Purpose: Emotional voice conveys important social cues that demand listeners’ attention and timely processing. This event-related potential study investigated the feasibility of a multi-feature oddball paradigm to examine adult listeners’ neural responses to detecting emotional prosody changes in non-repeating naturally spoken words. Method: Thirty-three adult listeners completed the experiment by passively listening to the words in neutral and three alternating emotions while watching a silent movie. Previous research documented pre-attentive change-detection electrophysiological responses (e.g., MMN, P3a) to emotions carried by fixed syllables or words. Given that the MMN and P3a have also been shown to reflect extraction of abstract regularities over repetitive acoustic patterns, the current study employed a multi-feature oddball paradigm to compare listeners’ MMN and P3a to emotional prosody change from neutral to angry, happy, and sad emotions delivered with hundreds of non-repeating words in a single recording session. Results: Both MMN and P3a were successfully elicited by the emotional prosodic change over the varying linguistic context. Angry prosody elicited the strongest MMN compared to happy and sad prosodies. Happy prosody elicited the strongest P3a in the centro-frontal electrodes, and angry prosody elicited the smallest P3a. Conclusions: The results demonstrated that listeners were able to extract the acoustic patterns for each emotional prosody category over constantly changing spoken words. The findings confirm the feasibility of the multi-feature oddball paradigm in investigating emotional speech processing beyond simple acoustic change detection, which may potentially be applied to pediatric and clinical populations.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

Our previous research provides evidence that vergence eye movements may significantly influence cognitive processing and could serve as a reliable measure of cognitive issues. The rise of consumer-grade eye tracking technology, which uses sophisticated imaging techniques in the visible light spectrum to determine gaze position, is noteworthy. In our study, we explored the feasibility of using webcam-based eye tracking to monitor the vergence eye movements of patients with Mild Cognitive Impairment (MCI) during a visual oddball paradigm. We simultaneously recorded eye positions using a remote infrared-based pupil eye tracker. Both tracking methods demonstrated more pronounced cognitive vergence responses for targets as opposed to distractors. In summary, the use of a consumer-grade webcam to record cognitive vergence shows potential. This method could potentially lay the groundwork for future research aimed at creating an affordable screening tool for mental health care.

In the realm of metal steel and iron manufacturing, there is a constant drive to optimize production efficiency and enhance the quality of the final products. This abstract explores a paradigm shift in this industry through the utilization of Computational Fluid Dynamics (CFD) as a powerful tool for achieving these goals .The study focuses on various critical aspects of the manufacturing process. Firstly, it delves into three-phase processes such as slag and gas entrainment in liquid steel, which have a significant impact on the overall product quality. Understanding and optimizing these processes is crucial to ensure the desired chemical composition and physical properties of the final metal.The abstract investigates the role of CFD in vacuum degassing, a process that plays a pivotal role in removing impurities, such as hydrogen and oxygen, from the liquid steel. By leveraging CFD to simulate and analyze the fluid flow patterns, researchers and engineers can design more efficient vacuum degassing systems, leading to improved product purity and reduced waste.Another crucial aspect explored in this abstract is the alloy melt and mixing process. By employing CFD simulations, researchers can gain insights into the movement of different alloy components and optimize their distribution within the melt. This aids in achieving the desired alloy composition, ensuring uniformity, and enhancing the mechanical properties of the final product.In addition, the study delves into the movement and flotation of inclusions, which are unwanted impurities present in the metal. CFD can be utilized to model and analyze the behavior of these inclusions, enabling engineers to design efficient strategies for their removal, thereby enhancing the purity and integrity of the final product.Moreover, the abstract considers the impact of melt temperature losses, which can occur during different stages of the manufacturing process. By employing CFD, it becomes possible to understand and mitigate these temperature losses, leading to improved energy efficiency and better control over the manufacturing parameters.Part 1 of this abstract critically evaluates the use of CFD in iron making, analyzing its benefits and limitations. It highlights how CFD can aid in process optimization, improving the understanding of complex phenomena involved in iron making, and ultimately leading to enhanced production efficiency.Part 2 focuses on the application of CFD in steel making and steel operation. It explores the fluid flow dynamics during different stages of steel production, including refining, casting, and rolling. By leveraging CFD, engineers can optimize these processes, leading to improved product quality, reduced defects, and increased productivity.This abstract demonstrates the transformative potential of Computational Fluid Dynamics in metal, steel, and iron manufacturing. By utilizing CFD as a tool to model and analyze complex fluid flow phenomena, researchers and engineers can revolutionize the production process, maximizing efficiency, and ensuring high-quality end products.

Good governance in natural resource management (NRM) is one of the most challenging issues in developing countries that often inappropriately embedded in national policies and political agendas. It is, in fact, even more important for countries like Bangladesh with exceptionally high pressure and dependence on its natural resources for sustaining rural livelihoods. Globally, nowadays, good governance is considered as one of the key factor for achieving the goal of sustainable development and biodiversity conservation. Bangladesh, of late has responded to that global zeal by involving local communities in the management of country’s declining forest and other natural resources. The colonial legacy of the forestry sector of Bangladesh was planned and, managed as interim projects through donors’ prescriptions. Thus, institutions, management processes and conservation outcomes were problematic. The conventional approach adopted by colonial and post-colonial regimes for forest management also proved to be inefficient due to its top-down management system. The absolute dependency on donor support, and their prescription sometimes worsened the situation both ecologically and socially. Global, regional and local trends supported the need for a different dimension in the governance paradigms. The introduction of a pluralistic approach, known as co-management in protected areas (PAs) is an example of an attempt whereby shared governance mechanism are implemented to attain the desired goals of conservation that will also address the livelihoods and aspirations of communities living in and around PAs of the country. However, in designing future forest and PA regimes the concern of the external aid support and attached conditions remain a reality that needs to be addressed. Adequate attention should be given to our vanishing biodiversity, culture and community livelihoods through devising an appropriate governance mechanism recognizing and supporting local rights, access and participation in the environmental management. It is now time to mainstream the adhoc nature of governance according to our national conservation strategy and policy frameworks in order to achieve the goals and objectives of the Bangladesh NRM sector addressing the human and community right of people in the specific context of forest protected areas management.

The conceptual and theoretical backbones of symmetry/asymmetry detections or similarity/dissimilarity, and identity/unidentity study are automorphism or isomorphism respectively. However, the development of equations and methods for symmetry/asymmetry detections, similarity/dissimilarity, and identity/unidentity measures deviates from these backbones. In this article, an equation was proposed for symmetry/asymmetry detections, similarity/dissimilarity, and identity/unidentity measures, and proved that its isoreflective pairs-points are functionally bijective and inverse. The proposal, called Kabirian-based optinalysis, is based on the conceptual and theoretical frameworks of automorphism and isomorphism. The Kabirian-based optinalysis is also proven and characterized as invariant (robust) under translation (i.e., scaling and location shift), and rotation or reflection. Computing codes were written in python language for Kabirian-based optinalysis to serve as working codes for application and verification.

Nutrigenetics concerns individual differences in the reaction to food based on the genetic factors. Nutrigenomics analyses direct influences of nutrients on gene expression. Both terms are explained in our review article. Nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and of new ‘omic’ technologies. It is often difficult to appreciate their relevance in the practice of preventive approaches for optimizing health, delaying onset of disease and diminishing its severity. This paper represents a review about the current research on Nutrigenomics and Nutrigenetics, and provide scientific data for a new integrated clinical approach.

Scientific, technical and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure and other product- and process-related attributes are comparable within the limits of testing then a biosimilar candidate would have safe safety and efficacy as its reference products. The current model of animal and human testing becomes redundant since all of these studies have much lower sensitivity and reproducibility in confirming biosimilarity. The recent AI-based protein structure prediction model has confirmed that the 3D structure can be predicted from the amino acid sequence, reducing the need for structural analysis; however, the new test methods based on MS are millions of times more sensitive and accurate. While the regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, removing clinical pharmacology profiling brings a dramatic paradigm shift, reducing development costs without compromising safety and efficacy. Also shared is a list of 160+ products ready to enter as biosimilars. Major actions from regulatory agencies and developers are required to make this paradigm shift.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Consciousness is usually interpreted as a state of being aware of one’s environment as well as self, while awareness is understood as knowledge of something. Despite their semantic differences, in philosophy, these terms are often used interchangeably, as is the case of the hard problem of consciousness proposed by Chalmers, which in fact is the hard problem of awareness. Trilogy paradigm of consciousness (or simply “trilogy”) offers a new paradigm where consciousness is the result of a unique interaction between awareness and the decision-making process. By conferring the input of awareness to the decision-making process, a new mental function of awareness-based choice selection (ABCS) or true free will emerges. Likewise, application of the power of decision-making to the process of awareness gives rise to discretionary selection of information for awareness (DSIA) or intentional attention. The intertwined actions of ABCS and DSIA comprise “I” which is the faculty of our consciousness and is what sets natural intelligence (NI) apart from artificial intelligence (AI). Based on trilogy, mind is an unconscious compilation of all mental function excluding ABCS and DSIA that are the essence of consciousness. As humans, we are a union of “I,” our minds, and our bodies.

We present a summary of the main results within the Scale Invariant Vacuum (SIV) paradigm as related to the Weyl Integrable Geometry. After a brief review of the mathematical framework, we will highlight the main results related to inflation within the SIV [9], the growth of the density fluctuations [8], and the application of the SIV to scale-invariant dynamics of Galaxies, MOND, Dark Matter, and the Dwarf Spheroidals [7]. The connection of the weak-field SIV results to the un-proper time parametrization within the reparametrization paradigm is also discussed [14].

As noted in the introductory quotation, an ideal map was long ago seen as the map of the map, the map of the map, of the map, and so on endlessly. This recursive perspective on maps, however, has received little attention in cartography. Cartography, as a scientific discipline, is essentially founded on Euclidean geometry and Gaussian statistics, which deal with respectively regular shapes, and more or less similar things. It is commonly accepted that geographic features – such as rivers, cities, streets and building – are not regular and that the Earth’s surface is full of fractal or scaling or living phenomena with far more small things than large ones at different levels of scale. This paper argues for a new paradigm in mapping, based on fractal or living geometry and Paretian statistics, and – more critically – on the new conception of space, conceived and developed by Christopher Alexander, that space is neither lifeless nor neutral, but a living structure capable of being more living or less living. The fractal geometry is not limited to Benoit Mandelbrot’s framework, but is extended towards Christopher Alexander’s living geometry and based upon the third definition of fractal: A set or pattern is fractal if the scaling of far more small things than large ones recurs multiple times. Paretian statistics deals with far more small things than large ones, so it differs fundamentally from Gaussian statistics, which deals with more or less similar things. Under the new paradigm, I make several claims about maps and mapping: (1) Topology of geometrically coherent things – in addition to that of geometric primitives – enables us to see a scaling or fractal or living structure; (2) Under the third definition, all geographic features are fractal or living, given the right perspective and scope; (3) Exactitude is not truth – to paraphrase Henri Matisse – but the living structure is; and (4) Töpfer’s law is not universal, but scaling law is. All these assertions are supported by evidence, drawn from a series of previous studies. This paper demands a monumental shift in perspective and thinking from what we are used to on the legacy of cartography and GIS.

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiome. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiome on PD and whether this may be a new paradigm for treating this devastating disease.

Human-generated, natural occurrences and other actions connected with the petroleum industry have contributed expansively to the contamination of numerous areas of human habitant, thus effecting overwhelming challenges and constraints to sustainable human health, development and the biosphere. The sites commonly associated include derelict pits, hydrocarbon onshore release sites, and places to where oil slicks exuding from offshore releases are blown onshore. In diverse cases, remediation is pertinent to restore the affected ambient. This is required despite the complexity and intricate pore structure and fluid trafficking trajectories of soil which are not easily amenable to remediation. Due to the complex assemblage of contaminated soil, it is necessary to conduct an encompassing site assessment by considering the potential impact of the environment and human health prior to proper selecting and implementing of a desirable remediation process. There are extant remediation methodologies which are effective and efficient for the clean up of contaminated shorelines and other petroleum-contaminated sites involving inter alia agricultural activities. There are salient variations in the techniques to expunge contaminants regarding spatiotemporal and pecuniary costs or considerations due to the gross environmental hazards entailed. This study provides for the opportunity to harness and sustain the capacity for the mitigation of untoward impacts, and induce the latitude for an enabling condition in sustainable human health, environment and development in the petroleum industry and other anthropogenic activities.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

Classically the walk in biped robotics was obtained controlling balance during the whole step, i.e. guaranteeing that the pressure point under the soles always stayed in the polygon of the supporting feet. However, this assumed that the feet were able to transfer torque to the ground during the whole gait cycle. In spite of the fact that the amount of transferrable torque in the feet-ground contact is limited, it is possible only during some phases of the step, and the overall process is energetically inefficient. On the other side, starting from the passive motion of the rimless wheel falling on an inclined surface, and ending to the inverted pendulum with a compass, balance in the whole was proven in spite of dynamical instability inside each step. Along this line results of Foot Placement Estimation (FPE) in 2-D and 3-D showed how energy efficient walk was possible, emulating the human walk with a free fall on the swing foot and energy restitution at the foot collision with the ground for the next step. This model assumes pointy feet, so without torque transfer to the ground. In the realm of FPE, in previous papers the present author adopted the 3-D inverted pendulum in polar coordinates (Spherical Inverted Pendulum - SIP) to introduce omnidirectional walks with arbitrarily changing characteristics. No torque control was used during the step, i.e the pendulum was always in free fall at each step, the only control actions were at the beginning of the next step. These actions are: the change of angular velocities at the start of a new step, with respect to those given after the collision (emulating the torque action in the brief double stance period), to recover for the losses, and the preparation of the position in the frontal and sagittal planes of the swing foot for the next collision. The present paper improves this paradigm, proposing a general model to account for all characteristics of the biped and of the gait, with adding a minimum of dynamical complexity with respect to the SIP. This model allows, not only to walk omnidirectionally on a flat surface, but also to go up and down staircases.

Reading is a complex cognitive task involving processes from different systems. The present work aims to identify some points of divergence reported in the reading literature and discuss them in a new experimental paradigm framework. Inspired by the paradigms of perceptual identification and rapid parallel presentation (RPVP), we emphasize that the originality of our experimental paradigm lies in the recruitment of multi-stable Arabic percepts within the region where low-level processing occurs (i.e., the visual span area). With good flexibility, the current paradigm has reached higher-order processing levels. In agreement with previous works highlighting the parafoveal-on-foveal effect, results suggest parallel word processing. Furthermore, they suggest a rapid extraction of syntactic and semantic information from words in sentences while attributing an advantage to semantic processing in the emergence of the sentence superiority effect.

Since 1974, when Heinz von Foerster made the distinction between “the cybernetics of observed systems” as first-order cybernetics (1oC) and “the cybernetics of observing systems” as second-order cybernetics (2oC), cybernetics has been dominated by this observer-centric paradigm that he claimed cannot be extended meaningfully to a third-order. Rather than attempting to extend his paradigm, we derive an alternative, model-centric paradigm from first principles of regulation that naturally extends to three orders, where the third order is ethical regulation. We thus consider a type of regulator that requires a third model and a third observer: If the third model is a model of acceptable (ethical) situations, then a third observer is a necessary element of the system’s “conscience” that prevents or detects any violations of the model of ethical situations. In this paradigm, the cybernetics of systems that are designed to exhibit ethical behaviour can be characterized as third-order cybernetics (3oC). By being able to extend the paradigm to include ethical systems, the model-centric paradigm brings clarity and utility that is not possible using the philosopher-friendly observer-centric paradigm and its under-specified (abstract) observers. Finally new definitions for cybernetics are proposed that clearly differentiate between the science and the philosophy, of cybernetics.

We humans are natural-born engineers. As such, we model after machines not only isolated, naturally occurring systems, but also the basic laws of physics, sharing with machines a local-evolution-of-state `grammar'. However, previous work by the author casts doubt upon this mechanistic paradigm, suggesting that it is to blame for the stubbornness of many open problems in physics. Simple experiments are therefore proposed to identify `non-machines'. In one experiment, `non mechanistic correlations' in the spirit of Bell are sought in a pair of separated but previously coupled (macroscopic) chaotic systems. In another it is tested whether chaotic systems could fuzzily `remember their future' in the sense that a future binary perturbation applied to them could be inferred from their present behavior with probability>1/2. Chaotic systems are chosen as candidates because the long-time application of their (deterministic) mechanistic description is conceptually groundless: All scales are significant and mutually coupled in that regime, down to scales governed by QM, yet the quantum-classical transition remains inexplicable---if only due to the measurement problem. Similarly for non-deterministic chaotic systems, modeled as such purely for defying a short-time deterministic mechanistic description. Should a non mechanistic signature be found in such simple systems, the implications for science as a whole and life sciences in particular cannot be overstated.

Fossils constitute the principal repository of data that allow for independent tests of hypotheses of biological evolution derived from observations of the extant biota. Traditionally, transformational series of structure, consisting of sequences of fossils of the same lineage through time, have been employed to reconstruct and interpret morphological evolution. More recently, a move toward an updated paradigm was fueled by the deliberate integration of developmental thinking in the inclusion of fossils in reconstruction of morphological evolution. The vehicle for this is provided by structural fingerprints – recognizable morphological and anatomical structures generated by (and reflective of) the deployment of specific genes and regulatory pathways during development. Furthermore, because the regulation of plant development is both modular and hierarchical in nature, combining structural fingerprints recognized in the fossil record with our understanding of the developmental regulation of those structures produces a powerful tool for understanding plant evolution. This is particularly true when the systematic distribution of specific developmental regulatory mechanisms and modules is viewed within an evolutionary (paleo-evo-devo) framework. Here, we discuss several advances in understanding the processes and patterns of evolution, achieved by tracking structural fingerprints with their underlying regulatory modules across lineages, living and fossil: the role of polar auxin regulation in the cellular patterning of secondary xylem and the parallel evolution of arborescence in lycophytes and seed plants; the morphology and life history of early polysporangiophytes and tracheophytes; the role of modularity in the parallel evolution of leaves in euphyllophytes; leaf meristematic activity and the parallel evolution of venation patterns among euphyllophytes; mosaic deployment of regulatory modules and the diverse modes of secondary growth of euphyllophytes; modularity and hierarchy in developmental regulation and the evolution of equisetophyte reproductive morphology. More generally, inclusion of plant fossils in the evo-devo paradigm has informed discussions on the evolution of growth patterns and growth responses, sporophyte body plans and their homology, sequences of character evolution, and the evolution of reproductive systems.

Wicked problems, such as climate change, systemic poverty, and healthcare inequalities, rep- resent the most pressing and intractable challenges facing society today. We propose a novel approach that leverages complex systems theory as a comprehensive framework for understanding and tackling these challenges. By applying concepts such as state space analysis, attractors, and nonlinear dynamics, we offer a sophisticated toolkit for mapping the intricate web of interactions defining wicked problems and exploring potential interventions. Our approach moves beyond tradi- tional reductionist methods, embracing the inherent complexity and dynamism of these issues. We demonstrate how this framework can lead to more nuanced, adaptive, and effective strategies for addressing persistent societal problems. Despite the prevalence of wicked problems and the avail- ability of complex systems theory, practical applications of this approach remain uncommon. This paper aims to bridge this gap, illustrating the potential of complex systems theory to transform our engagement with intractable problems and pave the way for more robust, holistic solutions. By synthesizing insights from mathematics, physics, and social sciences, we present a transdisci- plinary approach that promises to revolutionize how we conceptualize and address society’s most challenging issues.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

Specialized, reductionist, and linear approaches are applied in clinical research; they are based on linear logic and used towards therapeutic molecule-based targets. However, those approaches do not consider a systemic vision that describes the remote cause of the pathogenic activation. We propose new theoretical and practical methods for the next drug generation development. Self-organization, network structure, hierarchical organization, non-linearity, feedback circuits, reactions to information, and the view of drugs as information clarify the existing pharmacological methods. We suggest a perspective and hierarchical vision of the human organism based on six levels (mechanic and structural; metabolic; bodily dynamic; emotional, cognitive, spiritual). The therapy should restore the self-organization of every level using the “intelligent” modulation of the network responses. Multi-targeted drugs should act on the remote cause of the pathogenic cascade and be administered based on personal variability and networks. This approach may help the development of individualized, precise, and integrated medicine.

We present a summary of the main results within the Scale Invariant Vacuum (SIV) paradigm based on the Weyl Integrable Geometry (WIG) as an extension to the standard Einstein General Relativity (EGR). After a brief review of the mathematical framework, where we also highlight the connection between the weak-field SIV equations and the notion of un-proper time parametrization within the reparametrization paradigm, we continue with the main results related to early Universe; that is, applications to inflation, Big Bang Nucleosynthesis, and the growth of the density fluctuations within the SIV. In the late time Universe the applications of the SIV paradigm are related to scale-invariant dynamics of galaxies, MOND, dark matter, and the dwarf spheroidals where one can find MOND to be a peculiar case of the SIV theory. Finally, within the recent time epoch, we highlight that some of the change in the length-of-the-day (LOD), about 0.92 cm/yr, can be accounted for by SIV effects in the Earth-Moon system.

This conceptual article is aimed at evaluating the COVID19 impacts on the global economy and to postulating an ‘economic paradigm shift’. We argue that the existing economic, political, and trade principles have been challenged due to the global pandemic issue. We also compare the COVID19 impact on Western countries and Eastern countries with their control mechanisms. The emerging of new economies is due to the travel restrictions and disrupt of the global economies are discussed that pave a gateway to the economic paradigm shift. The article finally assesses the advent of 5G technology and its implications to face any future health threats that will lead to the next economic paradigm shift in the modern world.

The ubiquitous problem of electrical energy waste is driven by human error, in which people regularly forget to turn off appliances when they leave a room, resulting in excessive consumption. The paper presents an energy-efficient TRIZ-inspired (EETRIZ) paradigm to automate consumer electronic devices in order to address this problem. Employing motion detection at entry and exit points, the system discerns room occupancy, effectively managing electrical appliances like lamps, fans, and air conditioners. The integration of theory of inventive problem solving (TRIZ) principles guides the ideation and design of an efficient switching mechanism. The system demonstrates that it is flexible by controlling multiple electronic consumer devices simultaneously. This paradigm can be used in a variety of environments, such as homes, offices, schools, and universities, and its goal is to reduce excessive energy use that results from human negligence. With an emphasis on economic viability and environmental impact, the proposed EETRIZ paradigm not only offers enhanced energy efficiency but also lays the groundwork for long-term sustainability practices, aligning with global efforts towards greener and smarter energy management. The proposed EETRIZ is implemented on C platform with support of MPLAB, Nuvoton 8051 Serie MCU Programming, GMPLibrary (GMP-5.1.1) and, Miracl Library. The proposed EETRIZ outperforms current state-of-the-art methods in terms of energy efficiency, cost-effectiveness, precision, and user-friendliness, according to hardware testing.

The reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an established tool for the diagnosis of RNA pathogens. Its potential for automation has caused it to be used as a presence/absence diagnostic tool even when RNA quantification is not required. This technology has been pushed to the forefront of public awareness by the COVID-19 pandemic, as its global application has enabled rapid and analytically sensitive mass testing, with the first test targeting three viral genes published within days of the publication of the SARS-CoV-2 genomic sequence. One of those, targeting the RNA-dependent RNA polymerase gene, has been heavily criticised for supposed scientific flaws at the molecular and methodological level and this criticism has been extrapolated to doubts about the validity of RT-qPCR for COVID-19 testing in general. We have analysed this assay in detail and our findings reveal some limitations, but also highlight the robustness of the RT-qPCR methodology for SARS-CoV-2 detection. Whilst our data show that some errors can be tolerated, it is always prudent to confirm that primer and probe sequences complement their intended target, since when errors do occur, they may result in a reduction in the analytical sensitivity. However, in this case it is unlikely that a mismatch will result in poor specificity or significant number of false positive SARS-CoV-2 diagnoses, especially as this is routinely checked by diagnostic laboratories as part of their quality assurance.

The pandemic caused by SARS-CoV-2 virus obstructed the Chinese economy and has expanded to the rest of the world at a rapid pace affecting at least 215 countries, areas and territories. The advancement of the disease and its economic repercussions is profoundly ambiguous, making it challenging for policymakers to formulate suitable microeconomic and macroeconomic policy responses. The scenarios in this paper illustrate how an outbreak could significantly affect the global economy in the short run. It has been estimated that each additional month of crisis would cost from about 2.5-3% of the global GDP and that the GDP growth would take a blow, reaching about 3-6%, depending on the country. Scenarios also suggest that GDP can drop by more than 10% and even exceed 15% in some countries. Via addressing the economic consequence of COVID-19 in different industries and countries, the paper presents assessments of the likely global economic costs of COVID-19 and the GDP growth of different countries. Economies will be negatively affected because of the high number of jobs at risk. Countries highly dependent on foreign trade are more negatively affected. Given that disease and its economic influence are highly unpredictable in numerous aspects, the global economy at the moment is the most critically threatened in history.

Crowdsourcing is one of the new themes that has appeared in the last decade. Considering its potential, more and more organisations reach for it. It is perceived as an innovative method that can be used for problem solving, improving business processes, creating open innovations, building a competitive advantage, and increasing transparency and openness of the organisation. Crowdsourcing is also conceptualised as a source of a knowledge-based organisation. The importance of crowdsourcing for organisational learning is seen as one of the key themes in the latest literature in the field of crowdsourcing. Since 2008, there has been an increase in the interest of public organisations in crowdsourcing and including it in their activities. This article is a response to the recommendations in the subject literature, which states that crowdsourcing in public organisations is a new and exciting research area. The aim of the article is to present a new paradigm that combines crowdsourcing levels with the levels of learning. The research methodology is based on an analysis of the subject literature and exemplifications of organisations which introduce crowdsourcing. This article presents a cross-sectional study of four Polish municipal offices that use four types of crowdsourcing, according to the division by J. Howe: collective intelligence, crowd creation, crowd voting, and crowdfunding. Semi-structured interviews were conducted with the management personnel of those municipal offices. The research results show that knowledge acquired from the virtual communities allows the public organisation to anticipate changes, expectations, and needs of citizens and to adapt to them. It can therefore be considered that crowdsourcing is a new and rapidly developing organisational learning paradigm.

Ultraviolet imaging has been applied in volcanology over the last ten years or so. This provides considerably higher temporal and spatial resolution volcanic gas emission rate data than available previously, enabling the volcanology community to investigate a range of far faster plume degassing processes, than achievable hitherto. To date this has covered rapid oscillations in passive degassing through conduits and lava lakes, as well as puffing and explosions, facilitating exciting connections to be made for the first time between previously rather separate sub disciplines of volcanology. Firstly, there has been corroboration between geophysical and degassing datasets at ≈ 1 Hz expediting more holistic investigations of volcanic source-process behaviour. Secondly, there has been the combination of surface observations of gas release, with fluid dynamic models (numerical, mathematical and laboratory) for gas flow in conduits, in attempts to link subterranean driving flow processes to surface activity types. There has also been considerable research and development concerning the technique itself, covering error analysis and most recently adaptation of smartphone sensors for this application, to deliver gas fluxes at a significantly lower instrumental price point than possible previously. At this decadal juncture in the application of UV imaging in volcanology, this article provides an overview of what has been achieved to date as well as a forward look to potential future research directions, in particular covering the first use of UV cameras to generate volcanic gas composition ratio imagery.

In this work, an IoT system with edge computing capability is proposed facilitating postoperative surveillance of patients who have undergone knee surgery. The main objective is to reliably identify whether a set of orthopedic rehabilitation exercises are executed correctly, which is critical since, it is often necessary to supervise patients during the rehabilitation period so as to avoid injuries or long recovery periods. The proposed system leverages Internet of Things (IoT) paradigm, in combination with Deep Learning and Edge Computing to classify the extend-flex movement of one’s knee via embedded Machine Learning (ML) classification algorithms. The contribution of the proposed work is multilayered. Furthermore as an outcome of this work a dataset of labeled knee movements is freely available on https://www.kaggle.com/datasets/billskarm/knee-range-of-motion to the research community. It also provides real time movement detection with an accuracy reaching 100%, which is achieved with a ML model trained to fit a low cost, off the shelf, Bluetooth Low Energy platform. The proposed Edge Computing approach allows predictions to be performed on-device rather than solely relying on a cloud service. This yields critical benefits in terms of wireless bandwidth and power conservation, drastically enhancing device autonomy, while delivering reduced event detection latency. In particular, the “on device” implementation is able to yield a drastic 99,9% wireless data transfer reduction, a critical 39% prediction delay reduction and a valuable 17% increase of prediction event. Finally, enhanced privacy comprises another significant benefit from the implemented Edge Computing ML model as sensitive data can be processed on-site and only events or predictions are shared with the medical personnel.

The overarching purpose of this review was to highlight the utility of different aerobic field tests in terms of the parameters they provide, with a specific focus on shuttle running and all-out testing. Various field tests are discussed in detail and are categorised according to linear continuous running tests (e.g. 12-minute Cooper Test, University of Montreal Track Test [UMTT], 1200/1600 m time trials, 3-minute all-out test for running [3MT]), intermittent shuttle running tests (e.g. yo-yo inter-mittent recovery test level 1 [YYIR1], 30-15 intermittent fitness test [IFT], and the intermittent all-out shuttle test [IAOST]), and continuous shuttle running tests (e.g. 1.2 km shuttle run test [1.2SRT], maximal multi-stage 20-m shuttle test [MSR], 25-m, 30 m and 50-m 3-minute all-out shuttle test [AOST]). Readers will be guided through the theoretical and practical underpinnings of the 3MT methodology, where the all-out testing methodology is stationed within the testing paradigm, and how to practically implement and interpret the results thereof.

The Hyper-Torus Universe Model (HTUM) proposes a novel framework to unify quantum mechanics, cosmology, and consciousness. This paper introduces HTUM's core concept: a higher-dimensional hyper-torus encompassing all possible states of existence. HTUM suggests that the universe functions as a quantum system where all outcomes are inherently connected, with consciousness playing a significant role in actualizing reality. The model introduces several key innovations, including the universe's 4-dimensional toroidal structure (4DTS), providing a new geometric interpretation of spacetime. HTUM presents dark matter and dark energy as nonlinear probabilistic phenomena within this toroidal framework, offering a unique perspective on their nature and interactions. The model proposes a mechanism for wave function collapse through universal self-observation, bridging quantum mechanics and gravity. It introduces a Topological Vacuum Energy Modulator (TVEM) function, offering a potential resolution to the cosmological constant problem. Furthermore, HTUM integrates consciousness as a fundamental aspect of the universe, influencing quantum state actualization and potentially resolving the hard problem of consciousness. The model explores the implications of a timeless singularity and the emergence of time as a product of causal relationships within the toroidal structure. This framework addresses critical challenges in modern physics, including the nature of quantum entanglement, the origin and fate of the universe, and the relationship between mind and matter. The paper discusses the mathematical formulation of HTUM, its implications for quantum mechanics and cosmology, and its potential to bridge the gap between science and philosophy. We present detailed predictions for the cosmic microwave background (CMB) power spectrum, gravitational wave signatures, and large-scale structure formation, demonstrating how HTUM differs from the standard ΛCDM model. Our analysis reveals distinctive oscillatory patterns in the relative difference between HTUM and ΛCDM predictions, with deviations reaching up to ±20% at certain scales. The paper also explores the unification of fundamental forces within the HTUM framework, proposing novel approaches to particle physics and quantum field theory. It introduces the concept of unified mathematical operations, suggesting a more holistic approach to mathematical thinking that aligns with the model's interconnected view of the universe. Additional testable predictions and proposed experimental approaches are discussed, including advanced space-based tests and laboratory experiments probing quantum gravity effects. These specific, quantifiable predictions offer multiple avenues for empirical validation, highlighting HTUM's potential to be distinguished from ΛCDM and other alternative cosmological models. HTUM represents a significant new perspective in our understanding of the universe, inviting further research and exploration into the nature of reality, consciousness, and the fundamental structure of the cosmos. By providing a comprehensive framework that unifies various aspects of physics, cosmology, and consciousness studies, HTUM offers a promising path toward a more complete understanding of our universe.

This article introduces existential wellbeing (EWB) as one of the most ignored but also the most important kind of wellbeing, especially for people who experience life-limiting diseases and need palliative care (Wong & Yu, 2021). This article will not only review the literature regarding the nature and practice of existential wellbeing in palliative care, but also propose a preliminary Existential Wellbeing Scale. EWB is defined as the quality-of-life characterized by living well and dying well in spite of pain, obstacles, and the shadow of death; wellbeing within the context of human suffering can only be fully understood from the perspective of existential positive psychology (EPP), dedicated to the study of sustainable wellbeing based on the foundation of transcending suffering. The basic tenets of EPP are (1) redefining positivity or wellbeing in terms of seeing and being the light in the darkness; (2) focusing on the dialectical process of navigating an adaptive balance; and (3) re-orienting one’s life attitude from egotism to self-transcendence (Wong, 2023a). More specifically, EWB depends on some combination of the following experiences: (1) Prior experience of overcoming adversity; (2) Existential intelligence (Gardner, 2020) in addressing existential concerns; (3) Existential wisdom of the soul (Wong 2022a; Wong, Ho, et al, 2023a) to achieve existential wellbeing and sustainable flourishing; (4) Spiritual wellbeing based on spiritual values such as faith, hope, and love (Wong, 2023); (5) Knowledge of meaning-focused coping (Eisenbeck et al., 2021); and (6) The new paradigm of self-transcendence (Reed & Haugan, 2021; Wong, Arslan et al., 2021; Wong, Ho et al., 2023b) to transcend and transform suffering into wellbeing and triumph.

An integration between the principles in supply change management in sport tourism and sustainability balanced scorecard leads to development of guidance and assessment criteria for a city to be a sustainable sport tourist destination. This paper aims to present a sport tourism sustainability management model (STSM), consisting of 5 perspectives, namely financial perspective, customer perspective, internal process perspective, learning and growth perspective and sustainability perspective. By using Delphi technique to obtain a consensus from experts, university lecturers, independent organization/association and business entities in relation to sport tourism management, the researcher defines elements to assess complex perspective for sustainable development of sport tourism. The result shows that there are 5 perspectives and 18 elements in relation to sustainable development of sport tourism. All perspectives and elements have high consensus as measured by Kendall’s Coefficient of Concordance (W) of .488. To validate the model, the researcher examines correlation among the five perspectives with structural equation model and finds that the absolute fit is satisfactory, with the value of CMIN/DF at 1.830, RMSEA at .046, GFI at .951, AGFI at .919 and RMR at .038. In addition, the incremental fit also demonstrates positive result with the value of NFI at .962, CFI at .982, TLI at .973 and IFI at .982. As the model aligns and explains empirical data, it can support decision making for management team, effective and efficient strategy drafting for sustainable development in sport tourism and improving livelihoods of residents.

The process of senescence (aging) is largely determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function of senescence, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood’s disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is described.

Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. Some innovative programs, telemedicine and government interest in the prevention of CKD, did not facilitate timely access to care, continuing the increased demand for dialysis and transplants, high morbidity and long-term disability. In contrast, new forms of kidney disease of unknown etiology affected populations in developing countries and underrepresented minorities, who face socioeconomic and cultural disadvantages. With this background, we analyze in the existing literature the effects of social determinants in CKD, concluding that it is necessary to strengthen current kidney health strategies, designing in a transdisciplinary way, a model that considers demographic characteristics integrated into individual risk factors and risk factors population, incorporating the population health perspective in public health policies to improve results in kidney health care, since CKD continues to be an important and growing contributor to chronic diseases.

Covid-19 pandemic lockdown has slow down the world economic system. The pandemic has cleared the roads, close factories and grounded planes causing severe economic challenges. The damaging impact of the pandemic amid lockdown has been a blessing in guise for the environment because of significant drop in pollution level as transport and industrial sectors shutdown. Transport and industrial sectors are major contributors to environmental degradation through various emissions as a result of fossil fuel consumption. Energy consumed by transport and industrial sectors will have to shift to viable, readily available, economically and environmentally friendly with no carbon build up post Covid-19 pandemic. Hydrogen energy remains the best alternative option technologies containing green house gas emission and pollutions of several forms. Hydrogen holds the potential to provide a clean, reliable, renewable and economical source of energy for meeting the growing and unending global energy needs post pandemic. The present paper explores the economic feasibility and potential of hydrogen to serve as a competitive fuel option post pandemic. In this paper, the role of hydrogen as an energy carrier hydrogen economy structure, potential of hydrogen economy, hydrogen production methods, hydrogen application and the economic and environmental importance of hydrogen as a viable fuel option post covid-19 pandemic were discussed. There will be a surge in demand and investment for hydrogen economy post Covid-19.

Electrodynamics is usually written using polarization fields to describe changes in distribution of charge as electric fields change. This approach does not specify polarization fields uniquely from electrical measurements. Many polarization fields will produce the same electrodynamic forces and flows because only divergence of polarization enters Maxwell’s first equation, relating charge and electric field. The curl of any function can be added to a polarization field without changing the electric field at all. The divergence of the curl is always zero. To be unique, models must describe the charge distribution and how it varies. I propose a different paradigm to describe field dependent charge, i.e., the phenomenon of polarization. This operational definition of polarization has worked well in biophysics for fifty years, where a field dependent, time dependent polarization provides gating current that makes neurons respond sensitively to voltage. Theoretical estimates of polarization computed with this definition fit experimental data. I propose that operational definition be used to define polarization charge in general. Charge movement needs to be computed from a combination of electrodynamics and mechanics because ‘everything interacts with everything else’. The classical polarization field need not enter into that treatment at all. When nothing is known about polarization, it is necessary to use an approximate representation with a dielectric constant that is a single real positive number. This approximation allows important results in some cases, e.g., design of integrated circuits in silicon semiconductors, but can be seriously misleading in other cases, e.g., ionic solutions.

Multi-Faith Spaces (MFS) are a relatively recent invention that quickly gained in significance. On the one hand, they offer a convenient solution for satisfying needs of people with diverse beliefs in the institutional context of hospitals, schools, airports, etc. On the other hand, as Andrew Crompton pointed out, they are politically significant because the multi-faith paradigm “is replacing Christianity as the face of public religion in Europe” (2012, p. 493). Due to their ideological entanglement, MFS are often used as the means to promote either a more privatised version of religion, or a certain denominational preference. Two distinct designs are used to achieve these means: negative in the case of the former, and positive in the latter. Neither is without problems, and neither adequately fulfils its primary purpose of serving diverse groups of believers. Both, however, seem to follow the biases and main problems of secularism. In this paper, I analyse recent developments of MFS to detail their main problems and answer the question, whether the MFS, and the underlying Multi-Faith Paradigm, can be classified as a continuation of secularism.

Fashion industry is the second most polluting industry in the world representing a 2 trillion dollars and growing valuation (Pal, 2017). This dual context makes its challenges hard to address. From one side, fashion design education and practice systems have been perpetuating an industrial-focused approach which relies mostly in the economic improvement through fast cycles of product development (Pal, 2017). On the other side, fashion industry has also been closed to either multidisciplinary and transdisciplinary initiatives outside the scope of the artistic disciplines. Therefore, innovative approaches are needed to solve fashion industrial challenges. One of the most promising fields to tackle fashion current environment and technological problems is microbiology (Mazzoto et al., 2021). During the past 50 years, microbiology has played a vital role in solving human grand challenges in health, agriculture, food, and waste management sectors, and it also represents an opportunity for fashion industry as well. Microbiology biotechnological potential for the fashion industry relies mostly on the improvement of toxic waste bioremediation and the development of novel biomaterials and biomolecules. Moreover, the emergent field of synthetic biology is expanding the tools and approaches available, and they can already be seen in the development of engineered living materials that have functional properties (Mazzoto et al., 2021). Despite the urgent need for change, there is still a long way until a more sustainable fashion industry is achieved. Therefore, microbiological research and innovation need maturation to be able to scale-up and reach a global impact for tackling fashion industrial problems.

With the rapid population growth, there is an urgent need for innovative crop improvement approaches to meet the increasing demand for food. Classical crop improvement approaches involve, however, a backbreaking process that cannot equipoise with increasing crop demand. RNA based approaches i.e. RNAi-mediated gene regulation and site-specific nuclease based CRISPR/Cas9 system for gene editing has made advances in the efficient targeted modification in many crops for the higher yield and resistance to diseases and different stresses. In functional genomics, RNA interference (RNAi) is a propitious gene regulatory approach that plays a significant role in crop improvement by permitting down-regulation of gene expression by small molecules of interfering RNA without affecting the expression of other genes. Gene editing technologies viz. clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) have appeared prominently as a powerful tool for precise targeted modification of nearly all crops genome sequence to generate variation and accelerate breeding efforts. In this regard, the review highlights the diverse roles and applications of RNAi and CRISPR/Cas9 system as powerful technologies to improve agronomically important plants to enhance crop yields and increase tolerance to environmental stress (biotic or abiotic). Ultimately, these technologies can prove to be important in view of global food security and sustainable agriculture.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

This article explores the pressing need for a paradigm shift in economics, challenging the dominance of classical economic theories and models that have long held sway. We delve into the limitations of traditional economic paradigms, which often rely on unrealistic assumptions and fail to capture the complexities of human behavior and the modern global economy. Drawing from insights in behavioral economics, environmental economics, and complexity theory, we argue for a more nuanced and multidisciplinary approach to economic analysis. Our discussion addresses the challenges of breaking away from deeply entrenched academic norms and the resistance to change within the economics profession. We highlight strategies for individuals and groups to advocate for the incorporation of modern economic theories in education and research. By fostering interdisciplinary collaboration, encouraging critical thinking, and engaging with policymakers and the public, we aim to catalyze a shift toward economics that is better equipped to address the intricate challenges of the 21st century. This article serves as a call to action for economists and educators alike to embrace a more dynamic and responsive approach to understanding human behavior and decision-making in the modern world.

Staudinger taught us that macromolecules were made up of the covalently bonded monomer repeat units chaining up as polymer chains. The chemical nature of the monomer directed the type of covalent bonds conferring most of the specific properties of the polymer. The more the number of repeat units the longer the chains and the more the possibility for the chains to assume a variety of shapes, from an extended elongated one to a more compact coiled one. Also, the chemical process that resulted in the synthesis of macromolecules produced many chains, often not with the same shape or size. The properties of the polymers improved when the chains became longer but it was more difficult to process them: their viscosity increased with molecular weight; viscosity was no longer an intensive property like it was for small liquids. The main question raised in polymer physics remains: how do these long chains interact and move as a group when submitted to shear deformation at high temperature when they are viscous liquids? This question is debated in a field of polymer physics called RHEOLOGY, whose purpose is to understand the viscoelastic aspects of polymer melts deformation. The current consensus is that we need to distinguish two cases: the deformation of “un-entangled chains” for macromolecules with molecular weight, M, smaller than Me, “the entanglement molecular weight”, and the deformation of “entangled” chains for M > Me. Several eminent scientists have extensively studied these 2 cases over the last 70 years. Paul J. Flory, in 1974, and Pierre-Gilles de Gennes, in 1991, have been awarded the Nobel Price in Chemistry and Physics, respectively, for their significant theoretical contribution to understand these challenging problems. For both of these authors the properties of polymers derive from the statistical characteristics of the macromolecule itself, the designated statistical system that defines the thermodynamic state of the polymer. Me, the molecular weight between entanglements, is defined from the rubber elasticity theory and is known to be equal to Mc/2 where Mc is the molecular weight for the entanglements when viscosity measurements are made. The current paradigm is that the viscoelasticity of un-entangled melts ( M < Mc) is well described by the Rouse model and that the entanglement issues raised by the impact of the increase of the length of the macromolecules on the melt viscoelasticity, when M > Mc, are well understood by the reptation model introduced by de Gennes and co-workers. Both models can be classified in the category of “chain dynamics statistics”. In this paper we examine in details the failures and the current challenges facing the current paradigm of polymer rheology: the Rouse model for M < Mc, the reptation model for M > Mc, the time-temperature superposition principle, the strain induced time dependence of viscosity, shear-refinement and sustained-orientation. The basic failure of the current paradigm and its inherent inability to fully describe the experimental reality is documented in this paper. In the discussion and conclusion of the paper we suggest that a different solution to explain the viscoelasticity of polymer chains and of their “entanglement” is needed. This requires a change of paradigm to describe the dynamics of the interactions within the chains and across the chains. A brief description of our currently proposed open dissipative statistical approach, “the Grain-Field Statistics”, is presented.

The activity of prioritizing software requirements should be done as efficiently as possible. Selecting the most stable requirements for the most important customers for the development company can be a positive factor when we consider that the available resource does not always encompass the implementation of all requirements. Quantitative methods for reaching software prioritization in releases are many in the field of Search-Based Software Engineering (SBSE). However, we show that it is possible to use qualitative Verbal Decision Analysis (VDA) methods to solve this same type of problem. Moreover, we will use the ZAPROS III-i methods to prioritize requirements considering the opinion of the decision-maker, who will participate in this process. Finally, the results obtained in the VDA structured methods were quite satisfactory when compared to the methods using SBSE. A comparison of results between quantitative and qualitative methods will be made and discussed later.

This article sets out to deconstruct and challenge the psychologised and pathologising approach that has come to dominate child protection practice in Aotearoa-New Zealand and comparable societies in neoliberal times. Within a risk and protection focused paradigm circumstances and behaviours associated with material deprivation are construed as indicators of heightened danger and harm as opposed to a means of better understanding family life. In this way, although poverty may be classified as an issue that is worthy of attention in the realm of broader economic and social policy, structural inequality is rendered largely irrelevant to the practice of statutory child protection. This article sets out to trouble this construction. It will be argued that understandings of how the effects of material inequality are played out in the lives of children and their families are critical to the development of more effective child protection social work. This ‘life-world’ is generally populated by young women parenting in poverty. Poverty exacerbates the everyday struggle of parenting - it shames and dis-empowers; reducing confidence and perceptions of competence (Gupta, 2015). A paradigm shift is needed. Child protection policy and practice needs to re-engage with the every-day struggles that accompany the lives of socially marginalised families in increasingly stratified late capitalist society. The future of social work in child protection depends on it.

The manuscript wants to investigate the debate on urban resilience and climate change linking theory and practice, describing the possible innovations that concern urban design, urban normative and regional laws developing in different countries. The approach pursued would encourage resilience and flood protection through smart planning and through the architectural and urban project; considering public space as strategic soil where developing the resilient city, using engineering technical climate defence as new space for citizens and communities. Resilience themes are included in all levels of government and in spatial and strategic development policies such as in some project concerning public and private space and in municipal plans; the urban defense structures has to become new pleasant space for the city; these actions will not only contribute to making cities more resilient but will contribute to the creation of a more pleasant and attractive urban environment. The Resilience is the main keyword of some strategic vision of the Netherlands and of Italian laws and the concept is tested in some best practice such as in Rotterdam, in Bordeaux, in London and in the research carried out by "Arquitectos de Cabecera" in Barcelona. Resilience is seen as a new paradigm of smart planning.

Sweden has long been hailed as a role model in climate policy. But the new right-wing government supported by a far-right populist party is undertaking a paradigm shift in Swedish climate policy and governance. This paper critically analyses this paradigm shift from perspectives of legitimacy, accountability and justice. These are democratic norms important in the analysis of a just transition to climate neutrality. Severe democratic deficits of the policy process and the policies proposed and adopted are identified. The deficits are explained by the neo-corporatist political system of Sweden, the dominance of the (neo)liberal discourse of ecological modernization in Swedish environmental policy, and an ongoing process of autocratization driven by anti-democratic far-right populist parties throughout Europe. The paper ends by suggesting how climate policy and governance can be democratized and re-politicized, that also give room for climate justice advocates to take part in policy processes.

When asked to estimate the carbon footprint of a bundle of relatively low carbon footprint items and relatively high carbon footprint items, people typically report a lower value compared to estimating the high carbon footprint items alone. This finding is called the negative footprint illusion and suggests people report the average rather than sum of the combined items’ carbon footprint. In a recent paper by Gorissen et al. (2024), the authors claimed that people are immune to this illusion if the question is framed differently. Specifically, they found that estimates of the environmental friendliness of a set comprising a burger (high carbon footprint) and an organic apple (low carbon footprint) was higher than for a set comprising the burger alone, whereas no difference was found between the two sets when participants were asked to estimate how environmentally damaging they were. Using larger item categories wherein the degree of the items’ environmental impact is clearly communicated, here we show it does not matter whether participants are required to estimate how friendly or damaging the items are. The roles of attribute substitution, dependent variables, and independent variables (stimulus characteristics) in modulating the negative footprint illusion is discussed.

In this modern era, continuous change is the first step in forming a new structure between theory and practice. The idea of ​​a juggernaut is very relevant to the theory of structuration with current conditions in the 21st century, where technology becomes a reference that can crush anyone who is not responsive to its power. This technology takes one path and takes many roles from various fields: economic, social, political, legal, and educational. This 21st century is marked by great momentum for changes in human behavior and civilization, namely the industrial revolution 4.0 and the arrival of Covid-19, which have changed many social structures and human activities. This makes history a means of connecting the problems in the 21st century with past events. By using a descriptive qualitative method, this paper will reveal how technological developments are very influential on educational and political developments and what are the challenges faced based on historical perspective?. In this case, the study aims to discuss the history and challenges of Indonesia's education system and government system in the 21st century and give a solution. The data used are from 2 books, 14 journal articles, and 4 websites with a span of 2019-2021. The research results are expected to be used as a further study in the face of the development of the modern era in the fields of education and government. This study also has limitations, namely only on the face of the development of the modern era in the fields of education and government.

In vitro fertilization (IVF) has revolutionized the field of assisted reproductive technologies (ART) by offering hope to individuals and couples struggling with infertility. Nevertheless, traditional IVF methods are not exempt from drawbacks, such as suboptimal success rates, intrusive procedures, and ethical considerations. The introduction of micro/nanorobotics in IVF offers a revolutionary chance to tackle these difficulties. This paper presents a short review of the utilization of micro/nanorobotics in IVF, investigating progress in the manipulation of sperm, retrieval of oocytes, culture of embryos, and potential future developments in this fast progressing area. In this discussion, we explore the fundamental concepts, advantages, difficulties, and possible influence of micro/nanorobotics in transforming IVF processes and enhancing patient outcomes.

Abstract Background: Gastric cancer, particularly adenocarcinoma, is a significant global health concern. Environmental risk factors, such as Helicobacter pylori infection and diet, play a role in its development. Purpose: This study aimed to characterize the chemical composition and evaluate the in vitro antibacterial and antitumor activities of AOME. Additionally, morphological changes in gastric cancer cell lines were analyzed. Study design: AOME was analyzed using HPLC-MS/MS and its antibacterial activity against H. pylori was assessed using the broth microdilution method. MIC and MBC values were determined, and positive and negative controls were included in the evaluation. Methods: Anticancer effects were assessed through in vitro experiments using AGS, KATO-III, and SNU-1 cancer cell lines. The morphological changes were examined through SEM and TEM analyses. Results: AOME contained several compounds, including caffeic acid, rutin, and hyperoside. The extract displayed significant antimicrobial effects against H. pylori, with consistent MIC and MBC values of 3.70 ± 0.09 mg/mL. AOME reduced cell viability in all gastric cancer cell in a dose and time-dependent manner. Morphological analyses revealed significant ultrastructural changes in all tumor cells lines, suggesting the occurrence of cellular apoptosis. Conclusions: This study demonstrated that AOME possesses antimicrobial activity against H. pylori and potent antineoplastic properties in gastric cancer cell lines. AOME holds promise as a natural resource for innovative nutraceutical approaches in gastric cancer management. Further research and in vivo studies are warranted to validate its potential clinical applications.

In the last decades, the automatic recognition and interpretation of brain waves acquired by electroencephalographic (EEG) technologies have undergone remarkable growth, leading to a consequent rapid development of Brain Computer Interfaces (BCIs). EEG-based BCIs are non-invasive systems that allow communication between a human being and an external device interpreting brain activity directly. Thanks to the advances in neurotechnologies, and especially in the field of wearable devices, BCIs are now also employed outside medical and clinical applications. Within this context, this paper proposes a systematic review of EEG-based BCIs, focusing on one of the most promising paradigms based on Motor Imagery (MI) and limiting the analysis to applications that adopt wearable devices. This review aims to evaluate the maturity levels of these systems, both from the technological and computational points of view. The selection of papers has been performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), leading to 84 publications considered in the last ten years (from 2012 to 2022). Besides technological and computational aspects, this review also aims at systematically list experimental paradigms and available datasets in order to identify benchmarks and guidelines for the development of new applications and computational models.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

Liquid biopsy via isolation of circulating tumour cells (CTCs) represents a promising diagnostic tool capable of supplementing state-of-the-art for prostate cancer (PC) prognosis. Unfortunately, most of CTC technologies, such as AdnaTest or Cellsearch, critically rely on the Epithelial-Cell-Adhesion-Molecule (EpCAM) marker, limiting the possibility of detecting stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this tontext, dielectrophoresis (DEP) is an epCAM independent, label-free, enrichment system, separating rare cells simply on the basis of their specific electrical properties. As compared to other technollgies, DEP represents a superior technique in terms of running costs, cells yield and specificity, but due to its higher complexity, requires still further technical as well as clinical development. Interestingly, DEP can be improved by the use of microfluid, nanostructured materials and fluoroimaging in order to increase its potential applications. In the context of PC, the utility of DEP can be translated in its capacity to detect CTC in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotypes, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and early diagnosis.

Jakarta is the capital city of Indonesia, which has its own problems in building transportation facilities, especially on land routes. For private vehicle users, congestion is a common thing, given the very dense number of people living in Jakarta, both natives and migrants from outside the region. And for users of public transportation services such as city transportation (angkot) and transjakarta, convenience is the main obstacle. And even though it is a public vehicle, it cannot avoid congestion because it is in one lane with private vehicles except for the transjakarta bus which has its own lane. Meanwhile, for train-based public transportation such as MRT (Mass Rapid Transit), LRT (Light rail Transit), and electric railroad (KRL), the problem is the lack of integration, namely that many stations are not yet integrated with other transportation. Various policies have been implemented to overcome these problems. This study aims to determine the level of effectiveness and efficiency of public transportation in DKI Jakarta today. The method used in this research is qualitative-descriptive through a literature review on 16 journal articles and 4 websites. The results of this study indicate that congestion is a major problem in the means of transportation in Jakarta. This is due to the increase in population due to urbanization which is also accompanied by an increase in the number of private vehicles. Therefore, to overcome this, the Jakarta Provincial Government has made improvements, reforms, and developments in public transportation. And it is hoped that people who originally used private vehicles will switch to using public transportation. But in reality, various problems in public transportation in Jakarta have not been resolved properly. Especially why traffic jams still occur?, and what are the solutions to overcome them?. It is hoped that the results of the findings of this study can be used as a reference in making or designing policies and can contribute to overcoming problems in the transportation sector, especially in the DKI Jakarta area. The limit of this research is that it only focuses on land transportation facilities in Jakarta.

Nursing is a part of health services that serves individuals, groups and communities. In this 21st century the need for nursing services has changed rapidly and in a complex manner. Physical limitations, is on should to be considered, while the implementation and maintenance of patient-centered service infrastructure still have to be recked. The aim of this literature review is to identify the role of telenursing in nursing services for patients. This language method uses literature reviews which are summaries of 10 articles in the publication years of 2019, 2020, and 2021 on 3 search databases, namely Scopus, Science Direct, and SAGE. This review used the new Joanna Briggs Institute and Prisma. The eligibility of these studies were from its title, abstract, research methodology, results, and discussion. The results of the review were presented in narrative form. The results of a review of 10 articles found that the form of nursing services with telenursing could prove long-distance service, time efficiency and funding allocation, but in terms of quality it had been not satisfactory related to its physical implementation of nursing service. Conclusion: The nursing paradigm in the 21st century global era has been developed with the help of technology to meet the needs of distance efficiency and cost limitations. Thus, telenursing is a solution to answer these challenges.

This paper presents a configuration of dual output single phase current source inverter with 6 switches for microgrid applications. The inverter is capable of delivering power to two independent set of loads of equal voltages or different voltages at the load end. The control strategy is based on Integral Sliding Mode Control (ISMC). The remote monitoring of the inverter is performed with cyber infrastructure. The cyber physical test bench is developed based on Reconfigurable I/O processor (NI MyRIO-1900) for control and monitoring of the inverter. The inverter prototype is tested in cyber physical test bench in laboratory conditions. The performance of the inverter is analyzed and monitored through the remote system. Also, the inverter is analyzed with different voltage conditions.

Understanding how the public perceives various risks and hazards associated with our well-being and health is crucial for government and policymakers. The present research aimed to assess the public's perception of various risks and hazards associated with their well-being and health. The study combined two well-known approaches to risk assessment, namely, the analytical hierarchical process (AHP) and the psychometric paradigm. Seven risk attributes were chosen from the risk perception literature to evaluate 27 risks and hazard activities using a survey questionnaire developed based on the psychometric paradigm literature. The collected data was then analyzed using AHP to determine the priority weight for each risk attribute. The results showed that the most important risk attribute was voluntariness of risk, followed by chronic-catastrophic and newness of risk. Furthermore, the study found that natural hazards were ranked the highest, followed by refugee influx and fire hazards. In contrast, the mobile phone was perceived as the lowest type of risk. The findings can be used by policymakers to develop effective and sustainable risk communication strategies. Policymakers can use the research findings to create effective and sustainable risk communication strategies that help the government to inform and educate the public about potential risks, improve coordination among agencies and stakeholders, and enhance public trust in government decision-making.

Nowadays, it can be observed that all kinds of technology are gradually being incorporated to assist the human being in the performance of their frequent and daily tasks. Technological tools provide means to facilitate, improve, help and support any activity which, in itself, may be complicated, either because of the difficulty involved in carrying it out, or because the person carrying it out has limited capabilities due to the environment not being prepared for their abilities and skills. In this sense, Special Education is currently receiving special attention from researchers, especially those aimed at children. Although the proposals that have appeared recently provide perfect solutions to improve educational processes with ingenious didactic applications, there is still an interesting line of study on how to interact with these younger people in these educational processes. In this sense, haptic technologies can play a very important role, complementing all these solutions by incorporating tools that facilitate direct contact with people, especially in their initial stages, which are the most complicated. This paper aims to provide an overview of haptic technologies and how they present solutions that can be integrated into the aforementioned educational processes.

The advent of the digital age has brought about significant transformations in the entertainment industry, challenging traditional paradigms and redefining the ways in which content is created, distributed, and consumed. This research paper critically reviews the paradigm shift occurring in the entertainment industry, focusing on the implications of digital technologies, the rise of online platforms, changing consumer behavior, and the impact on various stakeholders. By analyzing relevant literature, industry reports, and case studies, this paper aims to comprehensively understand the challenges and opportunities presented by the digital age and assess its impact on the entertainment industry.

Independent Learning Independent Campus (MBKM) is a program to develop an educational ecosystem that is in harmony with learning in higher education and the needs of industry. The limited link and match between universities and the business and industrial world in Indonesia are obstacles in realizing Indonesia as a developed country in the Industrial Revolution 4.0 era. The purpose of this study is to analyze the impact of the Independent Learning Independent Campus (MBKM) program on improving the performance of Ibn Khaldun University Bogor. The method used in this study is descriptive statistics with quantitative analysis. The sample that participated in this study consisted of all active students, lecturers, and administration staff. The research data was obtained through distribution to 6100 students, 233 lecturers, and 150 education staff. The research stages include socializing the understanding of MBKM, filling out the survey, calculating the distribution of respondents' filling, and concluding the assessment category using the weighted mean score (WMS) method. Based on the result, the implementation of MBKM in University of Ibn Khaldun Bogor based on all indicators can conclude that MBKM improve the performance of Ibn Khaldun Bogor University in the good category with an average percentage assessment criteria above 75%

Novel molecular pinball machines of the plasma membrane control cytosolic Ca²⁺ levels that regulate plant metabolism. [https://youtu.be/zABg7LiBk88] Essential components involve: 1. an auxin-activated proton pump; 2. arabinogalactan glycoproteins (AGPs); 3. Ca²⁺ channels; 4. auxin-efflux “PIN” proteins. Typical pinball machines release pinballs that trigger various sound and visual effects. However, in plants “proton pinballs” eject Ca²⁺ bound by paired glucuronic acid residues of numerous glycomodules in periplasmic AGP-Ca²⁺. Freed Ca²⁺ ions flow down the electrostatic gradient through open Ca²⁺ channels into the cytosol thus activating numerous Ca²⁺-dependent activities.Clearly cytosolic Ca²⁺ levels depend on activity of the proton pump, the state of Ca²⁺ channels and size of the periplasmic AGP-Ca²⁺ capacitor: Proton pump activation is a major regulatory focal point tightly controlled by the supply of auxin: auxin efflux carriers conveniently known as “PIN” proteins [null mutants are pin-shaped!] pump auxin from cell to cell. Mechanosensitive Ca²⁺ channels and their activation by reactive oxygen species (ROS) are yet another factor regulating cytosolic Ca²⁺.Cell expansion also triggers proton pump/pinball activity by mechanotransduction of wall stress via Hechtian adhesion thus forming a Hechtian oscillator that underlies cycles of wall plasticity and oscillatory growth.Finally, Ca²⁺ homeostasis of plants depends on cell surface external storage as source of dynamic Ca²⁺, unlike the internal ER storage source of animals where the added regulatory complexities ranging from vitamin D to parathormone contrast with the elegant simplicity of plant life. This paper summarises a sixty year Odyssey.

New technologies such as "connected" and "autonomous" vehicles are going to change the future of traffic signal control and management and possibly will introduce new traffic signal systems that will be based on floating car data (FCD). The use of floating car data to regulate, in real-time, traffic signal systems has the potential for an increased sustainability of transportation in terms of energy efficiency, traffic safety and environmental issues. However, research has never explored how not "connected" vehicles would benefit by the implementation of such systems. This paper explores the use of floating car data to regulate in real-time traffic signal systems in terms of cooperative-competitive paradigm between "connected" vehicles and conventional vehicles. In a dedicated laboratory, developed for testing regulation algorithms, results show that "invisible vehicles" for the system (which are not "connected") in most simulated cases also benefit when real time traffic signal settings based on floating car data are introduced. Moreover, the study estimates the energy and air quality impacts of signal regulation by evaluating fuel consumption and pollutant emissions. Specifically, the study demonstrates that significant improvements in air quality are possible with the introduction of FCD regulated traffic signals.

We propose a theory of ASD as a condition of comorbid cognitive impairments that corrupt the learning, encoding, and manipulation of episodic and semantic memories. We consider (i) episodic and semantic memory functions of the entorhinal-hippocampal complex, (ii) constraints on the transfer and encoding of these memory components into neocortical areas, and (iii) the demands of cognitively manipulating memories in distributed computations being necessary for goal oriented interactions. In ASD, learning and cognitive challenges manifest in diverse ways but especially in high-complexity model predictive control tasks with latent variables. ASD impairments in social interactions represent a prototypical example. Social interactions are at the high end of complexity and require processes (i)–(iii) to work in a concerted fashion due to the need for the learning and estimation of many, sometimes latent, parameters, including emotions, intention, physical and mental capabilities as well as the predictive modeling of these parameters for decision making and timed-action series. We put forth the idea that autism is a result of an arbitrary combination of otherwise not prominent corruptions in processes (i)–(iii). Together, these corruptions may severely impair intelligence and slow down learning, especially in high complexity learning tasks. Over time, slow learning may spare the spontaneous learning-by-doing method - namely, repetitive behavioral patterns, whereas behavioral failures related to complex tasks can restrict interest in such task, thus inducing a fear of novelty; conversely, the fear of novelty restricts interest and can slow learning down. We embed our thoughts into a predictive autoencoding, goal-oriented model of a deterministic world. We compare this model to others, such as the noisy brain model, the Bayesian prior theory, the mirror neuron theory and the weak central coherence theory. We argue that the predictive autoencoder model of the deterministic world harmonizes with these other models and embraces them in a straightforward way.

Through the process of paradigm change (water as a resource towards water as a common), the authors examine, from a theoretic point of view, the water governability proposed by Agenda del Agua Cochabamba (AdA) – Cochabamba Water Agenda – in the Cochabamba Valley (Bolivia), identifying barriers and drivers to the process that could take place. The rise of Evo Morales in Government in 2006 suggested that policy making would somehow take a fundamental turn resulting in more poor environmental-oriented water policies. However, if that was indeed the case, the implementation of these policies remain controversial as strong power asymmetries still exist at a local level that interfere with national policies shaping the political area. The Cochabamba Water Agenda echoes this debate on the political arena and contributes a politically contested water management through a paradigm change envisaging the difficulties through its implementation. The question remains if this “political” solution to paradigm change in water management may reduce water conflicts.

Microarray gene expression-based detection and classification of medical conditions have been prominent in research studies over the past few decades. However, extracting relevant data from the high-volume microarray gene expression with inherent nonlinearity and inseparable noise components raises significant challenges during data classification and disease detection. So, this paper proposes a two-level strategy involving feature extraction and selection methods before the classification step. The feature extraction step utilizes Short Term Fourier Transform (STFT), and the feature selection step employs Particle Swarm Optimization (PSO) and Harmonic Search (HS) metaheuristic methods. The classifiers employed are Non-Linear Regression, Gaussian Mixture Model, Softmax Discriminant, Naive Bayes, SVM (Linear), SVM (Polynomial), and SVM (RBF). The two-level extracted relevant features are compared with raw data classification results, including Convolutional Neural Network (CNN) Methodology. Among the methods, STFT with PSO feature selection and SVM (RBF) classifier produced the highest accuracy of 94.47%.

This article discusses how, in today’s world of disruptive and dramatic social change (DSC), non-sports related coaching, which includes a wide range of services such as life coaching, career coaching, executive coaching, and team coaching, can inadvertently fuel undesirable social dynamics. There is little or no awareness of this risk among coaches and coachees. The global, fast-growing, multi-billion-dollar industry aimed at supporting people and organisations to perform better and increase wellbeing while managing and adapting to change has been developed with limited sociological input. The article is based on 15 years of social constructionist-informed reflective practice by a sociologist-turned-coach, and uses a multi-layered autoethnographic account to argue for a sociologically informed paradigm shift in coaching, as well as relevant sociological knowledge and social and human sciences research methodology in coaches’ education. It presents the rationale and key features of a new coaching approach that places DSC-relevant sociological concepts at the heart of the coaching process, helps people develop psycho-sociological awareness, and uses a learning-to-develop through research design. A new definition of coaching to address DSC is derived. Coaching practitioners will find DSC-relevant sociological concepts, critical reflections, coaching questions, and procedures to expand coaching effectiveness. Interdisciplinary research topics combining coaching sociology and coaching psychology are suggested.

Zearalenone is one of the most prevalent estrogenic mycotoxins produced mainly by Fusarium family fungi, and harmed the heath of animals. Zearalenone hydrolase is an important enzyme capable of degrading zearalenone into a non-toxic compound. Although previous research has investigated the catalytic mechanism of zearalenone hydrolase, information on its dynamic interaction with zearalenone remains unknown. This study aimed to develop a pipeline for identifying the allosteric pathway of zearalenone hydrolase. Using an identity analysis, we identified hub genes whose sequences can generalize a set of sequences in a protein family. We then utilized a neural relational inference (NRI) model to identify the allosteric pathway of the protein throughout the entire molecular dynamics simulation. The production run lasted 1 microsecond, and we analyzed residues 139-222 for the allosteric pathway using the NRI model. We found that the cap domain of the protein opened up during catalysis, resembling a hemostatic tape. We used umbrella sampling to simulate the dynamic docking phase of the ligand-protein complex and found that the protein took on a square sandwich shape. Our energy analysis using both MMPBSA and PMF analysis showed discrepancies, with scores of -8.45 kcal/mol and -1.95 kcal/mol, respectively. MMPBSA, however, obtained a similar score to that of a previous report.

Indonesia is an archipelago with diverse ethnicities, races, languages, cultures, beliefs, and customs. As Indonesians, with these differences, they should respect each other, or what is commonly known as tolerance. However, in the 21st century, tolerance between people in Indonesia is starting to fade. This is due to the development of the times accompanied by technology development, which causes globalization to enter quickly. The culture of tolerance typical of Indonesian society is starting to fade due to the influence of globalization. Based on these problems, this study aims to determine what causes the decline intolerance of Indonesian society in the 21st century and answer what solutions can be given to prevent the decline intolerance of Indonesian society in the 21st century. The research method used is descriptive-qualitative through literature review by analyzing data following the topic to be discussed. The data used are from 20 journal articles with a span of 2019-2021. The results of this study are in the form of a decline in intolerance that the Indonesian people own due to technological advances in the form of adverse use of social media. However, with the existence of moral education and the role of teachers and the government to overcome the decline intolerance, it is hoped that the Indonesian people will understand the meaning and importance of tolerance. This study also has limitations, namely only on the causes of the fading of tolerance in Indonesian society.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and the risk of a major cardiovascular event is highest among those with established disease. Ongoing management of these patients relies on the accurate assessment of their response to any prescribed therapy, and their residual risk, in order to optimize treatment. Recent international guidelines and position statements concur that the plasma concentration of apolipoprotein B (apoB) is the most accurate measure of lipoprotein associated ASCVD risk. This is especially true for the growing number of individuals with diabetes, obesity or the metabolic syndrome, and those on statin therapy. Most guidelines, however, continue to promote LDL-C as the primary risk marker due to uncertainty as to whether the greater accuracy of apoB is sufficient to warrant a paradigm shift. Recommendations regarding apoB measurement vary, and the information provided on how to interpret apoB results is sometimes insufficient, particularly for the non-lipid specialist. Misinformation regarding the reliability of the assays is also frequently repeated despite its equivalent or better standardization than many other diagnostic assays. Thus, demand for apoB testing is relatively low, which means there is little incentive to increase its availability or reduce its cost. In this review, we examine the results of recent clinical outcomes studies and meta-analyses on the relative values of apoB, LDL-C and non-HDL-C as markers of ASCVD risk. Although there is seemingly minimal difference among these markers when only population-based metrics are considered, it is evident from our analysis that, from a personalized or precision medicine standpoint, a great many individuals would benefit, at a negligible total cost, if apoB measurement were better integrated into the diagnosis and treatment of ASCVD.

According to known laws of physics, chronic positive mass balance is the actual etiology of obesity, not positive energy balance. The relevant physical law in terms of body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. A recently proposed mass balance model (MBM) describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best human experimental feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this disease may follow in the near future. The purpose of this article is to present the core issues of the upcoming paradigm shift as well as some practical applications related to the topic.

We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.

Breast cancer (BC) is the most common malignancy and the second cause of cancer specific death in women from high-income countries. More than 70% of all breast cancer are hormone receptor-positive BC, and elevated estrogen circulating in blood has been proved to be a strong risk for BC development. This is due to its contribution to enhance proliferation of cancerous cells, angiogenesis and metastasis stimulation and therapy resistance. The estrogen (E) metabolism–gut microbiome axis is functional with underlying individual variations in E levels. It is reasonable that the estrobolome (bacterial genes whose products are capable of metabolizing E) could contribute to the risk of hormone-driven malignancies including BC and may serve as a potential biomarker and target. Gut microbial β -glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to contribute to hormone breast cancer. In this review, we discuss the recent knowledge about the role of GUS enzyme in the pathogenesis of breast cancer. We focus on the role of GUS in (i)-the microbioma and estrogen metabolism, (ii) diet, estrobolome, and the BC development, (iii) other activities of the bacterial β-glucuronidase, and (iv) the new molecular target for BC therapeutic application.

The stochastic modelling of chemical physical processes is essentially based on a coarse-grained formulation of fluctuations, usually described by means of Wiener processes. By taking the paradigmatic example of chemical reaction kinetics, we propose a simple representation of microscopic stochastic dynamics grounded on the use of distributional derivatives of counting processes that account for elementary reactive events. This approach is consistent with the statistical analysis based on the Chemical Master Equation, and provides the formal setting for the existing algorithmic approaches (Gillespie algorithm). Some practical advantages of this formulation are addressed, and several other examples are discussed in connection with cluster formation, velocity fluctuations in liquid systems, and quantum transitions (radiative interactions) at the molecular level.

A vast majority of the countries is under the economic and health crises due to the current epidemic of coronavirus disease 2019 (COVID-19). The present study analyzes the COVID-19 using time series, which is an essential gizmo for knowing the enlargement of infection and its changing behavior, especially the trending model. We have considered an autoregressive model with a non-linear time trend component that approximately converted into the linear trend using the spline function. The spline function split the COVID-19 series into different piecewise segments between respective knots and fitted the linear time trend. First, we obtain the number of knots with its locations in the COVID-19 series and then the estimation of the best-fitted model parameters are determined under Bayesian setup. The results advocate that the proposed model/methodology is a useful procedure to convert the non-linear time trend into a linear pattern of newly coronavirus case for various countries in the pandemic situation of COVID-19.

Swift and diligent resilience response is mandatory in sustainable geo-distributed ecosystems. The real-time geo-spatial resilience requires agility in millions of parallel and distributed data processing tasks on data acquired from regional condition monitoring(RCM) systems. These tasks include expiditous resolution of complex sustainability conflict sets, promptly anomalies characterization in chaos sets, and resilience response uniqueness. This work is an archetype of a paragon geo-resilience support system(GRSS) for regional sustainability using a novel melioration in DADO production machine. The proposed expert system capitalized the synergic strengths of RETE, TREAT, LEAPS and GATOR networks was designed and implemented as a synthetic DADO machine(SDM). The generic architecture of DADO machine was improved in this work by enrichment in rule set conditions and solution set for regional scale resilience rule set conditions. The condition left-hand side(LHS) X equal to the solution set 2X for right-hand side (RHS) was the goal achieved by working memory(WM) optimization and conflict resolution strategy(CRS) in alpha and beta networks rules. A round-trip time of 80.2 seconds for first event response set using 1492 segment size and sequence number 360,000 with maximum packets at a single geospatial structure was 21 packets/sec was a noticeable landmark in this work. LEAPS and Concurrent-read algorithm for GATOR cluster networks in the proposed synthetic DADO machine architecture was the overall implementation that enabled urban scale resilient system practically possible on physical SHM deployment.

Location-Based Services (LBS) have been widely deployed for the connected vehicle (CV) applications such as vehicle navigation,vehicle tracking and location-based augmented reality. The current LBS deployments have limitations in supporting time-critical CV use cases, including vehicle to vehicle (V2V), vehicle to infrastructure (V2I) and vehicle-to-people (V2P) safety applications. The paper presents the new LBS framework based on the publish-subscribe communication paradigm, to enable device-to-device (D2D) connections through use of selected application protocols in the application layer of the TCP/IP layered protocol model. Two publish-subscribe application protocols, Distributed Data Service (DDS) real-time publish and subscribe (DDS-RTPS) and Message Queue Telemetry Transport (MQTT), are introduced to support the LBS D2D applications. A number of test scenarios with Mosquitto MQTT and OpenDDS under 4G-mobile broadband (MBB) services are designed to assess the transmit/receive round-trip time (RTT) and packet-loss rate (PLR) with settings of a publisher to multiple subscribers, to simulate the connections to multiple vehicles. The transmission frequency is set for 10 Hz and the message sizes vary from 100 to 2000 Bytes. The PLRs are defined as the percentages of the delayed messages beyond a delay limit. Static test results with OpenDDS show that for the RTT delay beyond the limit of 100 ms, the total PLRs range between 5.25% and 8.76% for the message size of 50 to 2000 Bytes. Vehicle testing results with Mosquitto show that PLRs for the RTT delays between 200 ms and 1000 ms are 0.63%, 3.58% and 5.77%, for connections with 1, 4 and 10 vehicles, respectively. The results demonstrate the potential of the D2D LBS framework for medium-demanding CV safety applications such as V2P and V2I use cases, taking advantages of the 4G-MBB services and 5G extreme mobile broadband (eMBB) services and mobile devices generally available with all road users.

In the European Union, the eCall system has been mandatory since March 31, 2018. The system enabled a significant increase in safety on roads and highways, making help faster in the event of an accident. However, based on circuit-switched 2G/3G communications and an onboard device called IVS, it is generally unavailable on legacy vehicles. Some of its limitations tend to be remedied by the future NG eCall based on 4G/5G packet-switched communications. This paper discusses why IVS may be an Achilles’ heel of any future IVS-based eCall and analyzes the advantages of a smartphone-based system. The TEZE system, implemented and installed in Italian highway tunnels, is a first general-purpose safety system, and allows highly reliable smartphone-based emergency calls. It is based on a dedicated low-cost ground infrastructure that allows monitoring of the availability of emergency call service through the mobile radio networks of the operators present inside the tunnels. The system complies with the ISO/IEC 30141:2018 reference standard. Identifying functional/non-functional requirements and their verification criteria provide an overall validation of the analyzed system. The paper concludes by examining some key functionalities for vehicular services that can be implemented in an integrated system based on smartphones and heterogeneous networks.

Matter grows and self-assembles to produce complex structures such as virus capsids, carbon fullerenes, proteins, glasses, etc. Due to its complexity, performing pen-and-paper calculations to explain and describe such assemblies is cumbersome. Many years ago, Richard Kerner presented a pen-and-paper path integral approach to understand self-organized matter. Although successfully addressed many important problems including the yield of fullerene formation, the glass transition temperature of doped chalcogenide glasses, the fraction of boroxol rings in B2O3 glasses, the first theoretical explanation for the empirical recipe of window and Pyrex glass and the understanding of virus capsid self-assembly, still is not the primary choice when tackling similar problems. The reason lies in the fact that it diverges from mainstream approaches based on the energy landscape paradigm and non-equilibrium thermodynamics. In this context, a critical review is presented, demonstrating that the Richard Kerner method is, in fact, a clever way to identify relevant configurations. Its equations are simplified, common physical sense versions to those found in the energy landscape kinetic equations. Subsequently, the utilization of equilibrium Boltzmann factors in the transition Markov chain probabilities is analyzed within the context of local two-level energy landscape models kinetics. This analysis demonstrates that their use remains valid when the local energy barrier between reaction coordinate states is small compared to the thermal energy. This finding places the Richard Kerner model on par with other more sophisticated methods and, hopefully, will promote its adoption as an initial and useful choice for describing the self-agglomeration of matter.

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma (ccRCC) samples were re-analyzed from the Genomic Fabric Perspective that considers the transcriptome a multi-dimensional mathematical object, constrained by a dynamic set of expression correlations among genes. Every gene in the chest wall metastasis (MET), two primary tumors (PTA, PTB) and the surrounding normal tissue (NOR) of the right kidney was characterized by three independent measures: average expression level (AVE), relative expression variation (REV) and expression correlation (COR) with each other gene. AVE was used to determine the regulation of the genomic fabrics of ccRCC, apoptosis, chemokine and VEGF signaling pathways. REV quantified the alteration of the transcripts’ abundances control, while COR determined the remodeling of the transcriptomic networks of chemokine signaling and oxidative phosphorylation genes. The gene hierarchy was established in based on Gene Commanding Height and the Gene Master Regulators (GMR) TASOR (PTA), FAM27C (PTB) and ALG13 (MET) and DAPK3 (NOR) were identified in each profiled region. We predict that TASOR overexpression would block transcription in PTA but not in PTB, while slightly stimulating it in NOR. Silencing of ALG3 would slow-down the cell-cycle in all three cancer regions with practically no effect in NOR.

This paper presents a hybrid modelling approach that combines physics-based electromigration modelling (PEM) and statistical methods to evaluate the electromigration (EM) limits of nano-interconnects in mesh networks. The approach, which is also compatible with standard Place and Route (P&R) tools and practices, takes into account the positive impact of network redundancy on EM current limits. The study shows that conventional methods underestimate the EM current limits of a power delivery network (PDN) unit-cell by 80% due to their lack of consideration for redundancy. Additionally, the time-to-failure (TTF) distributions of a PDN unit-cell adhered to a lognormal distribution, where the lognormal sigma, σlogn, exhibits a 55% reduction compared to that of the single constituent interconnects. The study also found the negative voltage (i.e. ground or Vss) grid to be more susceptible to EM than the positive voltage, i.e. Vdd grid. In the examined grid unit-cell design, both the number of interconnect sites prone to voiding and also the magnitude of the peak tensile stress within the nano-interconnects were found to be 2-folds as high in the Vss case compared to Vdd. lognormal sigma of TFF for the grid unit-cells, σ_(logn-tile), show a marked reduction compared to the lognormal sigma of the constituent single interconnects, σ_logn, with a 50% and 66% decrease compared to single interconnects, for downstream (Vss) and upstream (Vdd), respectively. In addition, σ_(logn-tile) was 3-folds higher for downstream (Vss) compared to upstream (Vdd), whilst, in contrast this difference was only 2-folds at single interconnect level. 4.13-folds higher TTF50% was observed at grid unit-cell level for upstream compared to downstream operation which was also more pronounced than in the single interconnect level where the difference was only 2-folds. This research provides valuable insights into EM aging of nano-interconnects in mesh networks and could pragmatically enhance the accuracy of EM compliance evaluation methods.

There are two major proposed forms of dark energy: the cosmological constant and the quintessence scalar field. However, the former has the cosmological constant problem and the latter does not have observational evidence to support the theory. In this paper, we propose a dark energy paradigm to solve the cosmological constant problem and to predict lepton masses as evidence. The dark energy paradigm is a unified dark sector that is based on Planck's dimensional analysis, Lambda CDM, energy conservation, and force equilibrium. We find that dark energy can vary from the cosmological constant to the Planck scale. We find that the predicted values of lepton masses based on the dark energy paradigm agree with the observed values to 1% (or within error ranges).

Prostate cancer is the most occurred malignant disease in the male population in over one-half of the countries and still constitutes the fifth leading cause of death in 2020, worldwide. Metastatic prostate cancer is a lethal malignancy that mostly is terminated within several years through the patient's death. Researchers should focus on the phenomenon which is rigorously appertaining to metastatic cascade and operating as an initiator of metastases to provide the knowledge needed to solve the problem of diagnostics and treatment of advanced prostate cancer patients. The epithelial-mesenchymal transition is one such phenomenon. The current review is based mainly on three papers published in 2021, which describe the most important tissue-specific factors managing epithelial-mesenchymal transition and are discussed with scientific papers published in acknowledged journals. The effect of the current review is the specification of profiles of precise tissue factors predicting the progression of the prostate neoplasm to its metastatic stage in a new edition.

Resilience is an adaptive coping mechanism needed by health workers, especially nurses who have longer working hours than other health workers to provide care to patients in the era of the Covid-19 pandemic which is a global health problem. The aim of this literature review is to identify the resilience of nurses during the covid-19 pandemic the 21 st century global nursing paradigm. This language method uses literature reviews which are summaries of 10 articles in the publication years of 2020-2021 on search 4 databased electronic searches contain namely Scopus, ProQuest, Pubmed, and Scient Direct. This review used prisms. The eligibility of these studies were from its title, abstract, research methodology, results and discussion. The results of the review were presented in narrative form. The results of a review of 10 articles found that the form of psychological factors during the covid-19 pandemic, mental distress and influencing factors in nurses caring for patients with COVID-19, resilience nurses during the covid-19 pandemic. Conclusion: The 21 st century global nursing paradigm, one of the global problems in the health sector, with the outbreak of the corona virus disease (Covid-19), the role of nurses as the front guard is needed by the community to provide health services in line with the increasing incidence of covid-19 cases. Strong nurses need an adaptive inner coping mechanism.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.

Background: Nursing services provided by nurses are based on knowledge and competence in the field of nursing science developed in accordance with Client needs, scientific developments, and the demands of globalization. These health services include nursing services that are carried out responsibly, accountably, with quality, and safely by nurses who have obtained registration and permission to practice. Nursepreneur is innovation and courage to take risks and is ready to work hard to achieve goals with optimism. Which has important components namely: 1) quality, 2) role, 3) option and success. The post-pandemic new world, especially in the health care system, continues to grapple with the demands of costs to provide patient care and safety. By using the application of the nursing theory model. Purpose :. Assessing scientific studies on the application of evidence-based intervention in wound care using nursing theory, identifying the important role of telenursing in improving nursing services in Nerspreneurship, Method: literature study Conclusion: Telenursing in nursing focuses on providing nursing care through information technology, such as telephone, computers, and the Internet that can be used to improve treatment outcomes among older people, especially those with low literacy skills and low financial status (Esmaeilpour-BandBoni et al., 2020). The statement from the results of the study refutes that Telenursing is intended for patients who have higher education and middle and upper economic states.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

There is less attention to use an environmental perspective in economic valuation and individuals' willingness to pay for recreational sites. Therefore, the aim of this study is to use contingent valuation methods to estimate the recreational value and willingness to pay of visitors to the protected area of Helen forest, considering the scale of the new environmental paradigm (NEP). To achieve this, the sample size for survey was determined using the Cochran method, and then economic valuation and environmental perspective questions were designed and completed through the completion of a dual-dimensional questionnaire and NEP scale. To determine the factors influencing individuals' willingness to pay, the logistic regression model was employed. In this study, two modeling approaches were used. The first utilized a base model containing socio-economic variables, while the second model integrated a NEP into the base, and subsequent estimations were conducted. The results indicated that 83.04% of visitors are willing to pay an amount for the recreational use of the study area. The estimated model results demonstrated that variables such as the proposed amount, frequency of visits, environmental statement, age, gender, education, individual monthly income, residency, and the NEP are among the most influential factors affecting the likelihood of accepting the proposed amount by tourists. The strong and positive correlation between the NEP and willingness to pay indicates that individuals with a favorable environmental perspective tend to exhibit a higher willingness to pay. In this study, the average willingness to pay per household per visit was 199,793 Rials, and the annual recreational value for the entire Helen forest area was 23746832564 Rials. Furthermore, the survey results regarding visitors' perspective on the NEP revealed that the average NEP score for visitors to Helen forest was 36.57, with the statement 'plants and animals have similar rights to humans' receiving the highest average score of 28.4. The result of this study shows the importance of environmental perspective for sustainable management of a recreational site to balance economic development with environmental conservation and social well-being.

The key to building a strong bridge country lies in talent, and the foundation lies in education. The cultivation of bridge engineering talents is related to the future and destiny of building a strong bridge country. This course adopts the educational philosophy of "holographic teaching method" centered on the comprehensive development of students, cultivating "engineering thinking" guided by engineering education certification, enhancing "abilities and qualities" through professional knowledge, reconstructing the course knowledge content system through engineering philosophy thinking, and implementing the ideological and political construction of the course in a multi-level unified manner of "explicit + implicit". Based on restructuring the course content system, we will strengthen the construction of diversified course resources, integrate theory with practice throughout the entire process of the course, practice the concept of "bridge architects + bridge engineers" parallel development, and cultivate cross-border and compound talents with comprehensive qualities of "engineering + art + humanities".

Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

This concept paper explores possible collective identities for a future wildland fire workforce. Taking inspiration from the work of futurists who foresee an end to the dominant fire exclusion/suppression paradigm, and assuming an emerging fire restoration/resilience paradigm shift replaces it, the paper engages in speculative explorations of the process and product of this paradigm shift on future collective identities for a workforce doing ecological fire management. Social constructionist assumptions from symbolic interactionist sociological theory, Gramscian political theory's concept of hegemony, and New-Social-Movement theory's concept of collective identity all provide the intellectual foundations for the discussion. This concept paper argues that in order to actualize a paradigm shift, more than advances in scientific research or reforms of government policies will be required--the wildland fire community will need to become (or join) a social movement engaged in collective actions. An imaginary social movement, the "Greenfire revolution," is invented to help illustrate how the selected theories and concepts might apply in the social construction of ecological fire management and the collective identities of its future workforce.

Early prediction of thermal loads plays an essential role in analyzing energy-efficient buildings' energy performance. On the other hand, stochastic algorithms have recently shown high proficiency in dealing with this issue. These are the reasons that this work is dedicated to evaluating an innovative hybrid method for predicting the cooling load (CL) in buildings with residential usage. The proposed model is a combination of artificial neural networks and stochastic fractal search (SFS-ANN). Two benchmark algorithms, namely the grasshopper optimization algorithm (GOA) and firefly algorithm (FA), are also considered to be compared with the SFS. The non-linear effect of eight independent factors on the CL is analyzed using each model's optimal structure. Evaluation of the results outlined that all three metaheuristic algorithms (with more than 90 % correlation) can adequately optimize the ANN. In this regard, this tool's prediction error declined by nearly 23, 18, and 36 % by applying the GOA, FA, and SFS techniques. Also, all used accuracy criteria indicated the superiority of the SFS over the benchmark schemes. Therefore, it is inferred that utilizing the SFS along with ANN provides a reliable hybrid model for the early prediction of CL.

Because the application of antibiotic growth promoters (AGP) causes accelerated adverse effects on the animal diet, the scientific community has taken progressive steps to enhance sustainable animal productivity without using AGP in animal nutrition. Organic acids (OAs) are non-antibiotic feed additives and a promising feeding strategy in the swine and broiler industry. Mechanistically, OAs improve productivity through multiple and diverse pathways: (a) reduction of pathogenic bacteria in the gastrointestinal tract (GIT) by reducing the gut pH; (b) boosting the digestibility of nutrients by facilitating digestive enzyme secretion and increasing feed retention time in the gut system; (c) having a positive impact and preventing meat quality deterioration without leaving any chemical residues. Recent studies have reported the effectiveness of using encapsulated OAs and synergistic mechanisms of OAs combinations in swine and broiler productivity. On the other hand, the synergistic mechanisms of OAs and the optimal combination of OAs in the animal diet are not completely understood, and further intensive scientific explorations are needed. Moreover, the ultimate production parameters are not similar owing to the type of OAs, concentration level, growth phase, health status of animals, hygienic standards, and environmental factors. Thus, those factors need to be considered before implementing OAs in feeding practices. In conclusion, the current review evaluated the basics of OAs, mode of action, novel strategies to enhance utilization, influence on growth performances, nutrient digestibility, quality traits, and meat preservation of swine and broilers and their potential concerns regarding utilization.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.