Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

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

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

The issue of women’s participation in top management and boardroom positions has received increasing attention in the academic literature and the press. However, the pace of advancement for women managers and directors continues to be slow and uneven. The novel framework of this study organizes the factors at the individual, organizational and public policy level that affect both career persistence and the advancement of women in top management positions; namely, factors affecting 1) career persistence (staying at the organization) and 2) career advancement or mobility (getting promoted within the organization). In the study location, Chile, only 32 percent of women “persist”, or have a career without interruptions, mainly due to issues with work–family integration and organizational environments with opaque and challenging working conditions. Women who “advanced” in their professional careers represent 30 percent of high management positions in the public sector and 18 percent in the private sector. Only 3 percent of general managers in Chile are women. Women in Chile have limited access and are still not integrated into business power networks. Our findings will enlighten business leaders and public policy-makers interested in designing organizations that retain and promote talented women in top positions.

Women's leadership continues to be a critical issue in today's society. Women face significant challenges in leadership, including limited representation in high-level positions and persistent gender-based discrimination. Many factors, including personal experiences, education, work experiences, and the influence of role models, influence women's leadership paths. This study explores how historical and contemporary role models help guide women's leadership choices. Specifically, we seek to understand the role of historical and contemporary role models in shaping women's perceptions of leadership and influencing their career aspirations.The study uses a qualitative research design to explore the experiences of women leaders in different industries. The participants were selected using purposive sampling, and data were collected through semi-structured interviews. Thematic analysis was used to identify patterns in the data, and the results were presented using descriptive statistics and qualitative data analysis.The study findings reveal that historical and contemporary role models significantly shape women's perceptions of leadership and influence their career aspirations. Women who have had access to role models in their personal lives or through media exposure are more confident in their ability to lead. They are more likely to pursue leadership positions. Historical role models provide women with tangible examples of what is possible regardingwomen's leadership. Studying role models from diverse backgrounds is essential in inspiring women from diverse backgrounds to pursue leadership roles.The study findings have significant implications for women's leadership development. They suggest efforts to increase the representation of women in leadership positions should focus on providing access to diverse role models. Additionally, the study highlights the importance of media representation of women leaders, as exposure to role models through media can help overcome barriers to access to role models in personal and professional networks.In conclusion, the study provides important insights into the influence of historical and contemporary role models on women's leadership paths. The study underscores the importance of role models in inspiring and guiding women's leadership journeys and the need for diverse and inclusive representation of women leaders in media and personal and professional networks. The findings provide practical recommendations for women's leadership development initiatives and future research.

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

Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of the ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analysis of randomized controlled trials (RCTs), assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identify, analyzed in terms of safety/efficacy ratio and of risk of bias, and graded using Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In IVF population not at high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of GnRH antagonist may reduce the OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have shown to be promising.

The environmental exposure of human in the daily and occupational activities to plasticizers may adversely affect human health, and thus represents a global issue. The altered expression of MicroRNAs (miRNAs) exerts an important pathogenic role linked also to the exposure to plasticizers. This systematic review summarizes the recent findings showing modified ex-pression of miRNAs in cancer due to plasticizers exposures. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review of the past ten years, focusing on the relationship between plasticizer exposures and expression of miRNAs cancer. Starting by 535 records, 17 articles were included. Results support the hypothesis that exposure to plasticizers cause changes or deregulation of a number of oncogenic miRNAs and showed that plasticizers interaction with several redundant miRNAs, such as let-7f, let-7g, miR-125b, miR-134, miR-146a, miR-22; miR-192, miR-222, miR-26a, miR-26b, miR-27b, miR-296, miR-324, miR-335, miR-122, miR-23b, miR-200, miR-29a and miR-21, might induce deep alterations. These genotoxic and oncogenic responses can eventually lead to abnormal cell signaling pathways and metabolisms that participate in many overlapped cellular processes, and miRNA level changes can be a useful tool for the toxicological assessment of environmental pollutants, including plastic additives and plasticizers

Inorganic nanoparticles are utilized for therapeutic, diagnostic, or in combination, theranostic purposes. The latter involves simultaneous sensing, imaging, or tracking of drug delivery. Furthermore, these nanoparticles can differ in their morphologies, which affect outcomes such as the effectiveness of hyperthermia, induction, drug loading, circulation time by escaping the body's immune system, imaging modality clarity, and biosensing. However, design of these theranostics is limited by the lack of a method to predict their therapeutic efficacy. Herein, we report a simple and novel computational approach via algebraic and geometric calculations of surface area (SA) to volume (V) ratios (SA:V) which can help predict the efficacy of the inorganic nanoparticles of the investigated morphologies. The approach comprises a coding platform for the program and uses Python 3 on a Windows 10 operating system. Analyses of 29 polyhedral morphologies that inorganic nanoparticles could assume ex silico showed that only particular concave and convex morphologies in this size regime are more productive over the standard sizes as well as a few noted in literature for baseline comparison. Our results provide a method that can aid in predicting the efficacy of inorganic nanoparticles with certain morphology giving rise to their fundamental basis and eventual implementation ex silico.

Knowledge of permafrost’s ice and unfrozen water content is critical for predicting the permafrost behavior during ice–water–ice transition. This is especially relevant when ice and permafrost are melting in many regions under the influence of global warming. It is well-known that only a part of the formation's pore water turns into ice at 0 ^oC. After the further lowering the temperature, the water phase transition continues, but at gradually decreasing rates. Thus, the porous space is filled with ice and unfrozen water. The laboratory data show that frozen formations' mechanical, thermal, and rheological properties strongly depend on the moisture content. Hence, porosity and temperature are essential parameters of permafrost. In this paper, it is shown how, and by combining research in three fields: (1) geophysical exploration, (2) numerical modeling, and (3) temperature logging, it is possible to estimate in-situ the porosity of permafrost. To demonstrate the procedure, five examples of numerical modeling (where all input parameters are specified) are given. This investigation is the first attempt to analyze the permafrost’s porosity in situ quantitively.

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

The ability to predict the skin sensitization potential of small organic molecules is of high importance to the development and safe application of cosmetics, drugs and pesticides. One of the most widely accepted methods for predicting this hazard is the rodent local lymph node assay (LLNA). The goal of this work was to develop in silico models for the prediction of the skin sensitization potential of small molecules that go beyond the state of the art, with larger LLNA data sets and, most importantly, a robust and intuitive definition of the applicability domain, paired with additional indicators of the reliability of predictions. We explored a large variety of molecular descriptors and fingerprints in combination with random forest and support vector machine classifiers. The most suitable models were tested on holdout data, on which they yielded competitive performance (Matthews correlation coefficients up to 0.52; accuracies up to 0.76; areas under the receiver operating characteristic curves up to 0.83). The most favorable models are available via a public web service at https://nerdd.zbh.uni-hamburg.de/skinDoctor/ that, in addition to predictions, provides assessments of the applicability domain and indicators of the reliability of the individual predictions.

Chemical exposures from diverse sources merge on a limited number of molecular pathways described as toxicity pathways. Changes in the same set of molecular pathways in different cell and tissue types may generate seemingly unrelated health conditions. Today, no approaches are available to predict in an unbiased way sensitivities of different disease states and their combinations to multichemical exposures across the exposome. We propose an inductive in-silico workflow where sensitivities of genes to chemical exposures are identified based on the overlap of existing genomic datasets, and data on sensitivities of individual genes is further used to sequentially derive predictions on sensitivities of molecular pathways, disease states, and groups of disease states (syndromes). Our analysis predicts that conditions representing the most significant public health problems are among the most sensitive to cumulative chemical exposures. These conditions include six leading types of cancer in the world (prostatic, breast, stomach, lung, colorectal neoplasms, and hepatocellular carcinoma), obesity, type 2 diabetes, non-alcoholic fatty liver disease, autistic disorder, Alzheimer's disease, hypertension, heart failure, brain and myocardial ischemia, and myocardial infarction. Overall, our predictions suggest that environmental risk factors may be underestimated for the most significant public health problems.

We estimate the determinants of Emissions-COE in the context of Environmental, Social and Governance-ESG model at world level. We use data of the World Bank for 193 countries in the period 2011-2020. We found that the level of COE is positively associated, among others to “Methane Emissions”, “Research and Development Expenditures”, and negatively associated among others to “Renewable Energy Consumption” and “Mean Drought Index”. Furthermore, we have applied a cluster analysis with the k-Means algorithm optimized with the Elbow Method and we find the presence of four cluster. Finally, we apply eight machine-learning algorithms for the prediction of the future value of COE and we find that the Artificial Neural Network-ANN algorithm is the best predictor. The ANN predicts a reduction in the level of COE equal to 5.69% on average for the analysed countries.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

In this article, we estimate the value of Government Expenditure on Education-GEE in the context of Environmental, Social and Governance-ESG dataset of the World Bank. We use data from 193 countries in the period 2011-2020. We use Panel Data with Fixed Effects, Panel Data with Random Effects, Pooled Ordinary Least Squares-OLS, and Weighted Least Squares-WLS. Our results show that the value of GEE is positively associated among others to “Case of Death, by communicable disease and maternal, prenatal and nutrition conditions”, and “Unemployment”, and negatively associated among others to “Hospital Beds” and “Government Effectiveness”. Furthermore, we apply the k-Means algorithm optimized with the Elbow Method and we find the presence of four clusters. Finally, we confront eight machine learning algorithms for the prediction of the future value of GEE. We found that the Polynomial Regression is the best predictive algorithm. The Polynomial Regression predicts an increase in GEE of 7.09% on average for the analysed countries.

In this article, we estimate the role of Political Stability and Absence of Violence and Terrorism-PS in the context of Environmental, Social and Governance-ESG data at world level. We analyse data from 193 countries in the period 2011-2020. We apply Panel Data with Fixed Effects, Panel Data with Random Effects and Pooled Ordinary Least Square-OLS. We found that PS is positively associated, among others, to Population Density and Government Effectiveness, and negatively associated, among others, to Research and Development Expenditure and Maximum 5-day Rainfall. Furthermore, we apply the k-Means algorithm optimized with the application of the Elbow Method and we find the presence of four clusters. Finally, we propose a confrontation among eight different machine-learning algorithms for the prediction of PS and we find that the Polynomial Regression shows the higher performance. The Polynomial Regression predicts an increase in the level of PS of 0.25% on average for the analysed countries.

Nowadays, the high demand for healthy foods and sustainable products, has led the food industry to explore innovative food technologies, such as fortification with bioactive compounds like antioxidants and polyphenols, that may be sourced from herbs or by-products. The aim of the present study was to explore the enrichment of refined olive oils with natural bioactive compounds such as the herbs rosemary (salvia rosmarinus), basil (ocimum basil), sage (salvia officinalis), lemon balm (melissa oficinallis), st. john’s wort (hypericum perforatum), pink savory (Thymbra satureja), dittany (origanum dictamnus), and by-products such as pomace from olives, olive leaves (olea europaea tree), orange peel (citrus sinensis), lemon peel (citrus limon), pomegranate peel (punica granatum) and mandarin peel (citrus reticulate). The fortification of the refined olive oils was performed with the use of different methodologies such as Conventional maceration (CM), Incubation shaking maceration (ISM), and Ultrasound assisted maceration (UAM). Their phenolic content and antioxidant capacity were measured with Folin–Ciocalteu assay and Ferric Reducing Antioxidant Power (FRAP) assay respectively. All methods demonstrated that different parameters such as time of maceration, temperature and sample concentration, play an important role in the fortification process of the refined olive oils. The predicyed bioavailability of the antioxidant and phenolic compounds in the fortified oils was determined with in vitro digestion and ranged from 4.84% to 53.11%. Furthermore, the refined olive oils fortified with pomace, basil, st. john's wort, and pomegranate peel presented the highest antioxidant and phenolic predicted bioavailability indices during the in vitro process compared to the control refined olive oil. Finally, fortification with natural herbs or by-products can be considered an innovative method for the improvement of the nutritional value of refined olive oils.

We review the literature on medical discourse and attempt to build a computational model of it. Medical discourse sheds a light on communication structure of patient-doctor and other communication scenarios in healthcare and should be leveraged to facilitate and automate this communication when it is possible and practical. We propose a unified framework to represent communication discourse at the meta-level, where the subject of the communication is expressed in a language object. So far, the broad range of work on medical discourse is detached from computational discourse analysis, and we explore the possibilities of filling this gap and computationally treat the peculiarities of how information is passed between the agents in a hospital setting. We select the domain of question answering (QA) against a corpus of medical documents of diverse nature to evaluate our computational model of medical discourse. It turns out that applying specific structures obtained in medical discourse studies improves the relevance and efficiency of question answering.

The Ames/quantitative structure-activity relationship (QSAR) International Challenge Projects held during 2014–2017 and 2020–2022, evaluated the performance of various predictive models. Despite the significant insights gained, the rules allowing participants to select prediction targets introduced ambiguity in model performance evaluation. This reanalysis identified the highest-performing prediction model, assuming a 100% coverage rate (COV) for all prediction target compounds and an estimated performance variation due to changes in COV. All models from both projects were evaluated using balance accuracy (BA), Matthews correlation coefficient (MCC), F1 Score (F1), and the first principal component (PC1). After normalizing the COV, a correlation analysis with these indicators was conducted, and the evaluation index for all prediction models in terms of the COV was estimated. In total, 109 models, the highest estimated BA (76.9) at 100% COV was MMI-VOTE1, reported by Meiji Pharmaceutical University (MPU). The best models for MCC, F1, and PC1 were all MMI-STK1, also reported by MPU. All models reported by MPU ranked in the top four. MMI-STK1 was estimated to have F1 scores of 59.2, 61.5, and 63.1 at COV levels of 90%, 60%, and 30%, respectively. These findings highlight the current state and potential of the Ames prediction technology.

Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.

Rural areas, as a system, face multiple challenges. Among these are population decline and attendant economic and social maladies namely demographic issues considering a scarce population. Pull factors for immigrants to go to other countries are known, nevertheless, to comprehend factors for remaining in rural areas after arriving could support a strategic local policy, and for an informed practice. The purpose of the study is to explore motivations shaping immigrants’ intentions to stay in the Alentejo, a depopulated region in Portugal, using a qualitative approach. Research questions are: What motivates immigrants to remain living in depopulated regions in Portugal? Furthermore, what contributions can practitioners and immigrants give for local policy and practice? Eight practitioners and fifteen non-European Union immigrants living in this region were interviewed between 2020 and 2021. Empirical data were analysed, supported by MaxQDA software. Results point out that the intention to remain in rural areas arise from a progressive construction, it is a process that immigrants experience to become motivated to stay long-term. Factors influencing the process include four components: 1. instrumental and material motivations; 2. emotional and social motivations; 3. motivations based on quality of life; and 4. motivations based on political dimensions. Components are conditioned by the availability of : stable and suitable jobs, access to decent and affordable housing, as well as quality of education and health services for their children; additionally to socio-emotional satisfaction, as family reunification, migrants network, integration and real intercultural living in the host community, close relationships to practitioners from social services; and quality of life, such as lower rents, peaceful and secure living conditions, granted a better future for their children as in any another place in Europe, associated finally to the simplified policy enabling one to become a legal citizen. Conclusions highlight implications for policy and practice, suggesting more investment for rural regions to reverse depopulation reality.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

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

Encouraged by the administration the gentrification process has been useful in economic terms for the reactivation of socio-cultural fabrics of historic urban spaces in decline. What was initially considered an advantage has led to the touristification of historic centres, and in turn to the alter-ation of their original use. In these settings, the demographic void caused by increasingly shunning local identity has combined with pressure from excessive tourism and the obsolescence of heritage protection bodies in charge of conservation. Given the crisis affecting the definitions of the current system, this study aims to review the envi-ronmental agents of heritage value in relation to the processes of touristification and gentrification. Data obtained from different methodologies are analysed using a multidisciplinary database, a model which enables the analysis of the relevant information from the different interacting fields. The case study focuses on the historic town centre of Seville specifically between 2015 and 2020. Elements are defined as indicators for these processes and the analysis of the case study will com-prise the main results of this research.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).

This paper deals with bistatic subsurface probing of a horizontally layered dielectric half-space by means of ultra-wideband electromagnetic pulses. A receiver collects reflections from the air-ground interface and from the gradients of dielectric permittivity in the half-space. This scenario is of interest for ground penetrating radar (GPR) applications. For the analytical description of the received signal, we developed and implemented a novel time-domain version of the coupled-wave Wentzel–Kramers–Brillouin approximation. Our solution is in very good agreement with finite-difference time-domain results, radically accelerates calculations, and effectively accounts for the protracted return signals observed in the lower part of the GPR spectrum. The paper includes results showing the application of the proposed technique to two case studies: in particular, the method was employed for the post-processing of experimental radargrams collected on Lake Chebarkul, in Russia, and to simulate GPR probing of the Moon surface, to detect smooth gradients of the dielectric permittivity in lunar regolith.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

Background: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. Methods: 3100 VABBs were retrospectively reviewed among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients’ features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate analysis. Finally, we developed a predictive multivariable model based on the features which were significantly associated with the univariate analysis outcome. Results: the upgrade rate to invasive carcinoma was 10.8 %. At univariate analysis, the risk of upgrade was significantly lower in the absence of post- biopsy residual lesion (p<0.001), age > 50 (p=0.029), and in presence of low-grade DCIS only in specimens with microcalcifications (p=0.002). According to the final multivariable model, the predicted probability of diagnostic underestimation for a patient with all the three favourable features selected at univariate analysis was 1% (95% CI: 0.3%-4%). Conclusions: An easy to use predictive model of radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.

Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)‐dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to Class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action potential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax) and conduction velocity (CV), and decreased AP duration (APD) and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that quinidine and disopyramide may be more effective against Pitx2-induced AF than propafenone by prolonging WL.

The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0-2 years of age, this study addressed 4 main objectives: 1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort, 2) Compare Candida susceptibility between isolates from the mothers and children; 3) Assess longitudinal changes in the susceptibility of the isolates collected between 0-2 years; and 4) Detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp (n=126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children’s C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable to antifungal medications from 0-2 years. For caspofungin, 29% of the children’s isolates showed an increase in MIC values from 0-2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control.

Learning systems have been very focused on creating models that are capable of obtaining the best results in error metrics. Recently, the focus has shifted to improvement in order to interpret and explain their results. The need for interpretation is greater when these models are used to support decision making. In some areas this becomes an indispensable requirement, such as in medicine. This paper focuses on the prediction of cardiovascular disease by analyzing the well-known Statlog (Heart) Data Set from the UCI’s Automated Learning Repository. This study will analyze the cost of making predictions easier to interpret by reducing the number of features that explain the classification of health status versus the cost in accuracy. It will be analyzed on a large set of classification techniques and performance metrics. Demonstrating that it is possible to make explainable and reliable models that have a good commitment to predictive performance.

The silanol activity and trace metal detection methods for chemically bonded silica gels were evaluated in silico. Test compounds with large molecular sizes may demonstrate negative results because of the possibility of indirect hydrogen bonding via short alkyl groups or siloxane of the silica gels. This hypothesis was based on the observation of weak hydrogen bonding energy values similar to those observed in the study of the alkyl group effect on the hydrogen bonding of alkanols. Consequently, smaller molecules may be a better choice for the analysis of bonded-phase quality.

The Dubai Digital Government launched its recent guidelines, which call for artificial intelligence systems to be subject to legal accountability. This study discusses the extent to which autonomous robots can be granted legal personality in UAE law and the consistency of this approach with the provisions of Islamic jurisprudence. This research paper answered two main questions: First, the extent to which these guidelines are considered the beginning of work on granting legal personality to AI systems in the UAE. Second, what form of legal personality can be given to autonomous robots in UAE law to be consistent with the provisions of Islamic jurisprudence as a primary source of legislation in the country? The research concluded the impossibility of considering autonomous robots as a "thing" and classifying them within the concept of "persons." It also concluded that it is possible to give them legal personality according to two legislative solutions: granting them partial or incomplete performance eligibility like minors.

A large number of smart devices (things) are being deployed with the swift development of Inter- net of Things (IOT). These devices, owned by different organizations, have a wide variety of services to offer over the web. During a natural disaster or emergency (i.e., a situation), for example, relevant IOT services can be found and put to use. However, appropriate service matching methods are required to find the relevant services. Organizations that manage situation responses and organizations that provide IOT services are likely to be independent of each other, and therefore it is difficult for them to adopt a common ontological model to facilitate the service matching. Moreover, there exists a large conceptual gap between the domain of discourse for situations and the domain of discourse for services, which cannot be adequately bridged by existing techniques. In this paper, we address these issues and propose a new method, WikiServe, to identify IOT services that are functionally relevant to a given situation. Using concepts (terms) from situation and service descriptions, WikiServe employs Wikipedia as a knowledge source to bridge the conceptual gap between situation and service descriptions and match functionally relevant IOT services for a situation. It uses situation terms to retrieve situation related articles from Wikipedia. Then it creates a ranked list of services for the situation using the weighted occurrences of service terms in weighted situation articles. WikiServe performs better than a commonly used baseline method in terms of Precision, Recall and F measure for service matching.

In this letter we investigate if SARS-CoV-2 RNA is involved in the increased ageing of alveolar cells. Our in silico study is explorative. With the results we are able to outline experiments with AEC2 repair of bleomycin damaged alveolar cells. If AEC2 repair capability is diminished by spike RNA then perhaps this result provides a first step on a route to treat immortal lung cancer cells.

Warren Weaver, writing about the function that science should have in mankind’s developing future, ideas and ideals, proposed to classify scientific problems into ‘problems of simplicity’, ‘problems of disorganised complexity’, and ‘problems of organised complexity’ — the huge complementary class to which all biological, human, and social problems belong. Problems of simplicity have few components and variables and have been extensively addressed in the last 400 years. Problems of disorganised complexity have a huge number of individually erratic components and variables, but possess collective regularities that can be analysed by resourcing to stochastic methods. Yet, problems of organised complexity do not yield easily to classical or statistical treatment since interrelations among phenomenon elements change during its evolution alongside commonly used state variables, affecting behaviour and outcome. Moreover, organisation, the focal point in this complementary class, is still an elusive concept despite the gigantic efforts undertaken since a century ago to tame it. This paper addresses the description, representation and study of phenomena in the ‘problems of organised complexity’ class. Grounded on relational mathematical constructs, a theoretical framework providing operational definitions and schemes for formally modelling organisations and interaction of organisations is introduced. This framework extends the general systems’ concept and provides a novel perspective for addressing organised complexity phenomena as a collection of interacting organisations.

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

The social vulnerability approach (SV) has set up that social inequalities and disadvantages have gone beyond monetary poverty in the last years, since the process is built at different scales. In its objectives, the SV multidimensional measurement is contemplated as a priority tool to monitor the compliance of the first goal – eliminate poverty in all its forms. Therefore, the objective of this research is to calculate the SV of the fishing communities of the Gulf of Ulloa (GU), Mexico by macro-markers to subsequently contrast them with field micro-data, and finally perform a behavior scenario, considering the current public policies restrictive to fishing in such areas. The results showed significant differences depending on the type of information used, obtaining a contingency coefficient of 83.42%, which indicates that the calculus depends strongly on the data used and suggesting that macro-data may be masking the true SV values in the area, in such a way they could be severely underestimated. Even though the context at micro-scale is not the only one, SV should be calculated to analyze the fishing communities since coastal fishery represents almost the total livelihood of the inhabitants. Nevertheless, these communities confront numerous local and global threats, and these pressures on SV put their livelihoods, well-being, food security and traditional lifestyle at risk. Therefore, the role of researching human dimensions and governance is not only basic but also urgent to turn to sustainable socioeconomic management.

This review focuses on developments that quantify grain quality with a range of spectral sensors in an on-farm setting. If the application of sensor technologies were expanded and adopted on-farm, growers could identify the impact and manage the harvesting operation to meet a range of quality targets and provide an economic advantage to the farming enterprise.

Globally, between 10% and 15% of couples experience infertility. Given the high demand for Assisted Reproductive Techniques (ART), there is growing interest in exploring modifiable factors influencing their outcomes. In this context, the objective of this review was to investigate the impact of adherence to the Mediterranean Diet (MD), recognized for its benefits in reproductive health, on ART outcomes. Methodology: A systematic review was conducted following the PRISMA methodology. International databases were consulted, selecting studies published between 2010 and 2023, in English and Spanish, involving patients aged 18-55, and examining intermediate and/or clinical outcomes of ART. Systematic reviews, meta-analyses, and animal studies were excluded. Results: Of the 9 included articles, 5 found statistically significant associations between adherence to the MD and positive outcomes in ART, such as a higher number and quality of embryos, clinical and biochemical pregnancy, and live births. However, other studies found no such associations. Conclusions: There is a potential association between adherence to the MD and ART outcomes. The evidence is very limited, necessitating further investigation.

This study explores the integration of Artificial Intelligence (AI) and collaborative robotics in industrial surface finishing, focusing on feature detection on object reflective surfaces using neural networks in computationally constrained environments. Central to this investigation is the utilization of cameras considered as sensors that can capture detailed images of reflective surfaces. These images are then analyzed by a custom neural network, demonstrating the feasibility of feature detection with non-powerful computers. The public dataset for recognizing light reflection defects, available in the SPADD repository, supports this approach. Employing open-source tools like Darknet YOLOv3 and Yolo\_mark, this method proves particularly advantageous for small and medium-sized enterprises (SMEs) due to its low cost and maintenance requirements. This research highlights the challenges of AI and collaborative robotics in industrial applications, especially in adapting to varying conditions and the need for continuous training with new data coming from several sensors. Looking ahead, plans are in place to integrate this system with cobot-assisted polishing tasks, using cameras to enhance manufacturing efficiency and quality. This work contributes to the broader understanding of practical applications of AI in industrial automation, surface finishing processes, and the effective use of sensor technology.

Current article presents the study of psychological wellbeing of adolescents (n=168, age 15-17) gifted in math, humanities and sports and educated in advanced programs for gifted children. Theoretical framework of this study is eudemonic concept of psychological wellbeing by C. Ryff. Psychological wellbeing is measured with Ryff wellbeing scales in Russian adaptation by L.V. Zhukovskaya and E.G. Troshikhina. The study is aimed at understanding differences in psychological wellbeing of gifted teenagers connected to gender and type of giftedness. The results suggest that general wellbeing score did not differ for adolescents with different types of giftedness or of different genders. Separate components of psychological wellbeing, such as purpose in life and self-acceptance, are influenced by activity connected to the talent. Gender differences are subjected to age-specific trends of personal development in adolescence. Type of giftedness might reinforce these trends.

Abstract: The use of IVF and related procedures has offered opportunities for couples to conceive who otherwise would remain childless. This technology is often viewed as the only option but is very expensive and not highly effective. ln an effort to improve access to care, governments are attempting to provide funding. In Ireland for example the Health Service Executive (HSE) has recently made IVF funding available through Regional Fertility Hubs. for couples who qualify. However, this policy has threatened a less invasive approach available in Ireland that can help many couples before IVF is employed. We propose that a newly emerging “medical treatment process” called Restorative Reproductive Medicine (RRM), combined with methods or apps that track biomarkers of the menstrual cycle as a prerequisite option for appropriate patients. To illustrate the effectiveness, we compared live birth rates from an established Irish RRM clinic that uses the ChartNeo app to HFEA (Human Fertilization and Embryology Authority) data, both from 2019. RRM treatment had a live birth rate of 40.4% compared to 24.4% per treatment cycle for IVF (P>0.0001). RRM twin pregnancy rate was 2.5% compared to 7% for IVF. RRM babies were usually full term and normal birth weight. Therefore, RRM is less expensive, less invasive, and more effective than IVF for most patients. This merits further evaluation and support by the HSE and other global authorities guiding health policy.

Although all isolates of the foodborne pathogen Listeria monocytogenes are considered to be pathogenic, epidemiological evidence indicates that certain serovar 4b lineages are more likely to cause severe invasive (neuromeningeal, maternal-fetal) listeriosis. Recently described as L. monocytogenes “hypervirulent” clones, no distinctive bacterial trait has been identified so far that could account for the differential pathogenicity of these strains. Here we discuss some preliminary observations in experimentally infected mice suggesting that serovar 4b hypervirulent strains may have a hitherto unrecognized capacity for prolonged in vivo survival. We propose the hypothesis that protracted survivability in primary infection foci in liver and spleen –first target organs after intestinal translocation– may cause L. monocytogenes serovar 4b hypervirulent clones to have a higher probability of secondary dissemination to brain and placenta.

With Internet of Things (IoT) gaining presence throughout different industries a lot of new technologies have been introduced to support this undertaking. Implications on one such technology, wireless systems allowed for the use of different communication methods to achieve the goal of transferring data reliably, with more cost efficiency and over longer distances. Anywhere from a single house with only a few IoT devices such as a smart light bulb or a smart thermostat connected to the network, all the way to a complex system that can control power grids throughout countries, IoT has been becoming a necessity in everyday lives. This paper presents an overview of the devices, systems and wireless technologies used in different IoT architectures (Healthcare, Vehicular Networks, Mining, Learning, Energy, Smart Cities, Behaviors and Decision Making), their upbringings and challenges to this date and some foreseen in the future.

Background: Redo mitral valve surgery is the standard of care for failed mitral bioprostheses or recurrence of mitral regurgitation after repair. Nonetheless, catheterbased valve-in-valve (ViV) or valve-in-ring (ViR)-procedures increasingly become viable alternatives in high risk subpopula-tions. Despite reported good initial results, only little is known about longer-term outcomes. The present series report long-term outcomes of transcatheter mitral ViV- and ViR-procedures. Methods: All consecutive patients (n=54) undergoing transcatheter mitral ViV- or ViR-procedures for failed bioprostheses or recurring regurgitation after mitral repair were retrospectively en-rolled in the time period between 2011 and 2021. The mean age was 76.5 ± 6.5 years, and 30 (55.6%) of the patients were male. The procedures were done using a commercially available balloon-expandable transcatheter heart valve. Clinical and echocardiographic follow-up data were obtained out of the hospital’s database and analyzed. Follow-up reached up to 9.9 years with a total of 164.3 patient-years. Results: A total 25 patients received a ViV- and 29 patients a ViR-procedure. Both groups were at high surgical risk with an STS-PROM of 5.9 ± 3.7 % in ViV- and 8.7 ± 9.0% in ViR-patients, respectively (p<0.01). The procedures itself were mainly unevent-ful with no intraoperative deaths and a low conversion rate (n=2/54; 3.7%). VARC-2 procedural success was low (ViV 20.0% and ViR 10.3%; p=0.45), which was either driven by high rates of transvalvular pressure gradients “>5mmHg” (ViV 92.0% and ViR 27.6%; p<0.01) or residual regurgitation “>trace” (ViV 28.0% and ViR 82.7%; p<0.01). ICU-stay was prolonged in both groups (ViV 3.8 ± 6.8 days and ViR 4.3 ± 6.3 days; p=0.96) with acceptable hospital stay (ViV 9.9 ± 5.9 days and ViR 13.5 ± 8.0 days; p=0.13). Despite 30-days mortality was acceptable (ViV 4.0% and ViR 6.9%; p=1.00), the mean posthospital survival time was disappointingly low (ViV 3.9 ± 2.6 years and ViR 2.3 ± 2.7 years; p<0.01). Overall survival I the entire group was 33.3%.Cardiac reasons for death were frequent in both groups (ViV 38.5% and ViR 52.2%). Cox-regression analysis identified ViR-procedures as a predictor of mortality (HR 2.36, CI 1.19 - 4.67, p=0.01). Conclusions: Despite acceptable immediate outcomes in this high-risk subpopulation, long-terms results are discouraging. Transvalvular pressure gradients as well as residual regurgitations remained drawbacks in this real-world population. The indication for catheterbased mitral ViV- or ViR-procedures thoughtfully must be made in consideration of conventional redo-surgery or conservative treatment.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

Extensive in-situ resource utilisation (ISRU) will be essential to enable long-duration stays on Luna and Mars and reduce reliance on resupply from Earth. Early development of ISRU technologies has focused on standalone capabilities for specific targets related to life support and ascent propellant. An unexplored opportunity remains for greatly expanding the scope of materials that can be supplied by ISRU, and for integrating various technology platforms into a larger system. Recent advances in power-to-X technology aimed at decarbonising the global economy have made it possible to drive key chemical processes using electricity with small-scale, modular reactor. This paper proposes a vision for an integrated system of ISRU processes based on power-to-X technology to produce oxygen, hydrogen, water, methane, polymers, metal alloys, and synthetic fertilisers, using Martian regolith, atmosphere, and ice. A ‘building block’ strategy is adopted to convert raw materials into versatile intermediaries, which can then be combined to form essential products. A wider range of raw materials are available on Mars compared to Luna, suggesting greater opportunity for ISRU deployment to compensate for the greater time and cost requirements for a Mars resupply mission.

The article presents the methodology for classifying economic regions with regards to selected factors that characterize a region, such as: the economic structure of the region, and thus the share of individual sectors in the economy; employment; the dynamics of the development of individual sectors expressed as an increase or decrease in production value; the population density in the region and also the level of occupational safety. Cluster analysis, which is a method of multidimensional statistical analysis available in Statistica software, was used to solve the task. The proposed methodology was used to group Polish voivodships with regards to the speed of economic development and occupational safety in the construction industry. Data published by the Central Statistical Office was used for this purpose, such as the value of construction and assembly production, the number of people employed in the construction industry, the population of an individual region and the number of people injured in occupational accidents.

Analytical instruments used for scientific research and education are often expensive. This limitation poses a challenge for schools and educators in low-income countries to provide practical science training to students. To address this problem, the improvisation of analytical instruments and instructional materials has emerged as a viable solution. By incorporating practical experiments into science education, students have the opportunity to engage directly with scientific instruments, conduct investigations, and collect data. This hands-on approach fosters a deeper understanding of scientific principles, enhances critical thinking skills, and cultivates scientific mindsets among students. Herein, we review and discuss, step-by-step, the approach of using a smartphone for quantitative analysis, referred to as smartphone digital image colorimetry (SDIC). SDIC, with its practicality and accessibility, utilizes smartphone digital cameras for image acquisition and the freely available image processing programs, such as ImageJ and smartphone Apps, for image quantification. Using SDIC can enable students in low-income countries to develop essential scientific skills, including critical thinking, data interpretation, and an evidence-based approach to scientific research. By leveraging the ubiquity and affordability of smartphone technology, SDIC offers an accessible and cost-effective approach to practical science education, bridging the gap between theory and practice in resource-constrained settings.

In this paper, we discuss major issues of mathematics teaching and learning in Nepal. The issues coming from theories such as social and radical constructivism suggest that teachers are not trained to use such approach in teaching mathematics, and there is a lack of teaching aids and materials and technological tools. The issues related to social aspects are gender issues, language issues, social justice issues, and issues related to the achievement gap. The cultural issues are related to the diversity of language and ethnicity. The issues related to political aspects are equity and access, economic status, pedagogical choice, and professional organizations and unions. The issues related to technology include the technological skills, use of technology, and affordance. Finally, we suggest that all the stakeholders should pay attention to resolving these issues by improving the curriculum, training teachers, resourcing the classroom with locally made and new technological tools.

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

China is out of extreme poverty in 2020 on schedule and one decade in advance to fulfill the UN 2030 Agenda for Sustainable Development Goals (SDGs), and became the first developing country to alleviate poverty in half century. Therefore, a large numbers of effective approaches are emerging, and the intellectual’s technology-led poverty reduction, which locally known as the “Straw Hat University”initiated by “Farmer's professor”mode, is the most tried and tested approach motivated by the intellectual’s “Serve the people” tradition and supported by the all nation. This research conduct case analysis with three most remarkable organic intellectuals as Agronomist Yuan longping, Mycologist Lin Zhanxi and Plant pathologist Zhu Youyong with their bridging gaps in food security, regional imbalance and ethnic disparity respectively to sort out the sustainable modules and universal experiences. The conclusion indicates that“Farmer's Professor” Initiated “Straw Hat University” is an effective approach to solve human beings’ development problems and benefit the livelihoods, especially in the under development regions; and the authentic down to earth experiments into productivity as well as the Intellectual property transformation is the perfect path to deploy offline and online resources building the effective production and supply chain to integrate industries by intellectual’s critical innovation.

Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.

The bio-oil was largely produced by thermal pyrolysis of Jatropha-derived biomass wastes (denoted as Jatropha bio-oil) using a Pilot Plant with a capacity of 20 kg h-1 at Thailand Institute of Scientific and Technological Research (TISTR), Thailand. Jatropha bio-oil is an unconventional type of bio-oil, which is mostly composed of fatty acids, fatty acid methyl esters, fatty acid amides and derivatives, and consequently it contained large amounts of heteroatoms (oxygen ~ 20 wt.%, nitrogen ~ 5 wt.%, sulfur ~ 1000 ppm.). The heteroatoms, nitrogen especially, are highly poisonous to the metal or sulfide catalysts for upgrading of Jatropha bio-oil. To overcome this technical problem, we reported a stepwise strategy for hydrotreating of 100 wt% Jatropha bio-oil over mesoporous sulfide catalysts of CoMo/γ-Al2O3 and NiMo/γ-Al2O3 to produce drop-in transport fuels, such as gasoline- and diesel-like fuels. This study is very different from our recent work on co-processing of Jatropha bio-oil (ca. 10 wt%) with petroleum distillates to produce a hydrotreated oil as a diesel-like fuel (Chen et al., Catalysts 2018, 8, 59; http://dx.doi.org/10.3390/catal8020059). Jatropha bio-oil was pre-treated through a slurry-type high pressure reactor under severe condition, resulting in a pre-treated Jatropha bio-oil with relatively low amounts of heteroatoms (oxygen < 20 wt.%, nitrogen < 2 wt.%, sulfur < 500 ppm.). The light and middle distillates of pre-hydrotreated Jatropha bio oil was then separated by distillation at temperature below 240 oC, and the temperature of 240-360 oC. Deep hydrotreating of light distillates over sulfide CoMo/γ-Al2O3 catalyst was performed on a batch-type high pressure reactor at 350 oC and 7 MPa of H2 gas for 5 h. The hydrotreated oil was a gasoline-like fuel, which contained 29.5 vol.% of n-paraffins, 14.4 vol.% of iso-paraffins, 4.5 vol.% of olefins, 21.4 vol. % of naphthene compounds and 29.6 wt.% of aromatic compounds, and little amounts of heteroatoms (nearly no oxygen and sulfur, and less than 50 ppm of nitrogen), corresponding to an octane number of 44, and it would be suitable for blending with petro-gasoline. The hydrotreating of middle distillates over sulfide NiMo/γ-Al2O3 catalyst using the same reaction condition produced a hydrotreating oil with diesel-like composition, low amounts of heteroatoms (no oxygen and less than 50 ppm of sulfur and nitrogen), and a cetane number of 60, which would be suitable for use in drop-in diesel fuel.

The analysis presented is based on actual GHU energy demand. The special feature of this load is the existence of strong daily fluctuations in energy consumption, especially during the summer months. This study presents a methodology for managing such loads with the main objective of maximizing the operating efficiency of MG.

Lean is one of the systematic approach to achieve higher value for organizations through eliminate non-value-added activities. It is an integrated set of tools, techniques, and principles designed to optimize cost, quality and delivery while improving safety. In Vietnam, industry waste management and treatment has become serious issue. The aim of this research is to present the effective of Lean application for industrial wastes collecting and delivery improvement. Through a case study, this paper showed the way of Lean tools and principles applied for wastes management and treatment such as Value Stream Mapping, Pull system, Visual Control, and Andon.... to get benefit on both economic and environment. In addition, the results introduced a good experience for Vietnamese enterprises in cost saving and sustainable development in waste management.

Ensuring access to water, sanitation, and hygiene (WASH) facilities, coupled with behavior change education in schools, is fundamental for fostering a conducive learning environment and promoting principles of inclusion, dignity, and equality. This study focuses on 12 primary schools in Anápolis, Brazil, encompassing 4,394 students and 248 teachers. WASH assessments were conducted through a questionnaire, observation of water and sanitation facilities and structures, and microbiological analysis. Over the period 2018 to 2020, the proportion of schools with safely managed drinking water surged from 42% to 92%. However, sanitation conditions in the schools were categorized as a basic level, with hygiene services rated as limited in 92% of the schools due to the absence of soap. While this study reveals that Anápolis schools generally align with WASH guidelines for basic/advanced drinking water services, there is a crucial need for enhancements in both hardware and software facilities to address sanitation and hygiene challenges.

This study reports fractal analysis of one-year radon in groundwater disturbances from five stations in China amid the catastrophic Wenchuan (Mw=7.9) earthquake of May 12, 2008 (day 133). Five techniques are used (DFA, fractal dimensions with Higuchi, Katz, Sevcik methods, power-law analysis) in segmented portions glided throughout each signal. Noteworthy fractal areas are outlined in the KDS, GS, MSS station data, while the portions were non-significant for PZHS and SPS. Up to day 133 critical epoch DFA-exponents have 1.5<=a<2.0 with several above 1.8. Fractal dimensions exhibit Katz’s D around 1.0-1.2, Higuchi’s D between 1.5-2.0 and Sevcik’s D between 1.0-1.5. Several power-law exponents are above 1.7 and numerous above 2.0. All fractal results of KDS-GS-MSS stations are further analysed using a novel computerised methodology which locates the exact out-of-threshold fractal areas and combines the outcomes of different methods per five, four, three, and two (maximum 13 combinations) versus nineteen Mw<=5.5 earthquakes of the area. Most different-technique coincidences are before the great Wenchuan earthquake and its post-earthquakes. This is not only with one method, but with 13 different methods. Other interpretations are also discussed.

The ongoing electrification of the heat and transport sectors is expected to lead to a substantial increase in peak electricity demand over the coming decades, which may drive significant investment in network reinforcement in order to maintain a secure supply of electricity to consumers. The traditional way of security provision has been based on conventional investments such as the upgrade of the capacity of electricity transmission or distribution lines. However, the energy storage technology can also provide security of supply, thereby constituting a cost-efficient alternative to expensive conventional reinforcements. In this context, the current paper presents a methodology for the economic quantification of the security contribution of energy storage. This methodology makes use of mathematical optimization for the calculation of the F-factor metric, which reflects the optimal amount of peak demand reduction as compared to the power capability of the energy storage asset. In this context, a case study is presented in which the security contribution of energy storage is analyzed as a function of its power capability, energy capacity and efficiency as well as of characteristics of load patterns.

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

Amongst the advantages of using Worldwide Interoperability Microwave Access (WiMAX) technology at the last-mile level as access technology include an extensive range of 50 km Line of Sight (LOS), 5 to 15 km Non-Line of Sight and few infrastructure installations compared to other wireless broadband access technologies. Despite positive investments in ICT fibre infrastructure by developing countries, including Botswana, servicing end-users is subjected to high prices and service disparities. The alternative, the Wi-Fi hotspot initiative by the Botswana government, falls short as a solution for last-mile connectivity and access. This study used OPNET simulation Modeller 14,5 to investigate whether Botswana’s national broadband project could adopt WiMAX IEEE 802.16e as an access technology. Therefore, using the simulation method, this paper evaluates the WiMAX IEEE 802.16e/m over three subscriber locations in Botswana. The results obtained indicate that the deployment of the WiMAX IEEE 802.16e standard can solve most of the deployment issues and access at the last-mile level. Although the findings suggest that WiMAX IEEE 802.16e is more suitable for high-density areas, it could also solve rural areas’ infrastructure development challenges and provide the required high-speed connectivity access. However, unlike the Wi-Fi initiative, which requires more infrastructure deployment and less on institutional and regulatory frameworks, the deployment of WiMAX IEEE802.16e requires institutional and regulatory standards.

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

Background and purpose: Chronic kidney disease (CKD) is a common chronic disease usually associated with cardiovascular disease (CVD), and premature death and millions of people are at increased risk for CKD. As this disease is extremely complex, multidisciplinary care (MDC) is needed to provide complete and continuous care. Usually, the nephrology units need coopera-tion from several other Healthcare Professionals (HCPs) such as cardiologists, nutritionists, ob-stetricians, and so forth. All modalities of treatments, peritoneal dialysis (PD) and Hemodialysis (HD) require HCPs and patients to develop a variety of skills to effectively deliver and manage dialysis tasks in the center or at home. Information and Communication Technology (ICT) in-terventions can offer tools that provide HCPs and patients with tools that facilitate the manage-ment of kidney patients in centers or at home. ICT interventions can allow to automate registra-tions, videoconferencing, minimize the geographic burden and resource cost savings. ICT can be the best way to promote cost saving on health spending and ensure the sustainability of the health system and, the environment as well. In the Iberian Peninsula, kidney patients consume about 3% of the total cost of healthcare. The cost of kidney transplants and dialysis is around 1.8 billion euros annually, and 75 % of this amount goes to dialysis treatment. Objective: This study aimed to evaluate and analyze the opinion of Healthcare Professionals (HCP) in Nephrology units about the Intervention of ICT in nephrology care and the Clinical benefits results from the use of ICT in Nephrology Services and dialysis Units in Portugal and Spain. Thus we collected the opinion of Health care professionals concerning the role of ICT intervention in nephrology. Understanding HCPs' feelings and attitudes is essential to understand if such technologies are correctly adjusted to the workflow and really bring huge benefits for the clinical practice of nephrology and also what features need improvement and what should be implemented in the future. ICT intervention has been implemented to promote better healthcare in nephrology units and improve patient outcomes. In the Survey, we intended to evaluate nephrology HCPs' opinions concerning the ICT interventions, in nephrology, represented by several tools that al-low the HCPs to implement solutions such as Remote Patient Monitoring(RPM); Remote Moni-toring of Treatment (RMT); Tele homecare; Telehealth (Tele-nephrology); Home Dialysis; mHealth; mobile App; Web Portal, Telemedicine, and so forth. Key Points: In many countries particularly in the Iberian Peninsula (Portugal and Spain) the incidence of CKD is substantially high. The “treatments” for kidney disease have not improved substantially over the past 50 years, leaving too many kidney patients with a poor quality of life and reduced life expectancy. This situation is associated with staggering aggregate annual costs amounting to €140 billion per year in Europe, more than the annual healthcare costs of cancer or diabetes [1]. The increased daily use of information and communication technologies may lead to the need for healthcare professionals to incorporate technology use competencies into practice.

Oxidative stress negatively affects folliculogenesis and embryo development. However, a reliable and biologically accurate indicator of oxidative stress does not yet exist. On these bases, the aim of this study was to assess -and compare- blood and follicular fluid (FF) redox status in 45 infertile subjects (and 45 age-matched controls) undergoing in vitro fertilization (IVF) and to establish its connection with the outcome of IVF. Blood and FF were obtained at the time of egg retrieval and immediately analyzed. Firstly, ROS production in blood leukocytes and in granulosa cells was assessed. Oxidative stress markers in blood and in granulosa cells resulted significantly (p<0.001) increased in infertile patients compared to controls. Then, a redox index was obtained in plasma and in FF of patients and controls. The main findings emerging from our study in infertile women are: i) blood oxidative stress reflects FF oxidative stress as demonstrated by the significant correlation between blood redox markers and FF redox markers; ii) a significant correlation between oxidative stress parameters and the considered IVF outcomes is present. We suggest the strict monitoring of the redox parameters for the improvement of assisted reproductive techniques success rate and infertility management.

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

Leptospirosis remains an important worldwide zoonotic disease caused by Leptospira spp affecting human and animals. This research aims to study the virulent-associated secreted proteins (protein secretome) of pathogenic Leptospira interrogans serovar Icterohemorrhagiae strain RGA (Leptospira RGA) transition from the environment to mammalian physiological osmolarity, temperature (37 °C) and carbon dioxide concentration (5% CO2) conditions for 24 h. Mass Spectrometry and bioinformatics approaches, we identified 69 potential secreted proteins from the culture supernatant of the Leptospira RGA isolate. We discovered transporters and porins such as phosphate porin, outer membrane efflux, ompA family protein, and polymer-forming cytoskeletal family protein under hyperosmotic condition. Under heat stress, degradation enzymes included zinc metallopeptidase, M23 family (LA3456, LA0709), Rhs family protein (LA1765), thermolysin metallopeptidase; / hydrolase family (LA1345, LA2501). Oxidative stress response proteins induced by osmolarity and temperature shifts included chaperon GrpE, DnaK (LA3705), antioxidants, i.e., thiol-specific redoxin, and peroxiredoxin (LA2809). In response to the in vivo transition, metabolic and other enzymes involved in energy production (COG:C), amino acid metabolism and transport (COG:E), and lipid metabolism and transport (COG:I), as well as moonlighting proteins functionally binding to plasminogen and fibronectin and regulating transcription, were also discovered. An overview of secreted proteins will supplement our understanding of Leptospira biology and pathogenesis during infection and also in response to environmental stimuli and their potential virulent determinants have the potential for developing leptospirosis vaccines and diagnosis.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. In-process EBM monitoring for quality assurance purposes has been a popular research area. Electronic imaging has recently been investigated as one of the in-process EBM data collection methods, alongside thermal/ optical imaging techniques. Despite certain capabilities of an electronic imaging system have been investigated, experiments are yet to be carried out to benchmark one of the most important features of any imaging systems – spatial resolution. This article addresses this knowledge gap by: (1) proposing an indicator for the estimation of spatial resolution which includes the Backscattered Electrons (BSE) information depth, (2) estimating the achievable spatial resolution when electronic imaging is carried out inside an Arcam A1 EBM machine, and (3) presenting an experimental method to conduct edge resolution evaluation with the EBM machine. Analyses of experimental results indicated that the spatial resolution was of the order of 0.3mm-0.4mm when electronic imaging was carried out at room temperature. It is believed that by disseminating an analysis and experimental method to estimate and quantify spatial resolution, this study has contributed to the on-going quality assessment research in the field of in-process monitoring of the EBM process.

This work studies a novel low voltage (<60 V) hybrid system that supports engine boosting and downsizing in addition to start-stop, regenerative braking, and constrained torque assist/regeneration. The hybrid power split supercharger (PSS) shares a 9 kW motor between supercharging the engine or providing hybrid functionalities through a planetary gear set, a brake and a bypass valve. The PSS operation is limited to only one of the parallel hybrid or boosting modes at a time, necessitating a highly optimized decision making algorithm to select the device mode and power split ratio. In this work an adaptive equivalent consumption minimization strategy (A-ECMS) is developed for energy management of the PSS. The A-ECMS effectiveness is compared against a dynamic programming (DP) solution with full drive cycle preview through hardware-in-the-loop experiments on an engine dynamometer testbed. The experiments show that the PSS with A-ECMS reduces a vehicle fuel consumption by 18.4% over standard FTP75 cycle compared to a baseline turbocharged engine, while global optimal DP solution decreases the fuel consumption by 22.8% compared to baseline.

Much remains to be understood for delayed ultraweak photon emission (UPE) from organism in association with oxidative burst following external perturbation, a phenomenon that has been experimented for over three decades. Delayed UPE often decays hyperbolically; yet, it is not uncommon to have delayed UPE that reveals first-order kinetic patterns characterized by single-exponential, double exponential, or multi-exponential changes. Some delayed UPEs also presented transient patterns that are characteristic of second-order responses. A soliton-based photon-storage model has addressed the hyperbolic decaying pattern of delayed UPE; however, there are questions outstanding regarding modeling other non-hyperbolic kinetics as well as the large range of temporal scales of delayed UPE that can vary from 8.5 microseconds to many hours. This work proposes an alternative, phenomenological model-framework for interpreting the various kinetic patterns of delayed UPE following stress. The delayed UPE is considered to be governed by two sequential phases: a stress-transfer phase that transforms the external stress to photo-genesis for emitting photons, and a photon-diffusion phase that transmits the photons emitted by the photo-genesis to the surface of organism for being detected as delayed UPE. Time-resolved photon diffusion analysis reveals that any delayed UPE in organism with a delay time >100ns cannot be addressed by the inherent temporal spread that realistic tissue scattering will cause. A slow stress-transfer phase is thus required to explain the delay time-scales of delayed UPE at a minimum of 8.5 µs as reported experimentally. The stress-transfer phase is hypothesized to carry the following types of responses: single or multiple 1st-order low-pass, single 2nd-order low-pass with various damping factors, and single 2nd-order band-pass with various damping factors. A single 1st–order low-pass response with a time-varying kinetic rate is also analyzed. The responses of these modeled pathways to bolus and step inputs demonstrate that a kinetic pattern other than the exact single-exponential one may have multiple causes.

The dimorphic, soil-dwelling fungus Coccidioides is the causative agent of coccidioidomycosis and is a reemerging pathogen of human health concern. Despite increasing incidence and isolations of the organism outside of its theoretical environmental range, much of Coccidioides epidemiology, including complete host range, remains unknown. Feral swine (Sus scrofa) are an invasive species distributed throughout the United States that may play a role in fungal ecology due to their behavioral associations with soil. To address this, we evaluated seven feral swine for susceptibility to Coccidioides. After intranasal inoculation with 106.2 arthroconidia of C. posadasii, no pigs displayed signs of clinical disease, nor did any exhibit antibodies by AGID testing. Histopathologic evaluation did not reveal the presence granulomatous lesions, and fungal spherules or endospores were not observed in any of the tissue sections examined, although individuals had significant comorbidities, most notably Metastrongylus nematodes in the lungs. Despite the absence of lesions and organisms histologically, C. posadasii was isolated by culture from the lung and mediastinal lymph node of two pigs, indicating active infection. These results suggest that feral swine are mildly susceptible to acute Coccidioides infection and may aid in fungal dispersal due to the presence of spherules in tissues post-mortem.

There are increasing calls in education for deeper integration of disciplines and better preparation for the personal and job challenges of a fast-changing and smarter society. Thus, we need to search for new effective didactic strategies. However, current classrooms are isolated. They practically never connect. This hinders the exchange of ideas. It inhibits imitation and recombination, the basic blocks of cultural evolution and innovation. In this paper, we analyze online inter-class tournaments. These are lessons where entire elementary or middle school classes interconnect synchronously and play an educational game. These are new types of academic activities, and only possible thanks to digital communication technology. In this paper, we examine four online tournaments, we analyze how feasible it is to carry them out and the benefits they bring. One tournament is for teaching machine learning and statistics. The second one teaches the conservation of momentum in physics and an engineering optimization challenge. The third tournament is for learning to solve word problems. The fourth one is for teaching natural and sexual selection along with developing statistical and population thinking. We found that these inter-class tournaments are feasible to implement in schools and that they are a promising mechanism to facilitate imitation, recombination, and innovation of teaching strategies.

MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of Flight) is a type of mass spectrometry (MS) that has been widely implemented for the rapid identification of microorganisms over the last decade. The accuracy and flexibility of this method has encouraged researchers to implement the analysis of protein spectra obtained by MALDI-TOF for the discrimination of close-related species and bacterial typing. In this study, a standardized methodology based on the detection of species-specific protein peaks from the spectra obtained with MALDI-TOF is described. The methodology was applied to a collection of Cryptococcus spp. (n=70) previously characterized by Amplified Fragment Length Polymorphism (AFLP) and sequencing of the ITS1-5.8S-ITS2 region. An expanded ad-hoc database was also built for their discrimination with MALDI-TOF. This approach did not allow the discrimination of the interspecies hybrids. However, the performance of peak analysis with the application of the PLS-DA and SVM algorithms in a two-step analysis allowed 96.95% and 96.55% correct discrimination of C. neoformans from the interspecies hybrids, respectively. Besides, PCA analysis prior to SVM provided 98.45% correct discrimination of the 3 analyzed species in a one-step analysis. The method is cost-efficient, rapid and user-friendly. The procedure can also be automatized for an optimized implementation in the laboratory routine.

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

Abstract This essay presents a real-world demonstration of the evidence-based science communication process, showing how it can be used to create scientific data visualizations for public audiences. Visualizing research data can be an important science communication tool. Maximizing its effectiveness has the potential to benefit millions of viewers. As with many forms of science communication, creators of such data visualizations typically rely on their own judgments and the views of the scientists providing the data to inform their science communication decision-making. But that leaves out a critical stakeholder in the communications pipeline: the intended audience. Here, we show the practical steps that our team - the Advanced Visualization Lab at the University of Illinois at Urbana-Champaign - has taken to shift towards more evidence-based practice to enhance our science communication impact. We do this using concrete examples from our work on two scientific documentary films, one on the theme of ‘solar superstorms’ and the other focusing on the black hole at the center of the Milky Way galaxy. We used audience research with each of these films to inform our strategies and designs. We describe how such research evidence informed our understanding of ‘what works and why’ with cinematic-style data visualizations for the public. We close the essay with our key ‘take home’ messages from this evidence-based science communication process.

Water reuse for irrigation is increasingly recognized as an essential and economical strategy in areas with water scarcity. A simple, low-cost, low-maintenance, and highly efficient Pond-In-Pond (PIP) treatment system can be used for wastewater reuse. PIP is a treatment technology in which two types of ponds -- anaerobic and aerobic -- are combined into a single pond and consist of a deeper inner section entirely submerged within the outer pond. Previous studies on PIPs and PIP-like systems have reinforced the potential for reuse through promising performance results with BOD removal over 80% and a reduction in land area requirements by approximately 40%. Yet, no prior efforts have been made to understand the performance mechanism of such systems. This study makes use of two, 2-D modeling tools in developing a fundamental understanding of PIP flow dynamics and the expected performance. The modeling results showed that the PIP configuration offers improved flow diversion along with reduced flow velocity. Additionally, the PIP retained approximately 17% more (p<0.05) particles than the traditional pond with most of the particles concentrated within the inner pond. Lower velocity and the higher solids retention in the PIP thus allowed for better treatment performance compared to traditional ponds. The findings from this study can be used as preliminary data for future in-depth investigations of the PIP system leading toward effective and optimal designs. This will help address the major societal concern of water scarcity with low-cost and effective wastewater treatment.

A programmable DC power supply with Real-time Digital Simulator (RTDS)-based photovoltaic (PV) Power Hardware-In-the-Loop (PHIL) simulators have been used to improve the control algorithm and reliability of PV Inverter. This paper proposes a supervisory control algorithm for PV PHIL simulator with non-RTDS device that is an alternative solution of high cost PHIL simulator. However, when such a simulator with conventional algorithm which is used in RTDS is connected to a PV inverter, the output is in the transient state and it makes it impossible to evaluate the performance of the PV Inverter. Therefore proposed algorithm controls the voltage and current target values according to the constant voltage (CV) and constant current (CC) modes to overcome the limitation of the Computing Unit, DC power supply and also uses a multi-rate system to account for the characteristics of each component of simulator. A mathematical models of a PV system, programmable DC power supply, isolated DC measurement device and Computing Unit are integrated to form a real-time processing simulator. Performance tests using a PV PHIL simulator which is applied proposed algorithm connected a PV inverter are carried out and proved superiority and utility of this method against conventional methods.

This article explores the relationship between convex functions defined on integers ($\mathbb{Z}$) and their extension to real numbers ($\mathbb{R}$). We introduce key definitions and investigate the hypothesis that there exists a unique convex curve within this family of functions, leading to a proof by contradiction. Our findings highlight the preservation of convexity as functions transition from integers to real numbers.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

This study addresses the central question that how can a precise measurement of the gluon Parton Distribution Function (PDF) be attained, thereby enhancing our understanding of the intricate quark-gluon composition within nucleons? Through a dual approach involving Quantum Chromodynamics (QCD) and high-energy particle collisions, the research combines computational tools and experimental techniques, focusing on protons and neutrons. Scattering experiments and advanced detectors are utilized to probe nucleon structure. Theoretical frameworks like QCD equations and the Momentum Sum Rule investigate Parton Distribution Functions at specific momentum fractions and energy scales. The primary goal is to achieve an accurate measurement of the gluon PDF, crucial for unraveling strong force complexities and internal nucleon dynamics. The study's theoretical plots and equations illustrate hypothetical behaviors of gluon distribution, quark distribution, and splitting functions, contributing to a deeper understanding of fundamental particles.

Most studies on the association of in utero exposure to cigarette smoking and childhood overweight or obesity (OWO) were based on maternal self-reported smoking data and few were based on objective biomarkers. In this study, we evaluated the associations between self-reported and biomarkers of in utero exposure to cigarette smoking with risk of childhood OWO. We analyzed data from 2351 mother-child pairs in the Boston Birth Cohort, a US low-income minority cohort that enrolled children at birth and followed prospectively up to age 18 years. In utero smoking exposure was measured by maternal self-report and by maternal and cord plasma cotinine and hydroxycotinine metabolites. We assessed the individual and joint associations of each smoking exposure measure and maternal OWO with childhood OWO using multinomial logistic regressions. We used nested logistic regressions to investigate the childhood OWO prediction performance when adding maternal and cord plasma biomarkers as input covariates on top of self-reported data. Our results demonstrated that in utero cigarette smoking exposure defined by self-report and by maternal or cord metabolites were consistently associated with increased risk of long-term child OWO. Adding maternal and cord plasma biomarker information to self-reported data improved the prediction accuracy of long-term child OWO risk.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Parental phubbing behavior is a significant factor in predicting adolescent smartphone dependence, but prior research has predominantly focused on a unidirectional perspective from the child's viewpoint, overlooking potential perceptual differences between parents and their children regarding parental phubbing. Therefore, are there differences in the perceptions of parental phubbing between parents and their children? Based on the "Discrepancy-Maladaptive" hypothesis, the presence of perceptual discrepancies in family factors can lead to adverse developmental outcomes in children. Does the parent-child perceptual discrepancy in parental phubbing influence adolescent smartphone dependence? And what role does parent-child relationship play in this context? This study selected 728 families from a middle school in Wuhan, and surveys were administered to both children and parents. The findings reveal: (1) There exist significant parent-child perceptual discrepancies in parental phubbing. (2) Parent-child perceptual discrepancies in parental phubbing significantly positively predict adolescent smartphone dependence and negatively predict parent-child relationships, while parent-child relationships significantly negatively predict adolescent smartphone dependence. (3) The parent-child relationship plays a mediating role between parent-child perceptual differences in parental phubbing behavior and adolescent smartphone dependence.

Legumes develop root nodules that harbour endosymbiotic bacteria, rhizobia. These rhizobia convert nitrogen to ammonia by biological nitrogen fixation. A thorough understanding of the biological nitrogen fixation in legumes and its regulation is key to develop sustainable agriculture. It is well known that plant hormones affect nodule formation; however, most studies are limited to model legumes due to their suitability for in vitro, plate-based assays. Specifically, it is almost impossible to measure the effects of exogenous hormones or other additives during nodule development in crop legumes such as soybean as they have huge root system in soil. To circumvent this issue, the present research develops suitable media and growth conditions for efficient nodule development under in vitro, soil free conditions in an important legume crop, soybean. Moreover, we also evaluate the effects of all major phytohormones during soybean nodulation under identical conditions. This versatile, inexpensive, scalable and simple protocol provides several advantages over previously established methods. It is extremely time-and resource-efficient, does not require special training or equipment, and produces highly reproducible results. The approach is expandable to other large legumes as well as for other exogenous additives.

Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3–205) months. Fifty-nine patients (%59.6) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or &gt;1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.

This paper draws an earlier book (with Evans and Higgins) entitled Bad Call: Technology’s Attack on Referees and Umpires and How to Fix It (hereafter Bad Call) and its various precursor papers. These show why it is that current match officiating aids are unable to provide the kind of accuracy that is often claimed for them and that sports aficianados have been led to expect from them. Accuracy is improving all the time but the notion of perfect accuracy is a myth because, for example, lines drawn on sports fields and the edges of balls are not perfectly defined. The devices meant to report the exact position of a ball – for instance ‘in’ or ‘out’ at tennis – work with the mathematically perfect world of virtual reality, not the actuality of an imperfect physical world. Even if ball-trackers could overcome the sort of inaccuracies related to fast ball speeds and slow camera frame-rates the goal of complete accuracy will always be beyond reach. Here it is suggested that the purpose of technological aids to umpires and referees be looked at in a new way that takes the viewers into account.

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

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

Perception and motor interaction with physical surroundings can be analyzed by the changes in probability laws governing two possible outcomes of neuronal activity, namely the presence or absence of spikes (binary states). Perception and motor interaction with physical environment are accounted partly by the reduction in entropy within the probability distributions of binary states of neurons in distributed neural circuits, given the knowledge about the characteristics of stimuli in physical surroundings. This reduction in the total entropy of multiple pairs of circuits in networks, by an amount equal to the increase of mutual information among them, occurs as sensory information is processed successively from lower to higher cortical areas or between different areas at the same hierarchical level but belonging to different networks. The increase in mutual information is partly accounted by temporal coupling as well as synaptic connections as proposed by Bahmer and Gupta [1]. We propose that robust increases in mutual information, measuring the association between the characteristics of sensory inputs and neural circuits connectivity patterns, are partly responsible for perception and successful motor interactions with physical surroundings. It is also argued that perception from a sensory input is the result of networking of many circuits to a common circuit that primarily processes the given sensory input.

In the energy-momentum density expressions for a relativistic perfect fluid with a bulk motion, one comes across a couple of pressure-dependent terms, which though well known, are to an extent, lacking in their conceptual basis and the ensuing physical interpretation. In the expression for the energy density, the rest mass density along with the kinetic energy density of the fluid constituents due to their random motion, which contributes to the pressure as well, are already included. However, in a fluid with a bulk motion, there are, in addition, a couple of explicit, pressure-dependent terms in the energy-momentum densities, whose presence to an extent, is shrouded in mystery, especially from a physical perspective. We show here that one such pressure-dependent term appearing in the energy density, represents the work done by the fluid pressure against the Lorentz contraction during transition from the rest frame of the fluid to another frame in which the fluid has a bulk motion. This applies equally to the electromagnetic energy density of electrically charged systems in motion and explains in a natural manner an apparently paradoxical result that the field energy of a charged capacitor system decreases with an increase in the system velocity. The momentum density includes another pressure-dependent term, that represents an energy flow across the system, due to the opposite signs of work being done by pressure on two opposite sides of the moving fluid. From Maxwell's stress tensor we demonstrate that in the expression for electromagnetic momentum of an electric charged particle, it is the presence of a similar pressure term, arising from electrical self-repulsion forces in the charged sphere, that yields a natural explanation for the famous, more than a century old, 4/3 factor in the electromagnetic mass.

Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions and ecosystem functions. Endemics and CoEs play a prominent role in nature conservation monitoring and management, and in the organization of zoos, aquaria and botanical gardens. We review the meaning of different groups of organisms and indicators for the characterization of endemic-rich regions, the importance of heterogeneity in space, continuity in time, isolation and ex-situ management for the survival of endemic and threatened species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species concentrated in CoEs. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides or tsunamis. For conservation purposes the management of zoos, aquaria, botanical gardens, of regional land use, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of biodiversity, which is linked with human culture including the management of zoos, aquaria and botanical gardens, aesthetics, wellbeing, health and trade.

The use of Artificial Neural Networks (ANN) is a great contribution to medical studies since the application of forecasting concepts allows the analysis of future diseases propagations. In this context, this paper presents a study of the new coronavirus SARS-COV-2 with a focus on verifying the virus propagation associated with mitigation procedures and massive vaccination campaigns. There were proposed two methodologies to predict 28 days ahead the number of new cases, deaths, and ICU patients of five European countries: Portugal, France, Italy, United Kingdom, and Germany, and a case study of the results of massive immunization in Israel. The data input of cases, deaths, and daily ICU patients was normalized to reduce discrepant numbers due to the countries size, and the cumulative vaccination values by the percentage of population immunized, at least with one dose of vaccine. As a comparative criterion, the calculation of the mean absolute error (MAE) of all predictions presents the best methodology and targets other possibilities of use for the proposed method. The best architecture achieved a general MAE for the 1 to 28 days ahead forecast lower than 30 cases, 0,6 deaths and 2,5 ICU patients by million people.

To support the development of research evidence and behavioral health policy that aligns with the priorities of youth and families serviced in child and youth mental health systems, this project documents the service outcomes that caregivers value most. A diverse group of caregivers, representing six regions of the United States, participated in two rounds of virtual one-hour focus groups. In round 1, participants identified what they hoped to gain from using behavioral health services for themselves, their families, and their child and discussed what made services a positive experience for them. They then reported their top three most hoped for outcomes. In round 2, groups validated and refined summary findings from round 1. Caregivers prioritize service quality outcomes, primarily. They expressed a desire for an accessible, respectful, and supportive treatment environment underpinned by well-trained and culturally responsive professionals. Caregivers also desire seamless cross-sector provider collaboration and care transitions which integrate the insights and preferences of families and children themselves to craft a customized care plan. Priority outcomes not related to service quality included hoping to gain increased knowledge, resources, and tools and techniques to support the mental health needs of their children, help them improve their daily functioning, and develop more effective interpersonal communication skills. Caregivers also reported hoping to experience less stigma related to the mental health needs of their children and to achieve personal fulfillment for themselves and their children. Research and policies should prioritize and be designed to address the outcomes that matter to youth and families.