck. Compared to the traditional analytical redundancy relations, this method takes into account the negative factors of uncertainty; and compared to the traditional absolute diagnostic threshold, the interval diagnostic threshold is more accurate and sensitive.

: E-commerce sales surge represents a huge challenge for urban freight transport. Parcel lockers constitute a valid solution for addressing the challenges home deliveries imply. In fact, eliminating courier-consumer contact (also relevant for health-related issues, as made evident by COVID19 pandemic) and delivering in few predefined places might help coping with missed deliveries substantially. Furthermore, this option enables consolidated shipping and reducing delivery trip costs. This paper analyses and compares consumers’ preferences for alternative collection strategies. It investigates home delivery vs parcel locker use and forecasts their future market shares. This is performed based on both customers’ socio-economic variables and attributes characterising these alternative logistic fulfilment strategies. The case study considered rests upon a stated preference survey deployed in the city of Rome. The investigation specifically targets young people (i.e., population under 30 years) since they represent early adopters. Discrete choice models allow both quantifying the monetary value of parcel lockers attributes (i.e., willingness to pay measures) and estimating the potential demand for this innovative delivery scheme. Results show that distance and accessibility are the main choice determinants. Furthermore, there is an overall high propensity to adopt parcel lockers. This research can support policymakers when implementing such solutions.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

The core motivation for this study emanates from Voronin S.'s seminal work on the universality of the zeta function. This universality positions the zeta function as a pivotal element in the conceptual framework of global artificial intelligence, suggesting its potential as a foundational component. A critical barrier to harnessing this promising universality has been the absence of efficient algorithms capable of actualizing this concept.

Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

Abstract:The digital landscape is rapidly reshaping under the influence of AI-powered cloud-based e-commerce platforms (PCEPs). These platforms leverage the transformative power of AI to personalize customer experiences, optimize pricing strategies, enhance security, and streamline operations, offering businesses a significant competitive edge. However, challenges surrounding data privacy, algorithmic bias, and potential job displacement raise crucial ethical questions regarding widespread AI adoption in e-commerce.This study delves into the untapped potential and ethical considerations of PCEPs, distinguishing itself by proposing practical strategies for responsible development and ethical implementation.Objectives: Investigate the transformative potential of PCEPs: Personalized product recommendations:Analyze effectiveness and potential bias. Dynamic pricing strategies:Explore impact on consumer fairness and market stability. Enhanced fraud detection:Evaluate accuracy and privacy implications. Optimized supply chain management:Assess efficiency gains and job displacement risks. Critically analyze the ethical considerations of AI in e-commerce: Data privacy:Assess current practices and develop mitigation strategies. Algorithmic bias:Identify potential sources and propose solutions for fairer decision-making. Job displacement:Evaluate impacts and propose reskilling initiatives. Propose comprehensive and practical strategies for responsible PCEP development and implementation: Transparency:Enhance user awareness and control over data usage. Fairness:Design AI systems to mitigate bias and uphold consumer rights. Accountability:Establish clear guidelines and oversight mechanisms for ethical AI development.Conclusion: While PCEPs offer a plethora of transformative benefits, their ethical implementation is paramount. By adhering to principles of transparency, fairness, and accountability, businesses can unlock the full potential of PCEPs while minimizing potential risks and shaping the future of online commerce in a sustainable and equitable manner

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

Abstract:Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass