The Shared Socioeconomic Pathways (SSPs) are the new global development trends that inform global and regional climate change research. They have the potential to foster the integration of socioeconomic scenarios within assessments of future climate-related health impacts. To date, such assessments have primarily superimposed climate scenarios on current socioeconomic conditions only. Until now, the few assessments of future health risks that employed the SSPs have focused on future human exposure—i.e., mainly future population patterns—neglecting future human vulnerability. This paper first explores the research gaps—mainly linked to the paucity of available projections—that explain such a lack of consideration of human vulnerability under the SSPs. It then highlights the need for projections of socioeconomic variables covering the wide range of determinants of human vulnerability, available at relevant spatial and temporal scales, and accounting for local specificities through sectoral and regional extended versions of the global SSPs. Finally, this paper presents two innovative methods of obtaining and computing such socioeconomic projections under the SSPs—namely the scenario matching approach and an approach based on experts’ elicitation and correlation analyses—and applies them to the case of Europe. They offer a variety of possibilities for practical application, producing projections at sub-national level of various drivers of human vulnerability such as demographic and social characteristics, urbanization, state of the environment, infrastructure, health status, and living arrangements. Both the innovative approaches presented in this paper and existing methods—such as the spatial disaggregation of existing projections and the use of sectoral models—show great potential to enhance the availability of relevant projections of determinants of human vulnerability. Assessments of future climate-related health impacts should thus rely on these methods to account for future human vulnerability—under varying levels of socioeconomic development—and to explore its influence on future health risks under different degrees of climate change.

International migration is closely tied to demographic, socioeconomic, and environmental factors and their interaction with migration policies. Using a combination of a gravity econometric model and an overlapping generations model, we estimate the probability of bilateral migration among 160 countries in the period of 1960 to 2000 and use these findings to project international migration flows and their implication for income inequality within and between countries in the 21st century under five shared socioeconomic pathways (SSPs). Our results show that international migration not only increases the welfare in developing countries, but also closes the inequality gap within and between low-skilled and high-skilled labor in these countries. In most developed countries on the contrary, international migration increases the inequality gap and slightly reduces output. These changes are not uniform and vary significantly across countries depending on their population growth and human capital development trajectories. Overall, while migration is strongly affected by inequality between developed and developing countries, it has an ambiguous impact on inequality within and between countries.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders worldwide. Among the symptoms of MDD, sleep disturbance such as insomnia is prominent and the first reason patients may seek professional help. However, the underlying pathophysiology of this comorbidity is still elusive. Recently, genome-wide association studies (GWAS) have begun to unveil the genetic background of several psychiatric disorders, including MDD and insomnia. Identifying the shared genomic risk loci between comorbid psychiatric disorders could be a valuable strategy to understand their comorbidity. This study seeks to identify the shared genes and biological pathways between MDD and insomnia based on their shared genetic variants. First, we performed a meta-analysis based on the GWAS summary statistics of MDD and insomnia obtained from Psychiatric Genomics Consortium and UK Biobank, respectively. Next, we associated shared genetic variants to genes using two gene mapping strategies: (a) positional mapping based on genomic proximity and (b) expression quantitative trait loci (eQTL) mapping based on gene expression linkage across multiple tissues. As a result, a total of 719 shared genes were identified. Over half (51%) of them are protein-coding genes. Functional enrichment analysis shows that the most enriched biological pathways are related to epigenetic modification, sensory perception, and immunologic signatures. We also identified druggable targets using a network approach. Together these results may provide insights into understanding the genetic predisposition and underlying biological pathways of comorbid MDD and insomnia symptoms.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

Shared public buildings have become centers of innovation, integrating advanced technologies to meet evolving societal needs. With a heightened emphasis on occupants’ health and well-being, these buildings serve as hubs for technological convergence, facilitating seamless connectivity and intelligent data analysis and management. Within this context, environmental monitoring emerges as a foundational element, pivotal to all aspects of building management. This article provides findings from the nationally funded RE-START project, which focuses on shared public buildings, with special regard to educational and medical facilities. The project explores enhanced indoor air quality monitoring, focusing in particular on CO2 concentration that is directly correlated with occupancy, as a fundamental element for developing health and safety protocols, energy efficiency strategies, integration of smart building technologies, and data-driven energy management. The intersection of environmental monitoring, energy efficiency, security, and IoT technologies in in indoor spaces are relevant. The outcomes of the study reveal the delicate nature of all the involved components, that need to be carefully developed in an integrated manner.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Objective: (1) Describe the current literature on the relationship between EDS and SEP and (2) provide recommendations for consideration of SEP in sleep medicine and biomedical research. Methods: Databases Medline/Pubmed, Web of Science, Google scholar and Scopus were screened using PRISMA guidelines and 19 articles were included in the final synthesis. Results: All studies were cross-sectional. Among these studies, 21.05% (n = 4) are focused on children and adolescent and the lasting 88.95% (n = 15) focused on adults and old people. Age ranged between 8 and 17 years old for children/adolescent and ranged from 18 until 102 years old for adults. Main SEP measures presented in these studies were education, income, perceived socioeconomic status and employment. Sample size in these studies varied from N = 90 participants until N = 33865 participants. Overall, a lower educational level, a lower income and full-time employment were associated with EDS. EDS symptoms are prevalent in women, especially those with a low income or no job; and children and adolescents with difficult living conditions or people working part-time reported more sleep disturbances. Conclusions: SEP is already considered as an important determinant for many health outcomes, but if SEP is embedded in experimental design in psychosomatic research, biomedical research and clinical practice as a constant variable regardless of outcome; it will move forward future investigations.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

This study provides a detailed investigation into the pathways through which microplastics from urban sources are transported to marine ecosystems, their distribution across different environments, and their impacts on marine life. Utilizing a combination of water and sediment sampling across urban, riverine, and marine environments, the research quantitatively assesses the concentration and types of microplastics present, and evaluates the ecological consequences of their accumulation in marine ecosystems. The findings reveal a significant concentration of microplastics in all examined environments, with the highest levels detected in urban areas, closely linked to industrial activities and inadequate waste management practices. The study documents a variety of microplastic polymers, with polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) being the most prevalent. A substantial impact on marine organisms was observed, including evidence of microplastic ingestion across a wide range of species and indications of stress and physical damage to coral reefs. Seasonal variations indicate that microplastic concentrations peak during periods of high rainfall, suggesting urban runoff as a critical pathway for microplastic transport. The study concludes with recommendations for improving waste management practices, enhancing public awareness and engagement in plastic recycling efforts, and implementing policies aimed at reducing the production and use of single-use plastics. This research underscores the urgent need for coordinated actions to mitigate the pervasive issue of microplastic pollution, highlighting the role of urban management and policy interventions in safeguarding marine ecosystems.

Abstract: This study investigates the transition to sustainable shipping industry within the framework of the IMO's 2050 carbon neutrality objective, focusing on socio-technical systems analysis. The research delves into the sustainable paradigm shift towards alternative marine fuels such as LNG, methanol, ammonia, and hydrogen from a socio-technical transition perspective, analyzing the multi-level per-spective challenges and opportunities. Specifically, it scrutinizes the implications of adopting these al-ternative fuels for global shipping, identifying technical uncertainties, financial constraints, and infra-structure needs. Through a comprehensive review of existing literature on ship emissions and alterna-tive fuels, coupled with socio-technical transition theory, the study addresses the multifaceted chal-lenges and opportunities in meeting the IMO's environmental objectives. It emphasizes the necessity of collaborative governance, innovative niche strategies, and a holistic approach to leverage the current window of opportunity in facilitating the maritime industry's transition to sustainable fuel options. Fi-nally, this research enhances our understanding of the intricate interplay between technological, social, industrial, and cultural dynamics in the greening of shipping and offers insights into the strategic adop-tion of environmentally friendly marine fuels for a sustainable future.

Cisplatin is a widely used anticancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas increased Bcl-2 expression. Moreover, in cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor interacting protein kinase (RIPK) and mixed lineage kinase domain like (MLKL) were identified. In vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted by co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anticancer adjuvant.

Disadvantaged groups around the world have suffered and endured higher mortality during the current COVID-19 pandemic. This contrast disparity suggests that socioeconomic and health-related factors may drive inequality in disease outcome. To identify these factors correlated with COVID-19 outcome, country aggregate data provided by the Lancet COVID-19 Commission subjected to correlation analysis. Socioeconomic and health-related variables were used to predict mortality in the top 5 most affected countries using ridge regression and extreme gradient boosting (XGBoost) models. Our data reveal that predictors related to demographics and social disadvantage correlate with COVID-19 mortality per million and that XGBoost performed better than ridge regression. Taken together, our findings suggest that the health consequence of the current pandemic is not just confined to indiscriminate impact of a viral infection but that these preventable effects are amplified based on pre-existing health and socioeconomic inequalities.

Background: Rapid advancements in Distributed Ledger Technology (DLT), including blockchain, are foundational to a new era of digital innovation. This innovation has catalyzed the emergence of ‘Decentralized Science (DeSci),’ a new concept and movement that aims to address the challenges of modern science. Objective: Given the novelty of the field of DeSci, this study aims to provide a comprehensive definition of the term as well as explore and conceptualize shared values and guiding principles inherent to DeSci. Methods: In line with the objectives of this study, an exploratory literature review was conducted to identify and synthesize the scholarly and secondary literature. The search and selection process included six databases (PubMed, Google Scholar, Web of Science, IEEE Xplore, arXiv, and Social Science Research Network), and the search period was limited to the last 15 years, from 2008 to 2023. To identify relevant secondary literature, such as articles, reports, blog posts, and website content, a keyword search was conducted in three search engines (Google.com, Bing.com, and Yahoo.com). Owing to the novelty of the concept and movement of DeSci, the exploratory literature review was supplemented by an anonymous online-based expert survey using a combination of single-choice and open-ended questions. The experts were selected based on predefined inclusion criteria, in association with their activities in the field of DeSci. The responses to the single-choice questions were subject to statistical analysis, whereas the open-ended questions were analyzed using qualitative content analysis. Results: Seven studies were selected for evaluation as part of the search and selection process to identify relevant scholarly literature. Following the review of secondary literature, additional 24 publications were included in the analysis. In the expert survey, 39 valid datasets were collected and analyzed. Following the synthesis of the results of the exploratory literature review and expert survey, a comprehensive definition of the term ‘Decentralized Science’ (DeSci) was formulated to reflect recurring themes. As no publications that explicitly discussed or addressed the values or principles of DeSci in the exploratory literature review could be identified, a set of shared values and guiding principles for DeSci were defined based on the results of the expert survey. Conclusion: The results of this study underscore the emerging nature of DeSci, as evidenced by the limited availability of relevant information and scarcity of academic publications. While this study proposes a comprehensive definition of DeSci as well as a set of shared values and guiding principles, the results of this study highlight the importance of ongoing evaluation and validation. Furthermore, the results of this study indicate a clear need for future research in the field of DeSci, emphasizing its dynamic and developing nature.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

In this paper, we unite concepts from Husserlian phenomenology, the active inference framework in theoretical biology, and category theory in mathematics to develop a comprehensive framework for understanding social action premised on shared goals. We begin with an overview of Husserlian phenomenology, focusing on aspects of inner time consciousness, namely, retention, primal impression, and protention. We then review active inference as a formal approach to modeling agent behavior, based on variational (approximate Bayesian) inference. Expanding upon Husserl’s model of time consciousness, we consider collective goal-directed behavior, emphasizing shared protentions among agents and their connection to the shared generative models of active inference. This integrated framework aims to formalize shared goals in terms of shared protentions, and to thereby shed light on the emergence of group intentionality. Building on this foundation, we incorporate mathematical tools from category theory; particularly, sheaf and topos theory, to furnish a mathematical image of individual and group interactions within a stochastic environment. Specifically, we employ morphisms between polynomial representations of individual agent models, allowing predictions not only of their own behaviors but also those of other agents and environmental responses. Sheaf and topos theory facilitate the construction of coherent agent worldviews and provides a way of representing consensus or shared understanding. We explore the emergence of shared protentions, bridging the phenomenology of temporal structure, multi-agent active inference systems, and category theory. Shared protentions are highlighted as pivotal for coordination and achieving common objectives. We conclude by acknowledging the intricacies stemming from stochastic systems and uncertainties in realizing shared goals.

This paper presents and discusses the pedagogical implication of teaching Shared Value, presenting a case study about a contamination lab namely the case of the Shared Value Living Lab (SVLL) which took place at the University of Torino (UniTO) in Italy. The paper analyzes the pedagogical side of CSV (arguments, topics, learning methodologies, etc.) in the framework of recent theories and approaches of teaching sustainability in business school and in the cooperation between industry and academia, as well. Our research methodology relies on the analysis and comparison of one case study under an intrinsic as it enables researchers to find “interactivity” and connectedness between the individuals participating. The SVLL case is an interesting example of co-creation of social value between academia and its stakeholders. First, it represents an inclusive project linking society and business; second, SVLL acted as a hub putting in contact different interlocutors; third, SVLL training stimulated the acquisition of soft skill in students (interviews, managing relations, represents the project outside university, explaining the project to people, research curiosity) through contamination activities. With our study, we demonstrate the change in students participating in the SVLL may not only be cognitive but also affective, making students feel hopeful, empowered and liberated, and ready to contribute to a more profound change towards the vast array of pro-sustainability behaviors.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

With the current technological transformation in the automotive industry, autonomous vehicles are getting closer to the Society of Automative Engineers (SAE) automation level 5. This level corresponds to the full vehicle automation, where the driving system autonomously monitors and navigates the environment. With SAE-level 5, the concept of a Shared Autonomous Vehicle (SAV) will soon become a reality and mainstream. The main purpose of an SAV is to allow unrelated passengers to share an autonomous vehicle without a driver/moderator inside the shared space. However, to ensure their safety and well-being until they reach their final destination, it is required an active monitoring of all passengers. In this context, this article presents a microphone-based sensor system that is able to localize sound events inside an SAV. The solution is composed of a Micro-Electro-Mechanical System (MEMS) microphone array with a circular geometry connected to an embedded processing platform that resorts to Field-Programmable Gate Array (FPGA) technology to successfully process in hardware the sound localization algorithms.

Multiple social and environmental justice concerns are linked to urban form such as the distribution of socioeconomic class populations, healthcare spending, air pollution exposure, and human mobility. This study used 1m resolved LIDAR data to characterize land use in Salt Lake County, Utah and associate it with sociodemographic and air quality data at the census block group and zip code levels. We found that increasing tree cover was associated with higher per capita income and lower minority populations while increasing built cover was linked to lower per capita income and higher minority populations. Air quality showed less strong correlations, however, decreased non irrigated cover, increased built cover, and higher amounts of households living under poverty was related to higher long-term PM2.5 exposure. Several policy efforts have been undertaken to improve air quality and reduce negative health outcomes in Utah which are being informed by regulatory and research grade air quality sensors.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Shared micromobility has gained significant attention in the field of transportation engineering in recent years as an environmentally friendly, convenient, and easily accessible transportation mode. Like other medium-sized cities, Birmingham, Alabama implemented a shared micromobility pilot program in 2021 that captured the attention of local travelers. This study examined shared e-scooter usage and associated travel patterns in Birmingham using 2021-2022 field data. From these data, ArcGIS maps were used to showcase trip origins and destinations. To gain a further understanding of e-scooter travel patterns in the study area, zip code and block group densities were calculated. Additionally, a negative binomial regression model was constructed to identify determinants of shared e-scooter trips. The analysis results showed that the usage of shared e-scooters was the highest during the nighttime, on weekends, and in the fall season. Furthermore, the research findings indicated that shared e-scooters experienced their highest utilization rates in areas with a higher proportion of educated and higher-income individuals. These findings suggest that travelers’ mode choice related to the use of micromobility modes is influenced by environmental and demographic factors. Overall, this case study offers valuable contributions to the understanding of the role of shared e-scooters in Birmingham's transportation landscape and can guide transportation authorities in other medium-sized cities in their efforts to plan for micromobility options.

In times of war, civilians experience a heightened risk of exposure to traumatic experiences. This can lead to a greater risk of developing mental health conditions such as post-traumatic stress disorder (PTSD), which can impact individuals and communities. Research suggests that the severity of the reactions to traumatic events is likely to be influenced by the level of exposure to the traumatic events and personal characteristics. This paper examines the correlation between symptoms of Post-Traumatic Stress Disorder (PTSD) and various factors such as the extent of exposure to missile alarms, personal traits, and socioeconomic elements among Israeli civilians impacted by rocket attacks from Hamas. Our specific focus is on the influence of these rocket attacks on Israel's populace during the military operation conducted by the Israeli army, "Guardian of the Walls," in May 2021.Our findings suggest that, typically, individuals who have experienced less exposure to missile attacks and alarms, those belonging to larger families, and those with a higher level of education and income are less prone to experiencing post-traumatic symptoms. The study was carried out using surveys that gathered demographic information about the participants, as well as a specific questionnaire designed to evaluate the presence and extent of post-trauma symptoms.These findings could aid in devising preventative strategies to mitigate the PTSD risk among vulnerable groups. They indicate the importance of considering socio-economic elements when delivering mental health services to those impacted by violent incidents and trauma.

Mobile phones have become an integral part of our lives in the last two decades, leaving a digital trace of our activities and communication. This study aims to develop a data processing framework to evaluate human mobility and socioeconomic status based on call detail records. The methodology proposed first calculates radius of gyration and entropy for each user, then estimates the socioeconomic status by the price and age of the subscribers' phones. Finally, an unsupervised machine learning algorithm was used to group the cells into clusters based on their mobility and socioeconomic metrics. The research showed differences between Buda and Pest during a large scale social event using mobile phone ages and prices. Additionally, the clustering results revealed homogenous groups of cells around Budapest, with similar mobility and socioeconomic metrics. The main conclusion is that mobile network data combined with mobile phone properties offer a useful tool for characterising urban mobility and socioeconomic status.

The first two decades of the 21st-century have seen the emergence of the modern citizen science movement, increased demand for niche eco and wildlife tourism experiences, and the willingness of people to voluntarily share information and photographs online. To varying extents, the rapid growth of these three phenomena has been driven by the availability of portable smart devices, access to the Web 2.0 internet from almost anywhere on the planet, and the development of applications and services, including social media/networking sites (SNSs). In addition, the number of peer-reviewed publications that explore how text and images shared on SNSs can be data-mined for academic research has surged in recent years. This systematic quantitative review has two goals. The first goal is to provide an oversight of how the photographs that ecotourists share online are contributing to wildlife tourism research. The second goal is to promote the emerging photovoice technique as a theoretical context for social research based on the photographs and comments that ecotourists share on SNSs. From the perspectives of community benefits, conservation behaviours, and environmental education, there are many similarities between authentic ecotourism experiences and quality ecological citizen science programs. Much of the literature regarding the theory and practice of citizen science reports on the difficulties of attracting, training, motivating and retaining community members. The synthesis of this review is that crowdsourcing wildlife and tourism data from comments and photographs that ecotourists share on SNSs is a credible method of research that provides a self-replenishing pool of citizen scientists.

Identifying or authenticating a computer user are necessary steps to keep systems secure on the network and to prevent fraudulent users from accessing accounts. Keystroke dynamics authentication can be used as an additional authentication method. Keystroke dynamics involves in-depth analysis of how you type on the keyboard, analysis of how long a key is pressed or the time between two consecutive keys. This field has seen a continuous growth in scientific research. In the last five years alone, about 10,000 scientific researches in this field have been published. One of the main problems facing researchers is the small number of public data sets that include how users type on the keyboard. This paper aims to provide researchers with a data set that includes how to type free text on the keyboard by 80 users. The data were collected in a single session via a web platform. The dataset contains 410,633 key-events collected in a total time interval of almost 24 hours. In similar research, most datasets are with texts written by users in English. The language in which the users wrote for this research is Romanian. This paper also provides an extensive analysis of the data set collected and presents relevant information for the analysis of the data set in future research.

There has been debate recently on how the population in traditional mining areas of Central and Eastern Europe face precarity and marginalization. A spatial approach was employed in a Romanian context using available statistical data on a south Carpathian area (i.e Gorj County), surveys and in-depth interviews with residents in one of the rural communities of Gorj. Our findings highlight that a large number of rural localities in this county are technically, economically, and socially underdeveloped. Many inhabitants face a lack of financial resources and employment opportunities, which has led to the emigration of young people to larger Romanian cities or to other countries. We conclude that in order to avoid a much deeper social and spatial marginalization of local inhabitants, an integrated strategy is needed to target economic and social development, investment in infrastructure and public services, the promotion of employment and training opportunities, and to better integrate local culture and traditions into tourism.

Sleep disorders (SD) have a complex aetiology, and socioeconomic status (SES) as determined by social class, household income, ethnicity and education plays an important role in their development. As SD are associated with cognitive impairment and mood disorders, they in turn impact SES. Socioeconomic status also influences allostatic load caused by chronic accumulation of stress throughout life. Environmental and psychological stressors have a direct effect on SD, and they are modulated by SES, in combination with comorbidities like obesity and cardiovascular disease. This review explores the recent theories about the influence of SES on the development of SD in the general population, whether or not occurring with comorbidities, and also focusses on the interplay between socioeconomic status, circadian rhythms, aging and clinical outcomes like metabolic diseases and cancer.

This paper presents an approach to teacher identity heritage as result of the implementation of a research device created through Arts-based Research (ABR) methods, specifically with video elicitation and video essay used as research tools. Two main objectives were raised. The first one, to establish the real relevance of focusing performance on teacher identity. The second one, testing a new methodological proposal specifically designed for this purpose, but still useful in other contexts where heritage identity is as present as in teaching. The device, Body-camera, involves a process that allows new ways to understand the creation of identities using video to encourage the production of new meanings by visual and oral data. The participants were teachers in training during their internship period. Some notions about teachers' identity heritage were revealed, and also preserved, firstly, through personal perspectives by video elicitations and secondly, through collective perspectives by video essays. Both are video structures used in ABR which mix creative experience, memories, life experiences, relationships and links that shape the teachers’ professional identity.

To contain and mitigate the coronavirus (COVID-19) pandemic, African governments have implemented non-pharmacological interventions (NPIs), such as imposing travel bans, confining people to their homes and closing schools, shops and workplaces. These NPIs are likely to be less effective in circumstances where people need to leave their homes to work, collect food, water and cooking fuel or where people cannot maintain distancing due to overcrowded living environments. Using data from the nationally representative South African General Household Survey 2019, we examined individuals’ vulnerability to the risk of COVID-19 infection due to their health, socioeconomic and living circumstances. We explored socioeconomic-related inequalities in COVID-19 using concentration curve and concentration index methods. Our results showed that vulnerability to COVID-19 was disproportionately concentrated among those with low socioeconomic status. Using the Recentered Influence Function decomposition approach, we found that higher income and education had a significant and positive impact on reducing socioeconomic-related COVID-19 vulnerability. Conversely, people with lower socioeconomic status were more likely to live in circumstances that made compliance with NPI requirements almost impossible, and they were also more likely to have pre-existing health conditions that made them more vulnerable to COVID-19.

Nowadays one of the issues interesting for researchers of political, social, and economic sciences is to investigate immigration from different angles. Accordingly, they use a diverse range of instruments, different types of graphs, descriptive indices and complex mathematical models. Immigration has always been one of the paths helping humans in their own efforts for getting compatible with the environment and coping with difficulties. Nevertheless, if this issue has been considered as an instrument regulating resources and species automatically, in the present era, its negative aspects have been evident and socioeconomic consequences of immigration in the framework of development economy and security has attracted scholars’ attentions. One of the countries attracting for immigrants particularly in the continent of Africa is South Africa. Statistics indicates that this country is the most attractive one for refugees. Somalis are one of the most important and largest groups seeking refuge in South Africa because they are usually merchants who earn money in the poor places. However, business in the poor places endangers their lives and properties because of high rate of crimes and xenophobia. As a result, the target countries face a lot of socioeconomic and security problems. The present study tries to investigate the issue of Somali immigration using network models.

We investigated preschool-aged children’s understanding of early fractional tasks and how that performance correlates with fine motor skills and use of gestures while counting. Participants were 33 preschoolers aged 4 to 5 in two Southeastern public elementary schools. Children were tested individually in an interview-like setting. Mathematics tasks were presented in a paper and pencil format and the Grooved Pegboard test assessed fine motor skills. Finally, utilization of gestures was evaluated by taking a behavioral rating of the child’s hand morphology, accuracy of gestures, and synchrony of gestures and spoken word while performing a counting task. Results indicate performance on fractional reasoning tasks significantly predicts both fine motor ability and accuracy of gestures.

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

Non-pharmacological interventions in the fight against COVID 19 include: a) suppression, which facilitates its extinction; and b) mitigation, which reduces its speed of spread. Left unmitigated, the intensive care unit bed capacity (ICU) is exceeded over its maximum supply, resulting in increased deaths. Suppression has shown in simulation models the potential for decreasing ICU occupation below its surge limit, effectively decreasing mortality. However, for avoiding a rebound in transmission, suppression must be maintained intermittently until a vaccine is available (which may take up to 2 years). The objective of this paper was to describe the mortality patterns observed in Spain, Italy and South Korea for discussing a hypothetical combined public health policy and socioeconomic model that could potentially reduce mortality while reducing the economic impact of this pandemic in Spain. The plan is based on a progressive-voluntary reinstatement to work of the population exposed to the lowest risks (healthy non-immune family units <50 y/o and immune population) and it depends on having sufficiently available ICU beds for providing adequate support. This model, if proven correct for Spain, could eventually be followed by other countries facing a similar impact of the present pandemic.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. SES can influence global health trajectory for an individual or a community, depending if SES is low or high. Sleep is sensitive to environmental stimuli, as well as living conditions. Plenty of studies linked sleep complaints with mood disorders, allostatic load or circadian disruption; but very few or none investigated deeply what happened earlier to sleep depending of SES. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. Even if recent evidence suggested that few of SES indicators like occupational status are linked with sleep disturbances, the relation between SES and health in general with sleep as an outcome or a mediator is not well documented. This scoping review synthetized studies which investigated physiological and psychological mechanisms resulting from a low SES and linked them with sleep disturbances as consequences or as mediators. This review also explore a possible role played by sleep in the relation between socioeconomic status and health inequalities.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in treatment of PNETs at advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events which are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNET and commonly occurring, and therefore more extensively studied, malignancies. Finally, we will offer perspective on the future research direction of PNET epigenome and its potential applications in patient care.

Euglenids are a group of algae of great interest for biotechnology, with a large and complex metabolic capability. To study the metabolic network, it is necessary to know the subcellular locations of the component enzymes, but despite a long history of research into Euglena, the subcellular locations of many major pathways are only poorly defined. Euglena is phylogenetically distant from other commonly studied algae, they have secondary plastids bounded by three membranes, and they can survive after destruction of their plastids. These unusual features make it difficult to assume that the subcellular organization of the metabolic network will be equivalent to that of other photosynthetic organisms. Moreover, we show here that the presence of the secondary chloroplast means that it is not possible to make reliable predictions of the subcellular locations of enzymes in Euglena using existing informatics tools. In order to generate a model of the central metabolic pathway operating in Euglena we analysed biochemical and proteomic information from a variety of sources to assess the subcellular location of relevant enzymes. We use these assignments to propose the compartmentation of the core metabolic pathways in Euglena, a prerequisite for the further study of the metabolic network of Euglena. This model of the metabolic network shows that, other than photosynthesis, all major pathways present in the chloroplast are duplicated elsewhere in the cell, and that several biosynthetic pathways confined to plastids in higher plants are localized elsewhere in Euglena. Our model demonstrates how this organism can synthesise all the metabolites required for growth from simple carbon inputs, and can survive in the absence of chloroplasts.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

Public transportation scheduling aims to optimize the allocation of transportation resources, enhance transportation efficiency, and increase passenger satisfaction, which is crucial for building a sustainable urban transportation system. As a complement to public transportation, shared bikes provide users with a solution for the last mile of travel, compensating for the lack of flexibility in public transportation and helping to improve its utilization rate. Due to the characteristics of shared bikes, such as peak usage periods in the morning and evening and significant fluctuations in demand across different areas, the optimization of shared bike dispatch can better meet user needs, thereby reducing vehicle vacancy rates and increasing operating revenue. Addressing this issue, this paper designs a comprehensive decision-making approach for spatio-temporal demand prediction and bike dispatch optimization. For demand prediction, we designed a T-GCN based bike demand prediction model. In terms of dispatch optimization, we considered factors such as dispatch capacity, distance restrictions, and dispatch costs, and designed an optimization solution based on genetic algorithms. Finally, this paper validates the approach using shared bike operating data, shows that T-GCN can effectively predict short-term demand for shared bikes. Meanwhile, the optimization model based on genetic algorithms provides a complete dispatch solution verifying the model’s effectiveness. The shared bike dispatch approach proposed in this paper, which combines demand prediction with resource scheduling. This scheme can also be extended to other transportation scheduling problems with uncertain demand, such as store replenishment delivery and intercity inventory dispatch.

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

Eating disorder (ED) symptoms often co-occur with nonsuicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. One hundred and five community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI.

Background and Aims: The present study analyzed retrospectively the association between socioeconomic deprivation and graft and patient survival in a cohort of 2,568 adult recipients of a liver transplant between 1996 and 2022. Materials and methods: The primary exposure was a nationally validated socioeconomic deprivation index (DI) at census block level and ranking from 1-5, with higher ranks indicating more significant socioeconomic deprivation. Results: At a median (IQR) follow-up of 144.8 (204) months, the overall patient and graft survival rates were 92% and 90.4% at 1 year, 78.4% and 72.2% at 5 years, and 58% and 56.7% at 10 years. Recipients with a DI rank above the median (i.e., more deprived) had 1, 5, and 10-year patient and graft survival rates of 91% and 89.5%, 70.4% and 68.4%, 48% and 46.7%, respectively, versus 92% and 90.4%, 78.4% and 72.2%, and 58% and 56.7% for less deprived patients (log-rank p<0.001). More deprived patients had a higher risk of death (p<0.0001), hypertension (p<0.0001), obesity (p=0.02), diabetes mellitus (p=0.02), graft rejection (p<0.0001), chronic kidney dysfunction (p<0.0001), major cardiovascular events (p<0.0001) and de novo malignancies (p<0.0001) than less deprived recipients. The factors associated with the survival probability were younger donor and recipient ages (p=0.03 and 0.02, respectively), female recipient sex (p=0.04), absence of HCV (p<0.01), absence of HCC (p=0.02), absence of DM at transplantation (p=0.03) and 1 year (p=0.01), lower DI (p=0.02), lower MELD (0.02), shorter CIT (p=0.03), TAC (p=0.01), and EVR in the immunosuppressive regimen (p=0.02). Conclusions: Patients from more deprived areas have a higher risk of death after liver transplantation. Pre- and post-transplant socioeconomic risk profiling is warranted to better tailor care to patient’s needs and expectations.

The global rising demand for exploiting limited shared groundwater resources, coupled with significant water deficit, especially in arid and semi-arid regions, has led to escalating conflicts among stakeholders. As such, using Bankruptcy Theory methods can be an appropriate response to the reallocation of resources. This study introduces a novel approach to weighted Bankruptcy, where the relative importance of stakeholders is determined by their contributions to sustainable development, and the impact of their claims on the shared groundwater resources is considered. The framework is implemented in a two-level bankruptcy process including the plains and their beneficiaries (agriculture, drinking and industry). The proposed two-level weighted bankruptcy process applies to the Neyshabour-Ataiyeh-Sabzevar plains in Iran. The process is implemented for two scenarios including the Baseline scenario related to the present status of demands and the Future scenario associated with the estimated demands for the year 2041. To compare the weighted proposed method with the other weighted methods such as Proportional (WPRO), Constrained Equal Awards (WCEA), Pinile (WPIN), Talmud (WTAL), Constrained Equal Losses (WCEL), Modified Constrained Equal Losses (MWCEL), two categories including the deficit-based and resource-based approaches are considered. According to the stability analysis using the Bankruptcy Allocation Stability Index (BASI) method, among the deficit-based methods, the novel approach is chosen as the preferred method for the beneficiaries’ reallocation like the Sabzevar’s beneficiaries. Accordingly, it allocates 86.95%, 10.86% and 2.17% of the shared resource to the agricultural, drinking, and industrial demands, respectively. Among the resource-based methods, the WPIN method is selected for reallocation between the stakeholders and their beneficiaries in each level and scenario of reallocation. The novel approach offers a promising solution to the water resource reallocation problem, ensuring a more equitable and sustainable management of shared groundwater resources.

The accessibility of public transportation is also known as the last mile problem, and it is one of the main obstacles that affect travelers to choose public transport. Although autonomous vehicles (AVs) have made much progress, they have not been officially put into commercial use. This paper adopts stated preference experiments to explore the impact of shared AVs on train trips’ last-mile travel behavior and takes Wuhan as an example for case analysis. First of all, this paper establishes a structural equation model (SEM) based on the theory of planned behavior to explore the latent psychological variables, including travelers’ attitudes (ATTs), subjective norms (SNs), perceived behavior control (PBC), and behavioral intention to use (BIU) toward AVs. These latent psychological variables are incorporated into the latent class (LC) logit model to establish a hybrid model to study the factors and degree of influence on the travel mode choice for the last mile of train trips. The results show that travelers have preference heterogeneity for the travel mode choice of the last mile of train trips. Through the analysis of LCs, education, career, and income significantly impact the classification of LCs. The latent psychological variables towards AVs have a significant impact on the travel behavior of respondents, but the impacts vary among different segments. Elastic analysis results illustrate that a 1% increase in the travel cost for shared AV in segment 1 leads to a 7.598% decrease in the choice probability of shared AV. Respondents from different segments vary significantly in their willingness to pay, and the value of travel time for high-income groups is relatively higher.

This paper has designed a four-channel wide dynamic microwave rectifier circuit for the shortcomings of uneven output voltage of each branch of the multi-channel rectification technology. A voltage-doubling rectifier circuit with identical structure was used in each branch. The four rectifier branches shared the same load at the output terminal, allowing the rectifier circuit to have an RF-DC conversion efficiency greater than 50% over the input power range from 12mW to 274mW, widened by 274% compared to a single channel. Not only the advantages of multi-channel technology with wide dynamics were retained, but also the output voltage was highly consistent and could be directly output in parallel without complex power electronics conversion.

This study investigates the intricate relationship between Venezuelan migration and urban growth in Colombia from 2018 to 2021. The study employs remote sensing data and social network metrics to uncover migration patterns and their impact on urban expansion. The methodology consists of three stages. Firstly, nighttime satellite imagery is used to analyze year-over-year urban growth in Colombia. Secondly, social network data estimates Venezuelan migration, overcoming challenges of underreporting and informal border crossings. Lastly, an econometric analysis explores the quantitative link between Venezuelan migration and urban growth, integrating socioeconomic variables to address endogeneity. The findings reveal the complex interplay of Venezuelan migration, socioeconomic factors, and urban growth. The study outlines remote sensing analysis, introducing the Anthropogenic Footprint Expansion Index (AFEI) to quantify urban growth. Facebook API data estimates migration trends and explores socioeconomic impacts on urban expansion. The analysis uncovers migration, poverty, aging, and urban population proportion as key factors affecting Colombia's urban landscape. Furthermore, the research underscores how Venezuelan migration affected short-term urban expansion pre- and post-COVID-19. Migration had a notable effect before the pandemic, but this influence waned afterward. The study highlights migration's short-term nature and emphasizes age demographics' role in medium-term dynamics.

Aquaculture production is under pressure to increase its production to meet the growing demand for food from a growing population. In the Philippines, aquaculture has experienced the shift from milkfish to prawn with its attractive marketable price. Its intensification has led to negative and positive impacts making its collapse inevitable in the mid-1990s and raised a range of environmental and socioeconomic problems. This paper reviewed the environmental impacts, challenges, and disease outbreaks that overtook the industry using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We examined gaps and changes required to revitalize the industry to properly take-off. It considers and gives details on the impacts of shrimp culture on the environment e.g. shrimp farm management, marine pollution, disease outbreaks, climate change impacts, and socioeconomic impacts. Moreover, the presence of viral diseases such as White Spot Syndrome Virus (WSSV), Monodon Baculovirus (MBV), Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV), Hepatopancreatic Parvovirus (HPV), and Yellow Head Virus (YHV), have caused socioeconomic impacts with approximate losses of 40,080 mt in 1997 to 51,000 mt in 2014 in the shrimp industry. Recommended strategies were considered to improve the environmental management of shrimp aquaculture, including disease management, and priorities that were highlighted for future research. This management relates to adopting good aquaculture practices on shrimp culture, proper environmental monitoring and sustainable practices at the farm level.

MIGAL – Galilee Research Institute is a regional R&amp;D center in the northeast peripheral region of Israel. An internationally recognized applied research institute, MIGAL specializes in biotechnology and computational sciences, plant sciences, precision agriculture and environmental sciences, as well as food, nutrition and health. Most of MIGAL’s researchers serve as the core faculty at Tel Hai Academic College (TH). Despite the country’s small surface area, socioeconomic inequality in Israel is high by OECD standards, with wage differences between rich and poor regions reaching up to 400%. The aims of this study are to identify possible socioeconomic impacts of MIGAL–TH on the peripheral northeast’s development. We discuss the effects of academic research and institutions of higher education on mitigating differences between the center and periphery of the country. Data for MIGAL, TH and the northeastern peripheral region were collected from the yearly reports of the two institutions and the Israel Central Bureau of Statistics. MIGAL was found to serve as a link between research, academic teaching and socioeconomic development in the northeast periphery. Several variables related to this link and describing MIGAL–TH and northeastern periphery development were analyzed over time: MIGAL’s budget, total number of employees and number of employees with PhDs; number of TH graduate students; socioeconomic index (SEI) of the northeastern periphery and its position on the Israeli list of regional SEIs. The signs and significance levels of their trends indicate a potential socioeconomic impact of academic research and higher education on peripheral development in the northeast of the country. Research budgets and the creation of jobs for academics living in the region are just a few examples of this impact.

Investigating and classifying sentiments of social media users (e.g., positive, negative) towards an item, situation, and system are very popular among the researchers. However, they rarely discuss the underlying socioeconomic factor associations for such sentiments. This study attempts to explore the factors associated with positive and negative sentiments of the people about reopening the economy, in the United States (US) amidst the COVID-19 global crisis. It takes into consideration the situational uncertainties (i.e., changes in work and travel pattern due to lockdown policies), economic downturn and associated trauma, and emotional factors such as depression. To understand the sentiment of the people about the reopening economy, Twitter data was collected, representing the 51 states including Washington DC of the US. State-wide socioeconomic characteristics of the people (e.g., education, income, family size, and employment status), built environment data (e.g., population density), and the number of COVID-19 related cases were collected and integrated with Twitter data to perform the analysis. A binary logit model was used to identify the factors that influence people toward a positive or negative sentiment. The results from the logit model demonstrate that family households, people with low education levels, people in the labor force, low-income people, and people with higher house rent are more interested in reopening the economy. In contrast, households with a high number of members and high income are less interested to reopen the economy. The accuracy of the model is good (i.e., the model can correctly classify 56.18\% of the sentiments). The Pearson chi2 test indicates that overall this model has high goodness-of-fit. This study provides a clear indication to the policymakers where to allocate resources and what policy options they can undertake to improve the socioeconomic situations of the people and mitigate the impacts of pandemics in the current situation and as well as in the future.

E-scooters are a micromobility transportation option for completing short trips. In recent years, many ‎cities welcomed shared e-scooters in an effort to offer more mode choices, increase travelers' ‎convenience, and reduce automobile use in their service areas. However, a knowledge gap still remains ‎regarding the acceptability of shared e-scooters as a transportation option, which motivates additional ‎research on user and non-user preferences and attitudes toward e-scooter use. This study investigates ‎latent variables impacting the adoption of shared e-scooters in urban areas, focusing on mode choice ‎factors and attitudes towards e-scooter use and car use. The study utilizes machine learning (ML) ‎techniques and SHAP analysis to analyze survey data (N=1196) collected from travelers in Washington, ‎D.C., Miami, FL, and Los Angeles, CA, in 2021 and 2022. A comparative analysis is performed to develop ‎comprehensive demographic profiles of e-scooter users. The analysis reveals gender (male), age (25-39 ‎years age group), higher income, and educational background as the most relevant factors toward e-‎scooter use. Attitudinal variations among e-scooter users and non-users underscore the complexity of ‎perceptions toward e-scooter use, with significant differences in mode choice factors and attitudes ‎toward the use of e-scooters and private vehicles. Notably, educational background ranked as a significant ‎factor in Washington, D.C., and Miami, while Factor 3, derived from factor analysis and encompassing car ‎use attitudes and the utilization of technology, emerged as influential in Los Angeles. This research ‎contributes fresh insights into factors shaping e-scooter adoption, offering a foundation for informed ‎urban transportation planning and policymaking. The holistic approach showcased in this study enhances ‎understanding of shared micromobility and its implications for urban mobility.

Facing the charging difficulties of free-floating shared electric vehicle and the high cost of mobile charging for single demand, this article proposes a collaborative charging planning method based on the complementary advantages of fixed charging stations and mobile charging vehicles, which can charge shared electric vehicles more efficiently and reduce the charging cost at the same time. A bi-level programming model for fixed and mobile cooperative charging is constructed. The upper level of the model is the minimization model of system charging total cost, seeking the optimal charging scheme and the number of mobile charging vehicles. The lower model is a fixed and mobile cooperative charging path planning model, which calculates the optimal routes for mobile charging vehicles and the shared electric vehicles that need to be transferred to the fixed charging station. The example results show that the cost of the proposed fixed-mobile cooperative charging scheme is reduced by 12.6% compared with the pure fixed charging scheme and 14.9% compared with the pure mobile charging scheme

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

Nowadays, determining the socioeconomic factors' influence on environmental quality is a crucial issue for policymakers. We aim to explore the impact of socioeconomic factors i.e., ethnic conflicts inform ethnic fragmentation, institutions quality effectiveness, and energy consumption on environmental quality by testing the various hypotheses (Pollution Halo Hypothesis, IPAT, and EKC) in 40 selected Asian countries throughout 1993-2019. We also use a set of control variables which are gross domestic product per capita, foreign direct investment inflows, and population growth to determine their impact on environmental quality. We use the Panel Quintile Regression Method of 0.25, 0.5, and 0.75 to analyze the results. We find ethnic conflict negatively affects the environmental quality at all quantiles. The institution's variables regulatory quality and rule of law negatively influence the environmental quality. Our result supports Porter's hypothesis because the effect of direct foreign investment on the amount of CO2 emissions is negative and significant at 0.25, 0.5, and 0.75 quantiles which states that foreign direct investment in the host country supports environmental quality. Furthermore, our results support the IPAT hypothesis in selected Asian countries.

Finding the key factor and possible "Newton's laws" in financial markets has remained the central issue in this area. However, with the development of information and communication technologies, financial models are becoming more and more realistic but complex which is contradictory to the objective law “Greatest truths are the simplest”. Therefore, this paper attempts to discover the most critical parameter and establishes an evolutionary model which is independent of micro features. In the model, information is the only key factor and stock price is the emergence of the collective behavior. The statistical properties of the model are significantly similar to the real market. It also explains the correlations of stocks within an industry, which provide a new idea for the study of key factors and core structures in the financial market.

In recent years, autonomous robots have proven capable of solving tasks in complex environments. In particular, robot manipulations in activities of daily living (ADL) for service robots have been in wide use. However, manipulations such as loading a dishwasher or folding laundry are difficult to automate robustly. In addition, manipulations of grasping multiple objects in domestic environments present difficulty. To perform those applications better, we developed robotic systems based on shared autonomy by combining the cognitive skills of a human operator with autonomous robot behaviors. In this work, we present techniques for integration of a shared autonomy system for assistive mobile manipulation and new strategies to support users in the domestic environment. We demonstrate that the robot can grasp multiple objects with random size at known and unknown table heights. Specifically, we developed three strategies for manipulation. From experimental results, we observed that the first strategy has the highest success rate (70% for random objects) up to 70 cm table height. Two other strategies perform better for 80 cm to 100 cm table height. The success rate of the second and third strategies shows an average 63.3% and 73.3%, respectively, for grasping random objects. We also demonstrated these strategies using two intuitive interfaces, a visual interface in rviz and a voice user interface with speech recognition, which are suitable for elderly people. In addition, the robot can select strategies automatically in random scenarios, which make the robot intelligent and able to make decisions independently in the environment. We obtained interesting results showing that the robot adapts to the environmental variation automatically. After these experimental demonstrations, our robot shows the capabilities for employment in domestic environments to perform actual tasks.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

Shared e-scooters are gaining popularity as a solution for first and last-mile connectivity in urban areas. This study conducted in Doha, Qatar, aimed to understand how weather and land use patterns affect e-scooter usage, utilizing various datasets. Given the novelty of micromobility systems in Qatar and their sensitivity to the local hot and humid climate, the study employed a comprehensive analytical approach. Analysis revealed that e-scooter demand spikes on weekends, particularly in the afternoon. Influential land use factors include proximity to universities and employment centers, while a higher presence of Qatari females in an area correlates with reduced usage, pointing to cultural influences. Weather conditions, especially humidity and extreme temperatures, significantly impact e-scooter demand. The study employed the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm for trip clustering and the Random Forest (RF) algorithm to model trip counts, considering temperature and humidity. Insights showed humidity as a critical predictor of hourly e-scooter trip counts. These findings underscore the importance of considering weather, land use, the relationship between land use characteristics and weather variations, and finally cultural factors in optimizing e-scooter services. By integrating data analysis and machine learning, the study offers valuable insights for enhancing urban mobility and transportation planning in GCC countries, promoting sustainable urban mobility.

The deployment of Artificial Intelligence (AI) systems in decentralized environments is on the rise, yet representation of shared conceptualization in such scenarios remains a challenging issue. The absence of a shared understanding can lead to suboptimal performance of AI systems and hinders the ability to comprehend the knowledge and beliefs of agents in the domain. This paper proposes a formal model for modeling conceptualization in AI systems that integrates ontology, epistemology, and epistemic logic. The model aims to address the gap in representing shared conceptualization in decentralized environments and enhance the performance of AI systems operating in such environments. The proposed model is a hybrid structure that blends extensional and intensional structures and leverages logic-based languages for modeling purposes. A case study in the healthcare sector is presented to illustrate the application of the proposed model. The study contributes to the existing literature by providing a formal model for representing shared conceptualization in decentralized environments, which can be utilized to optimize the performance of AI systems in these environments.

This paper examines the condition of the Scheduled Castes in India and recognizes the factors that are causing dismal performance of the Scheduled Castes despite reservation policies. The paper first discusses the condition of Scheduled Castes based on the parameters of social, economic, education, and political representation. It then provides a brief overview of the current reservation percentages allocated to Scheduled Castes in various sectors. Moreover, the paper explores the causes for the dismal performance of Scheduled Castes despite the existence of reservation policies. In order to improve the condition of Scheduled Castes, the paper proposes a multifaceted approach, including the consideration of socio-economic criteria for recognizing castes in the list of Scheduled Castes, dis reservation of affluent Scheduled Caste families, preferential appointment of Scheduled Castes in administrative positions within Scheduled Areas, and reforms within the National Commission for Scheduled Castes. The paper also emphasizes the importance of periodic evaluations of socioeconomic conditions, talent identification, and grassroots awareness campaigns as strategies to uplift the Scheduled Castes.Keywords

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

Archaea are an essential class of gut microorganisms in humans and animals. Despite the substantial progress in gut microbiome research in the last decade, most studies have focused on bacteria, and little is known about archaea in mammals. In this study, we investigated the composition, diversity, and functional potential of gut archaeal communities in pigs by re-analyzing a published metagenomic dataset including a total of 276 fecal samples from three countries: China (n=76), Denmark (n=100), and France (n=100). For alpha diversity (Shannon Index) of the archaeal communities, Chinese pigs were less diverse than Danish and French pigs (P<0.001). Consistently, Chinese pigs also possessed different archaeal community structures from the other two groups based on the Bray-Curtis distance matrix. Methanobrevibacter was the most dominant archaeal genus in Chinese pigs (44.94%) and French pigs (15.41%), while Candidatus Methanomethylophilus was the most predominant in Danish pigs (15.71%). At the species level, the relative abundance of Candidatus Methanomethylophilus alvus, Natrialbaceae archaeon XQ INN 246, and Methanobrevibacter gottschalkii were greatest in Danish, French, and Chinese pigs with a relative abundance of 14.32%, 11.67%, and 16.28%, respectively. In terms of metabolic potential, the top three pathways in the archaeal communities included the MetaCyc pathway related to the biosynthesis of L-valine, L-isoleucine, and isobutanol. Interestingly, the pathway related to hydrogen consumption (METHANOGENESIS-PWY) was only observed in archaeal reads, while the pathways participating in hydrogen production (FERMENTATION-PWY and PWY4LZ-257) were only detected in bacterial reads. Archaeal communities also possessed CAZyme gene families, with the top five being: AA3, GH43, GT2, AA6, and CE9. In terms of antibiotic resistance genes (ARGs), the class of multidrug resistance was the most abundant ARG, accounting for 87.41% of archaeal ARG hits. Our study reveals the diverse composition and metabolic functions of archaea in pigs, suggesting that archaea might play important roles in swine nutrition and metabolism.

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Objective: The aim of study is to find key genes and enriched pathways associated with lung cancer. Participants and Methods: Differentially expressed genes (DEGs) data of 54674 genes based on stage, tumor and status of lung cancer was taken from 66 patients of African American (AAs) origin. 2392 DEGs were found based on stage, 13502 DEGs were found based on tumor, 2927 DEGs were found based on status having p value (p<0.05). Results: Total 33 common DEGs were found from stage, tumor and status of lung cancer. Gene ontology (GO) and KEGG pathway enrichment analysis was performed and 49 significant pathways were obtained, out of which 10 pathways were found to be exclusively involved in lung cancer development. Protein-protein interaction (PPI) network analysis found 69 nodes and 324 edges and identified 10 hub genes based on their highest degrees. Module analysis of PPI found that ‘Viral carcinogenesis’, ‘pathways in cancer’, ‘notch signaling pathway’, ‘AMPK signaling pathways’ had a close association with lung cancer. Conclusion: These identified DEGs regulate other genes which play important role in growth of lung cancer. The key genes and enriched pathways identified can thus help in better identification and prediction of lung cancer.

Early education is critical for improving energy efficiency. The purpose of this study is to explore the feasibility of Interactive Cross-Border Classes to increase awareness of energy efficiency among middle school students. We designed and tested an Interactive Cross-Border class between Chilean and Peruvian 8th-grade classes. The classes were synchronously connected and all students answered open-ended questions on an online platform. Some of the questions were designed to check conceptual understanding while others asked for suggestions of how to develop their economies while keeping CO₂ air concentration at acceptable levels. In real-time, the teacher reviewed the students’ written answers and the concept maps that were automatically generated based on their responses. Students peer-reviewed their classmates’ suggestions. This is part of an Asia-Pacific Economic Cooperation (APEC) STEM Education project on Energy Efficiency using APEC databases. We found high levels of student engagement, where students discussed not only the cross-cutting nature of energy, but also its relation to socioeconomic development and CO₂ emissions, and the need to work together to improve energy efficiency. In conclusion, Interactive Cross-Border classes are a feasible educational alternative, with potential as a scalable public policy strategy for improving awareness of energy efficiency among the population.

The aim of this work is to explain the behaviour of the multiresistance percentage of Pseudomona aeruginosa in some countries of Europe through a multivariate statistical analysis and machine learning validation, using data from the European Antimicrobial Resistance Surveillance System, the World Health Organization and the World Bank. First, we will use a descriptive analysis and a principal components analysis. Then, we use a k-means clustering to determine the countries and regions that are most affected by the antibiotic resistance. Second, we expand the database by adding some socioeconomic, governance and antibiotic-consumption variables. We then run a data panel regression analysis to determine some functions that relates the multiresistance percentage with those new variables. Finally, we use machine learning techniques to validate a pooling panel data case, using XGBoost and random forest algorithms. The results of the data panel analysis indicate that the most important variables for the multiresistance percentage are corruption control and the rule of law. Similar results are found with the machine learning validation analysis, where the human development index is an additional important variable for the multiresistance percentage.

Background: Shared value creation in Base of the Pyramid (BoP) communities is a crucial process towards building sustainable societies. BoP communities in developing countries represent more than four billion people who live on low incomes with limited access to basic products and services. Current or emerging technologies offer promising solutions for organisations pursuing manufacturing opportunities in BoP communities. This study seeks to explore the literature on how BoP communities may become active participants in sustainably manufacturing products using micro-manufacturing factories. The research question posed is: What are the core concepts that need to be taken into consideration for creating shared value through micro-manufacturing factories in BoP communities? Method: A Systematised Literature review (SLR) was completed following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) method for data selection criteria and analysis. The SLR is used to explore the state of literature with regards to creating manufacturing shared value in BoP communities with the objective to identify study gaps and to explore shared value creation concepts. Results: Literature indicates BoP initiatives that have pursued to engage BoP communities through various innovation strategies. The findings of the review is organised under three strategic pillars: Capability building strategy, Implementation process, and Growth strategy. The capability building strategy defines the users’ intention to create shared value in BoP communities with Micro-manufacturing factories (MMF). It is followed by the implementation process which guides the users to create manufacturing shared value in BoP communities. This is followed by a growth strategy to scale for impact.

Aim: Reporting 3 year outcomes of a community shared care scheme run by specialised independent prescribing (IP) optometrists for stable glaucoma and ocular hypertension (OHT) patients in West Kent, England. Purpose: Shared Care Schemes for glaucoma exist to alleviate the burden on Hospital Eye Services (HES) glaucoma clinics. We studied the effectiveness of community care by highly trained and qualified IP optometrists in terms of disease stability and referral rate into HES.Methods: Retrospective longitudinal review of 200 eyes with stable early to moderate stage glaucoma and OHT followed-up in two specialist optometry practices. Outcome measures included visual field mean deviation (VFMD), intraocular pressure (IOP), changes to treatment and referral rate into HES. Inclusion criteria included all patients with OHT and glaucoma (open angle and primary angle closure) referred for community follow-up. Incomplete data sets were excluded.Results: Mean age 71yrs (range 28 - 93yrs) and equal male: female ratio. n= 159 at year 3. The results for both outcomes showed no significant change from baseline at 12 or 24-month time points. However, a significant change from baseline at 36 months was observed for both outcomes: mean reduction of 0.7 mmHg in IOP, and a mean reduction of 0.3 dB in VFMD. There was a statistically significant change in the number of drops used at 36 months (p=0.001). 11 patients had a change in medication within 3 years. One patient was referred back to HES for uncontrolled IOP and consideration of trabeculectomy.Conclusion: Community follow-up of stable cases of glaucoma and OHT by highly qualified IP optometrists was safe, with stability of disease maintained and few referrals back to HES.

This chapter is written for the welfare of the society, questioning and enlightening the effects of the increment or decrement in the percentage of quality of air causing pollution due to the rise in the traffic post-lockdown due to COVID-19 in metro cities, specifically in Delhi. In this chapter, we address the question about people's preference in moving in the shared taxis to their workplaces or their reluctance and denial of the idea of moving in the shared vehicle because of the fear of getting infected. The sensitivity of the situation will compel the people to move in a single occupied vehicle (SOV). The rise in the number of vehicles on the roads will result in traffic jams and different kinds of pollution where people battling with the pandemic will inevitably get exposed to other health-related issues. We use a BPR (Bureau of Public Roads) model to combat this issue endangering the environment and public health. We exploit the BPR function to relate average travel time to the estimated number of commuters travelling by car. We collect mode share data from the NITI Ayog, the State Resource Centre and other authentic sources, which gives unique figures of the impact of shared mobility in India and how, in its absence, various sectors will get affected. Using the given data and the BPR, we evaluate increased vehicle volumes on the road if different portions of transit and carpool users switch to single-occupancy vehicles and its effect on multiple other factors. Based on the study of densely populated city, Delhi, we predict that cities with significant transit ridership are at risk for extreme traffic and pollution unless transit systems can resume safe with effective protocols.

The Galápagos archipelago is a vast reservoir of terrestrial and marine biodiversity and is particularly susceptible to human, animal, and environmental impacts. Climate change, globalization, and the blurring of human-domestic animal-wildlife interfaces are poised to bring new threats and challenges to the region. A One Health perspective that simultaneously considers human, animal, and environmental health is imperative in assessing and mitigating the challenges facing the Galápagos Islands. Many challenges facing biodiversity in the Galápagos Islands can ultimately be linked to anthropogenic factors. In Part I of this review, we reviewed the impacts of invasive species and identified infectious diseases of importance. In Part II of this review, we discuss the impacts of climate change and ocean acidification, and highlight the effects of several direct human activities, including tourism, overfishing, pollution, land use, and human-wildlife conflict. We also review the socioeconomic and political context of the Galápagos Islands, including current challenges in water and energy use, sanitation, and economic stability. We examine the importance of investment in local development for building resiliency and sustainability in the archipelago. Finally, we discuss the impact of the COVID-19 pandemic in the region. Throughout this two-part review, we build a cohesive picture of One Health in the Galápagos Islands by integrating past work, current needs, and emerging threats. We also consider overarching goals for conservation, ecosystem management, and socioeconomic sustainability that have been previously defined by both governmental and non-governmental stakeholders, and identify discrete, implementable, and interdisciplinary recommendations that will facilitate achievement of those goals.

Cancer is a leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. The progression of cancer is associated with increased cell proliferation, metabolic modifications, resistance to apoptosis, genetic instability, induction of angiogenesis and augmented migratory capability. Recent developments in DNA and RNA analysis have made it possible to study these genetic changes systematically. These advances have enabled us to possess a deeper knowledge of the signaling pathways and involved processes. In-depth studies of the pathways involved in carcinogenesis have led to the identification of pathways that may be targeted for therapeutic purposes. In this review, we provide an overview of the relevant mechanisms and pathways involved in the development and progression of cancer.

Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.

This study presents the development and pilot implementation of an assessment and shared deci-sion-making methodology called the Gezamenlijk Inschatten van Zorgbehoeften (GIZ), designed for youth (health) care professionals working with children and families. The three-phase approach included a needs assessment, development of the GIZ methodology, and pilot implementation in a preventive youth health care and youth care setting, involving parents, adolescents, and youth (health) care professionals. The needs assessment produced nine criteria that the GIZ methodology needed to meet. Based on these criteria, the GIZ methodology was developed and described using the Template for Intervention Description and Replication (TIDieR). The pilot implementation demonstrated high client engagement, satisfaction, and feasibility in daily practice. The GIZ ap-proach promotes appropriate support for families by improving the joint assessment and shared decision-making process in youth (health) care. This study supports the implementation of GIZ in youth (health) care practice and highlights the need for further focus on implementation and sus-tainability.

This study investigates the socio-economic determinants correlated with Post-Traumatic Stress Disorder (PTSD) symptoms amid the 'Guardian of the Walls' operation, in the Israel-Hamas conflict. Our investigation primarily focused on assessing the effects of missile strikes on Israeli civilians. By conducting an in-depth statistical analysis of individual experiences, we sought to unravel the correlation between socioeconomic status and PTSD susceptibility.Our findings reveal a stark disparity in PTSD risks across different socio-economic groups. Individuals from lower socio-economic backgrounds exhibited a notably higher propensity for PTSD symptoms, suggesting that socio-economic adversity intensifies the psychological toll of conflict exposure. Conversely, higher education and stable family environments appeared to mitigate PTSD risks, underscoring the protective role of certain socio-economic factors.The study's implications extend far beyond the immediate context of the Israel-Hamas conflict. By elucidating the heightened vulnerability of lower socio-economic groups to PTSD, it calls for a nuanced approach to mental health intervention in conflict zones. This approach should not only address the direct psychological impact of conflict but also consider the broader socio-economic fabric that shapes individual experiences of trauma.This research contributes to a growing body of knowledge on PTSD in conflict settings, offering valuable insights for policymakers, mental health professionals, and humanitarian organizations. By highlighting the socio-economic dimensions of PTSD, it advocates for more comprehensive, context-sensitive mental health strategies. Such strategies are crucial for addressing the complex array of factors influencing mental health in conflict zones, ultimately paving the way for more resilient and supportive communities.

Choosing new energy vehicles for travel, especially electric vehicles, is an important component of building a low-carbon urban transportation system. However, the charging need of electric vehicle users is still constrained by the unreasonable layout and insufficient supply of public charging piles in the city. Private charging pile sharing as an alternative policy tool can play a very good role in solving this problem. But it needs decision-makers in urban transportation to take corresponding measures to promote. This paper constructs an evolutionary game model to study the decision behavior of participants in private piles sharing platform. Through numerical simulation analysis, it is found that under most parameter conditions, the government tends to establish a shared charging pile platform based on public interests. Private charging pile owners are influenced by the relationship between the cost of supply modification and revenue, and they tend to join the shared platform when they expect to recover the modification cost. The research conclusions of this paper will provide support for exploring how participants make decisions to maximize overall benefits in the development of low-carbon urban transportation.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.

Abstract: Lung cancer, characterized by its heterogeneity, presents a significant challenge in ther-apeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumour’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article ex-plores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. The review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small cell lung cancer and small cell lung cancer, underlining the need for subtype-specific treatments. Key signalling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. The article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. The review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

Urban environments are frequently populated by different insect species. Some of them are very beautiful and appealing to the people around them, such as ladybugs and butterflies, while some others are molestants and even dangerous to public health. Mosquitoes often inhabit urban environments by staying close to their hosts (humans, birds, etc.), while phytophagous species such as stinkbugs find hosts among ornamental plants and shelters during the winter around humans. This article describes the early discoveries and distribution of two invasive mosquito species, Aedes albopictus, and Ae. japonicus (Diptera: Culicidae), which were recorded in Serbia in 2009 and 2018, respectively. Both species are important for human health, due to their nuisance behavior and because they are vectors of many viruses. On the other hand, in 2015 and 2008, two invasive stinkbug species, Halyomorpha halys and Nezara viridula (Hemiptera: Pentatomidae) were observed to spread, respectively. Since then, these species have disrupted human population in urban areas, but also damaged a range of crops and ornamental plants. All species have been monitored in the territory of Serbia, and establishment and distribution have been confirmed so far.

The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6 respectively, are the most abundant expressed connexins in the inner ear. Connexin 43 which is encoded by GJA1 appears to be widely expressed in various organs, including the heart, skin, brain, and inner ear. The mutations that arise in GJB2, GJB6 and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can operate properly. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of connexin 26, the existing controversies in trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness.

During cartilage development, the lineage commitment and condensation of stem cells into chondrocytes and their differentiation involves a ubiquitous signaling cascades and huge numbers of transcriptional factors. The kinetic requirements and the stoichiometry for the expression of key transcriptional factors are relevant and must be met to form proper and functionally competent cartilage tissue. More interestingly also, an exact and precise spatio-temporal distribution of these molecules are as necessary in the proper tissue morphogenesis and patterning as the relevant physical conditions and micro environmental forces playing at the background during embryogenesis. A milestone of experimental achievements has been obtained over the years on several signaling pathways involved in cartilage development. Several fate determining transcriptional factors has also been investigated and determined with regards to the transition of stem cells (pluripotent, embryonic, etc.) into chondrocytes. These transcriptional factors serve as master controllers in chondrocytes proliferation and hypertrophy. Concerns that variability in signaling and transcriptional factors have detrimental effect on cartilage formation and could potentiate most cartilage related diseases have led most scientists to investigate the role of signaling molecules and transcriptional factors implicated in osteoarthritis, rheumatoid arthritis, and other cartilage degenerative diseases. On bases of spatio-temporal distribution of transcriptional factors, there exist functional overlaps, hence, it is difficult to draw a hard line of demarcation of roles at each point of the cell’s life, nonetheless, it is also markedly established that some factors are skewed to the chondrocyte’ survival and proliferation, and others known for their master’s role in the cell’s apoptotic, necrotic and senescence. Here we review some published works on selected signaling pathways and transcriptional factors that are preferentially expressed in chondrogenic cells and their role as major players in cartilage formation, cartilage diseases, along with some highlights of unique signaling molecules that are indispensable in cartilage tissue regeneration and management.

This study investigated the intersecting influence of socioeconomic status and cooking behavior on dietary habits using nationwide Japanese data. The study measured the frequency of balanced meals and breakfast intake as indicators of healthy eating habits and used subjective economic status, subjective spare time, and cooking behavior as the independent variables. It employed multivariate logistic regression analyses to elucidate the relationships among these variables. The results demonstrated that even among economically poor or time-constrained individuals, those preparing meals from ingredients were more likely to eat balanced meals and breakfast than those relying on commercial food or rarely cooking. This finding suggested that cooking behavior can mitigate disparity in healthful eating due to socioeconomic conditions. The study added new insights into the impact of combining socioeconomic status and cooking behavior on dietary habits, which highlights the potential of promoting cooking behaviors, such as teaching cooking skills, as a strategy for reducing socioeconomic dietary disparities.

Cry toxins produced by the bacterium Bacillus thuringiensis are of significant agronomic value worldwide due to their potent and highly specific activity against various insect orders. However, some of these pore-forming toxins display specific activity against a range of human cancer cells whilst possessing no known insecticidal activity, Cry41Aa is one such toxin. Cry41Aa has similarities to its insecticidal counterparts in both its 3-domain toxic core structure and pore-forming abilities, but how it has evolved to target human cells is a mystery. This work shows that some insecticidal Cry toxins can enhance the toxicity of Cry41Aa against hepatocellular carcinoma cells, despite possessing no intrinsic toxicity themselves. This interesting crossover is not limited to human cancer cells, as Cry41Aa was found to inhibit some Aedes-active Cry toxins in mosquito larval assays. Here, we present findings that suggest that Cry41Aa shares a receptor with several insecticidal toxins indicating a stronger evolutionary relationship than their divergent activities might suggest.

Sharing facilities with other households offers the most realistic opportunity for access to sanitation to many households in low-income settings. However, questions remain about the safety of shared toilets, including those shared at the household level. This study sought to compare the usage and microbial safety of household-level shared and unshared toilets in a Ghanaian rural district to investigate any association between their microbial safety and sharing status. A semi-structured questionnaire was used to collect data on the user characteristics of the sampled toilets, while common contact surfaces (door handles and toilet seats) were assessed for faecal contamination following standard swab sampling and analytical protocols. The results of the study indicate that sharing toilets affords about 90% more household-level access to sanitation as compared to single-household toilets. Toilet sharing mostly occurred between two households, with a maximum user population of 14 per toilet. Generally, there was a high prevalence of faecal contamination of the door handles and seats of both shared and unshared toilets, but this had no association with the sharing status of the toilets. The median concentration of E. coli on door handles and seats of shared toilets were 34.3 x 105 and 103.2 x 105 CFU/ml respectively as compared to 54.7 x 105 and 125.0 x 105 CFU/ml respectively on unshared toilets. In conclusion, the sharing of toilets at the household level nearly doubles access to sanitation at home without necessarily exposing the users to a higher risk of faecal-oral disease transmission.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. IL-1β also leads to osteoarthritis through NF-ĸB, IκBζ, and Zn²⁺-ZIP8-MTF1 axis. IL-1, IL-6, and TNFα play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as BMP, FGF, PTHrP, and Indian hedgehog, play roles regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling cause genetic disorders in cartilage and skeletal tissues. FOP, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. mTOR inhibitors were found to prevent ectopic ossification by ACVR1 mutations. ACH and related diseases are autosomal genetic diseases, which manifest severe dwarfism. CNP is currently the most promising therapy for ACH. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels sheds light on the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

There are hundreds, if not thousands, of pathways in a unicellular prokaryotic organism, and all these pathways will have to be controlled, regulated, and coordinated to ensure their proper functioning. As organisms evolve from unicellular eukaryotic organisms to multicellular organisms such as the metazoans, more pathways have evolved to support more diverse biological functions. As a result, fine-tuned control, regulation, and coordination of these pathways becomes an immensely complex and demanding task. Yet, consistent with Darwin’s insight that “nature is prodigal in variety, though niggard in innovation,” nature has produced only a few master coordination hubs for these pathways. Moreover, multicellular organisms such as metazoans have evolved two broader means for coordinating various pathways: cross-talk and communication. Cross-talk operates via having shared components and links between intracellular pathways whereas communication operates via transmitting intercellular signals such as hormones and other ligands with membrane receptors and downstream intracellular signal transductions pathways. Our framework points to a more complex network-based approach for understanding biological pathways and the consequences of their disruption, escape, and malfunction such as cancer, aging, and other diseases.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

One of the leading causes of death worldwide, in both man and woman, is cancer. Despite the significant development in therapeutic strategies, the inevitable emergence of drug resistance limits the success and impedes the curative outcome. Intrinsic and acquired resistance are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis and resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic and epigenetic alterations, the immune system, tumour burden, growth kinetics and undruggable targets. Moreover, transforming growth factor-beta (TGF-β), Notch, epidermal growth factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt)/β-catenin), Janus kinase/signal transducers and activators of transcription (JAK/STAT) and RAS/RAF/mitogen-activated protein kinase (MAPK) signalling pathways are some of the key players that have a pivotal role in drug resistance mechanisms. To guide future cancer treatments and improve results, a deeper comprehension of drug resistance pathways is necessary. This review will cover both intrinsic and acquired resistance and give a comprehensive overview of recent research on mechanisms that enable cancer cells to bypass barriers put by treatments, and like “satellite navigation”, find alternative routes to carry on their “journey” to cancer progression.

Driven by the proliferation of DC energy sources and DC end-use devices (e.g., photovoltaics, battery storage, solid-state lighting, and consumer electronics), DC power distribution in buildings has recently emerged as a path to improved efficiency, resilience, and cost savings in the transitioning building sector. Despite these important benefits, there are several technological and market barriers impeding the development of DC distribution, which have kept this technology at the demonstration phase. This paper identifies specific end-use cases for which DC distribution in buildings is viable today. We evaluate their technology and market readiness, as well as their efficiency, cost, and resiliency benefits while addressing implementation barriers. The paper starts with a technology review, followed by a comprehensive market assessment, in which we analyze DC distribution field deployments and their end-use characteristics. We also conduct a survey of DC power and building professionals through on-site visits and phone interviews and summarize lessons learned and recommendations. In addition, the paper includes a novel efficiency analysis, in which we quantify energy savings from DC distribution for different end-use categories. Based on our findings, we present specific adoption pathways for DC in buildings that can be implemented today, and for each pathway we identify challenges and offer recommendations for the research and building community.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

Subseasonal-to-seasonal (S2S) weather forecasting has improved in recent years, thanks partly to better representation of physical variables in models. For instance, realistic initializations of snow and soil moisture in models yield enhanced predictability on S2S time scales. Snow depth and soil moisture also mediate month-to-month persistence of near-surface air temperature. Here the role of snow depth as predictor of temperature one month ahead in the Northern Hemisphere is probed via two causal pathways. Through the first pathway, snow depth anomalies in month 1 cause snow depth anomalies in month 2, which then cause temperature anomalies in month 2. This pathway represents the snow–albedo feedback, as well as cooling due to insulation, emissivity and heat loss. It is active from fall to summer, and its effect peaks in March/April in the midlatitudes and in May/June at high latitudes. A complementary second pathway, where snow depth anomalies in month 1 cause soil moisture anomalies in month 2, which then cause temperature anomalies in month 2 through soil moisture–temperature feedbacks, is only active in spring and summer. Its effect peaks later in the warm season than the effect of the first pathway. Geographically, snow depth mediates north of, and soil moisture south of, the areas with the highest temperature predictability from snow depth. These results indicate that the two pathways describe complementary physical mechanisms. The first pathway embodies month-to-month persistence of snow depth, and the second pathway represents melting of snow from one month to the next.

Building fires are preventable incidents that have proven to be both deadly and costly. Addressing their root causes will lead to safer neighbourhoods for families and businesses to live and operate in. Multiple studies have established the effect of residents’ socioeconomic compositions on an area’s building fire rates; however, the existing model based on the classical stepwise regression procedure has several limitations. This paper aims to construct a more accurate predictive model of building fire rates based on a set of explanatory socioeconomic variables. In building the socioeconomic model, a backward elimination by Robust Final Predictor Error (RFPE) criterion is proposed to enhance the forecasting capability of the model. The proposed method has been implemented on the census data and the fire incident data of the South East Queensland region in Australia. A cross-validation was then conducted to assess the model’s accuracy. In addition, comparative analyses of other elimination criteria, such as p-value, adjusted R-squared, Akaike’s Information Criterion (AIC), Bayesian Information Criterion (BIC) and predicted residual error sum of squared (PRESS), were conducted. The cross-validation analyses demonstrate that the proposed criterion is a more accurate predictive model based on a couple of goodness-of-fit measures. All in all, the RFPE equation was found to be a suitable criterion for the backward elimination procedure in the socioeconomic modelling of building fires.