The Embodied Cognitive Behavior Therapy (ECBT) approach for the treatment of emotional disorders in clinical settings is presented. The model integrates cognitive behavioral theory, neuroscience and embodied cognition. ECBT draws from evidence of bidirectional effects between modes of bottom up (sensori-motor simulations giving rise to important basis of knowledge) and top down (abstract mental representations of knowledge) processes in psychotherapy. The paper first describes the dominance of the traditional mentalistic view of cognition and its limitations. Evidence for the embodied model of cognition and emotion is reviewed whilst highlighting its advantages as a complimentary process model to deepen and broaden talking therapies. An overview is given of the switch (e.g., the technique of balancing) between top-down and bottom-up orientation in the ECBT model as well as a clear description of the method for emotional regulation, acceptance of unwanted emotions and emotional mastery. ECBT builds on and extends the unconscious processes of the ‘Interpersonal Synchrony’ (IS) model identified by Koole and Tschacher [1], to enhance the therapeutic alliance for emotional co-regulation. A new idea is proposed that both embraces and extends the IS model: embodiment techniques of imitation and movement synchronization in the Emotional Field of our method be used in a conscious way to speed up the calming effects of co-regulation and the client’s self-regulatory capacity. The paper ends with an outline of the criteria needed to become an embodied therapist. A case study is given highlighting these aspects.

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by antioxidant defense systems. Cells produce ROS as a control of physiological processes, but increasing ROS becomes pathological leading to non-specific and irreversible damage to biological molecules, such as DNA, lipid, and protein. Endogenous ROS are mainly produced by mitochondria during both physiological and pathological conditions, and enzymes, such as nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO) and monoamine oxidase (MAO). To neutralize ROS, the body employs enzymatic and non-enzymatic defense systems. The dietary intake of bioactive phenols, such as quercetin (Que), is a non-enzymatic system that can quench ROS and protect from pro-oxidative damage. In this review, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its antioxidant properties. Que not only acts as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups, but it can effectively inhibit the activity of several endogenous oxidative enzymes, binding them with high affinity and specificity. Among all targets, Que showed the best results in molecular docking simulations with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Taken together, these findings highlight the potential of Que as a natural antioxidant therapy for oxidative stress-related diseases.

A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds like nucleobases, sugars or peptides principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments, the latter offering preferential starting conditions for a subsequent RNA world.

Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of polysaccharides from Codium fragile (PCF) on prebiotic and anti-obesity activity. PCF increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with PCF as carbon source were higher than for the glucose as control. Moreover, PCF inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that PCF can be used as prebiotic material with anti-obesity for human health.

It is proposed that the primary living cells (“probionts”) cannot emerge of organic substance simply by continuous chemical complication of prebiotic macromolecules and microsystems. The complication must be accompanied by the radical thermodynamic transformation (“jump”) of prebiotic microsystems that resulted in the acquired ability to extract free energy from the environment and export entropy. This transformation is called “the thermodynamic inversion” The inversion may occur by means of the efficient (intensified) response of the microsystems on the oscillations of physic-chemical parameters in hydrothermal environment. In this case the surplus available free energy within a microsystem, when combined with the informational modality, facilitates its conversion into a new microsystem—a living probiont. It is shown the schematic representation of an oscillating prebiotic microsystem that is transforming into a living probiont. A new kind of laboratory and computational experiments on prebiotic chemistry under oscillating conditions is offered to verify the inversion concept.

Geochemists disagree whether or not prebiotic chemistry has existed already during the Hadean Eon and whether the then terrestrial atmosphere has been strongly or weakly reduced. Here I argue that cellular life has existed already just after the end of the Hadean Eon and that terrestrial life has survived a number of cataclysms during the Earth's history. I argue that although organic molecules have been detected in meteorites that most organic molecules required for the formation of macromolecules must have been formed on Earth. Finally, I argue that the primitive terrestrial atmosphere during the Hadean Eon has been weakly reduced, so that amino acids and small nucleic acids could have been formed. I suggest that the first self-replicable macromolecules have been similar to viroids.

Prebiotic organic synthesis reactions catalyzed by Earth-abundant metal sulfides are key processes for understanding the evolution of biochemistry from inorganic molecules, yet the catalytic functions of sulfides have remained poorly explored in the context of the origins of life. Past studies on prebiotic chemistry have mostly focused on a few types of metal sulfide catalysts, such as FeS or NiS, which form limited types of products with inferior activity and selectivity. To explore the potential of metal sulfides on catalyzing prebiotic chemical reactions, here, the chemical diversity (variations in chemical composition and phase structure) of 304 natural metal sulfide minerals in a mineralogy database was surveyed and approaches to rationally predict the catalytic functions of metal sulfides are discussed based on advanced theories and analytical tools of electrocatalysis such as proton-coupled electron transfer, structural comparisons between enzymes and minerals, and in-situ spectroscopy. To this end, we introduce a model of geo-electrochemistry driven prebiotic synthesis for chemical evolution, as it helps us to predict kinetics and selectivity of targeted prebiotic chemistry under “chemically messy conditions”. We expect that combining the data-mining of mineral databases with experimental methods and theories developed in the field of electrocatalysis will facilitate the prediction and verification of catalytic performance under a wide range of pH and Eh conditions, and aid in the rational screening of mineral catalysts involved in the origins of life.

We report a prebiotically relevant solution to the N1-ribosylation of pyrimidine nucleobases, a well-known challenge in the RNA World hypothesis. It is found that the presence of metal cations and clay mineral enables the previously unachievable direct ribosylation of uracil, providing by far the highest yield. Spectroscopy and chromatography analyses confirmed the formation of ribosylated uracil. The method can also be extended to the ribosylation of 2-pyrimidinone. These findings are also compatible with the metal-doped-clay model developed by our lab for the unified route of the selection of ribose and subsequent syntheses of nucleotide and RNA.

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Herein, we developed a novel method for the synthesis of uniformly sized microparticles via coaxial flow-phase separation. The study evaluated the effect of various process parameters on microparticle size and polydispersity including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution whereas surfactant concentration had the most substantial impact on the morphology of particles. Several microparticle formulations yielding particle sizes in the range of (5-50 µm), morphology, and concentration were synthesized as a demonstration of the tunability and scalability of this method. Notably, by controlling the process parameters microparticles of less than ~ 7 μm could be made using polymer concentrations varying by an order of magnitude. Finally, we demonstrated the tunability and scalability of this method by showing a 10-fold increase in encapsulation efficiency, a 3-fold increase in drug loading of a model hydrophilic drug, and modified release kinetics in microparticle formulations of comparable sizes but different polymer concentrations.

Nanotechnology has become a popular topic in agricultural and animal research, generating sig-nificant global interest. Nanoparticles (NPs)-enabled agriculture and animal husbandry (AHs) products have three main principles: crop production, protection, and nutrient enrichment. Re-search on this topic has grown exponentially in recent years, with an increasing number of peer-reviewed literature and patents on NPs-enabled agriculture and AH products. This study examines and collects data on the various applications of NPs-enabled agricultural products for crop production, protection, and livestock improvement from the core nanotechnological database. The search returned several types of NPs and products used in agriculture and AH, countries that utilize these products at a commercial level, and analysis of these data by phyton, R-statistical software. Our findings show remarkable growth of nanotechnology in agriculture, AH, and re-search fields for future sustainability goals in the era of climate change

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples (p<0.03). Oatwell’s effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h: 0.67 OTUs; 24 h: 5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Nurses have experienced several psychological and work-related issues during the COVID-19 pandemic including pandemic burnout and job burnout. The aim of the study was to examine the impact of social support and resilience on COVID-19 pandemic burnout and job burnout among nurses. We conducted a cross-sectional study in Greece. Study population included 963 nurses. We measured social support, resilience, COVID-19 pandemic burnout, and job burnout with the Multidimensional Scale of Perceived Social Support, Brief Resilience Scale, COVID-19 burnout scale, and single item burnout measure respectively. Nurses received high levels of social support, while their resilience was moderate. Additionally, nurses experienced moderate levels of COVID-19 burnout and job burnout. Increased social support (adjusted beta = -0.075, 95% CI = -0.125 to -0.024) and increased resilience (adjusted beta = -0.399, 95% CI = -0.491 to -0.308) were associated with reduced COVID-19 pandemic burnout. We found a negative relationship between social support and job burnout (adjusted beta = -0.263, 95% CI = -0.405 to -0.121). A similar negative relationship was found between resilience and job burnout (adjusted beta = -0.529, 95% CI = -0.785 to -0.272). Social support and resilience can act as protective factors against COVID-19 pandemic burnout and job burnout among nurses. Policy makers should develop and implement appropriate strategies to improve nurses’ social support and resilience since they are the backbone of healthcare systems worldwide.

The origin of life was a cosmic event happened on primitive Earth. A critical problem to better understand the origins of life in Earth is to glimpse in which chemical scenarios the basic building blocks of biological molecules could be produced. Classic works in pre-biotic chemistry frequently considered early Earth as a homogeneous atmosphere constituted by chemical elements such as methane (CH₄), ammonia (NH₃), water (H₂O), hydrogen (H₂) and hydrogen sulfide (H₂S). Under that scenario, Stanley Miller was capable to produce amino acids and solved the question about the origin of proteins. Conversely, the origin of nucleic acids has tricked scientists for decades as nucleotides are complex though necessary molecules to allow the existence of life. Here we review possible chemical scenarios that allowed not only the formation of nucleotides but also other significant biomolecules. We aim to provide a theoretical solution for the origin of biomolecules at specific sites named “Prebiotic Chemical Refugia”. A prebiotic chemical refugium should therefore be understood as a geographic site in prebiotic Earth on which certain chemical elements were accumulated in higher proportion than expected, facilitating the production of basic biomolecules. Plus, this higher proportion should not be understood as static, but dynamic; once the physicochemical conditions of our planet changed periodically. This different concentration of elements, together with geochemical and astronomical changes along days, synodic months and years provided somewhat periodic changes in temperature, pressure, electromagnetic fields, and conditions of humidity; among other features. Recent and classic works suggesting most likely prebiotic refugia on which the main building blocks of biological molecules might be accumulated are reviewed and discussed.

This review considers the generation of relatively simple biomolecules, e.g., primary amino acids, resulting from the rapid collapse of bubbles in aqueous solutions containing various, low molar mass, gases. Some of the possible primary reactions occurring to produce the biomolecules are introduced and discussed. A brief discussion is included on the possible involvement of hydrodynamic cavitation, at the primordial seashore, as the initiating processes for the formation of the first organic molecules on prebiotic earth and the origins of life on Earth some 4 billion years ago.

Phylogenomics has enriched our understanding that the Tree of Life can have network-like or reticulate structures among some taxa and genes. Non-vertical modes of evolution—such as hybridization/introgression and horizontal gene transfer—deviate from a strictly bifurcating tree model, causing non-treelike patterns. Here, we present a brief overview of a phylogenomic workflow for inferring organismal histories and compare methods for detecting reticulate evolution. We discuss how the timing of coalescent events can help disentangle introgression from incomplete lineage sorting and how horizontal gene transfer events can help determine the relative timing of speciation events. In doing so, we identify pitfalls of certain methods and discuss how to extend their utility across the Tree of Life. Workflows, methods, and future directions discussed herein underscore the need to embrace reticulate evolutionary patterns for understanding the timing and rates of evolutionary events, providing a clearer understanding of life’s history.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

As the digital era advances, many industries continue to expand their use of digital technologies to support company operations, notably at the customer interface, bringing new commercial opportunities and increased efficiencies. However, there are new sets of responsibilities associated with the deployment of these technologies, encompassed within the emerging concept of corporate digital responsibility (CDR), which to date has received little attention in the academic literature. This exploratory paper thus looks to make a small contribution to addressing this gap in the literature. The paper adopts a qualitative, inductive research method, employing an initial scoping literature review followed by two case studies. Based on the research findings, a simple model of CDR parameters is put forward, and the article concludes with a discussion of a number of emergent issues - fair and equitable access, personal and social well-being, environmental implications, and cross-supply chain complexities - that suggest possible directions for future research.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of homochiral and heterochiral peptides, a variety of computational methods were employed. 10 prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple previous meteorite, spark discharge, and hydrothermal vent studies. We focused on what had been reported as primary early Earth polypeptide analogs: 1ARK, 1PPT, 1ZFI, and 2LZE. Tripeptide composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in minimal folding energy of peptides, while the classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed 10 prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Prebiotic polypeptides were built up to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. Most interestingly, among 129 residues, mutation sensitivity profiles presented that the ratio of more stable to less stable to equally stable D-amino acids was about 1:1:1. In conclusion, some combinations of a mixture of L- and D-amino acids can act as essential building blocks of life. Peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets.

Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supplemented with HFD, XOS prevented hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. 1H-NMR analysis of caecal metabolites showed that compared to HFD, LFD group had healthier caecal short-chain fatty acid profile and the combination of HFD and XOS was associated with reduced caecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Caecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, our study identifies F. prausnitzii as a possible target to treat NAFLD with XOS. The underlying preventive mechanisms involved improved hepatic oxidative metabolism.

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

This article explores the intricate relationship between Human-Data Interaction (HDI) and Data Virtualization (DV), two integral fields that are redefining how we engage with and manage data in the digital age. Positioned at the intersection of technology and user-centric design, this study examines how DV can transcend traditional data management boundaries to significantly enhance data accessibility, legibility, and agency, thus fostering more ethical and meaningful interactions across various sectors. Opening with a detailed exposition on the evolving role of HDI, the paper contextualizes the importance of user-centric data practices within contemporary digital challenges. HDI’s principles are pivotal as they advocate for user empowerment in data interactions, ensuring that data processes are not only transparent but also negotiable and aligned with users’ needs and ethical standards. DV emerges as a transformative solution that inherently supports these principles by integrating diverse data sources into a cohesive and accessible format, thereby eliminating many of the inefficiencies found in conventional data management systems. Through a series of nuanced case studies, the paper provides empirical evidence of DV’s effectiveness across diverse domains. In healthcare, DV facilitates a holistic approach to patient care by providing seamless access to comprehensive medical records, thereby enabling faster, more accurate diagnostic and treatment processes. In the financial sector, DV proves instrumental in enhancing the detection and management of fraud, integrating transactional data across global platforms in real-time to allow for swift, proactive interventions. In education, DV supports personalized learning by synchronizing data from various educational tools, thus allowing for tailored educational experiences that respond dynamically to student performance and engagement metrics. Moreover, the paper critically addresses the ethical considerations and privacy concerns that arise with the integration of HDI and DV, particularly as data interactions become more pervasive and complex. By proposing forward-thinking research directions, it seeks to refine these technologies to better serve societal needs while addressing potential risks and governance issues. In conclusion, this study significantly contributes to the discourse on HDI by advocating for DV as an essential, innovative tool that enhances the clarity, fairness, and efficacy of data interactions. By demonstrating how DV can transform large-scale data sets into user-friendly formats that support decision-making and improve operational efficiencies, the paper underscores DV’s potential to advance a range of industries and enhance the daily lives of individuals interacting with digital systems.

Data collection and analysis are becoming more and more important in a variety of application domains as long as the novel technologies advance. At the same time, we are experiencing a growing need for human-machine interaction with expert systems pushing research through new knowledge representation models and interaction paradigms. In particular, in the last years eHealth - that indicates all the health-care practices supported by electronic elaboration and remote communications - calls for the availability of smart environment and big computational resources. The aim of this paper is to introduce the HOLMeS (Health On-Line Medical Suggestions) framework. The introduced system proposes to change the eHealth paradigm where a trained machine learning algorithm, deployed on a cluster-computing environment, provides medical suggestion via both chat-bot and web-app modules. The chat-bot, based on deep learning approaches, is able to overcome the limitation of biased interaction between users and software, exhibiting a human-like behavior. Results demonstrate the effectiveness of the machine learning algorithms showing 74.65% of Area Under ROC Curve (AUC) when first-level features are used to assess the occurrence of different prevention pathways. When disease-specific features are added, HOLMeS shows 86.78% of AUC achieving a more specific prevention pathway evaluation.

Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy, characterized by ventricular chamber dilatation and systolic dysfunction, in the absence of coronary artery disease, arterial hypertension, valvular or congenital diseases. DCM is a heterogeneous group of disorders of the myocardium caused by genetic factors, environmental factors, or a combination of both. DCM affects mainly men aged between 20 and 50 years, being considered one of the main causes of heart failure (HF) and the main indication for heart transplantation. Guideline-based HF treatment is the mainstay of management for patients with DCM. In recent years, gene therapy and induced pluripotent stem cells have become promising strategies. In this review, we summarize the relevant clinical issues, and current treatment of DCM patients, including the role of genetic evaluation.

The Anthropocene has created a new cartography where various discursive levels are intertwined. It unites two fields of knowledge: geology and anthropology. In the 19th century, Romanticism challenged the separation between natural sciences and spirit sciences. With the Anthropocene a geological era is established, but with an epistemological dimension: environmental catastrophes are not a passive "object", they become an agent of social and political change. Images of the world (Weltbild) turn nature into an animated whole that challenges the dual vision: observer and observed. There is no nature without "observer", nor geology without anthropology. The Anthropocene modifies the foundations of our view of the world where we had excluded life. This is how concepts such as symbiogenesis, homeostasis, etc., which make visible and try to explain phenomena that are otherwise inexplicable. The Naturwissenschaft by J.W. Goethe is a point of support, with all these ideas that develop in the 20th century and anticipate the Anthropocene term of the 21th century. While the concepts of "belief" and "science" continue to be sharpened, rehabilitating "old quarrels" around anthropology, cosmology, theology, etc. The dignity of man is at stake.

The remarkable success of taxonomic discovery, powered by culturomics, genomics and metagenomics, creates a pressing need for new bacterial names, while holding a mirror up to the slow pace of change in bacterial nomenclature. Here, I take a fresh look at bacterial nomenclature, exploring how we might create a system fit for the age of genomics, playing to the strengths of current practice, while minimising difficulties. Adoption of linguistic pragmatism, obeying the rules while treating recommendations as merely optional will make it easier to create names derived from descriptions, from people or places or even arbitrarily. Simpler protologues and a relaxed approach to recommendations will also remove much of the need for expert linguistic quality control. Automated computer-based approaches will allow names to be created en masse before they are needed, while also relieving microbiologists of the need for competence in Latin. The result will be a system that is accessible, inclusive and digital, while also fully capable of naming the unnamed millions of bacteria.

In the digital era in which over 4 billion people regularly access the internet, the conventional process of publishing scientific articles in academic journals following peer review is undergoing profound changes. Following physics and mathematics scholars who started to publish their work on the freely accessible arXiv server in the early 1990s, researchers of all disciplines increasingly publish scientific articles in the form of freely accessible and fully citeable preprints before or in parallel to conventional submission to academic journals for peer review. The full transition to open science, I argue in this study, requires to expand the education of students and young researchers to include scholarly communication in the digital era.

The goal of germplasm enhancement is to introgress traits from wild crop relatives into cultivated material and eventually cultivars. It seeks to restore genetic diversity that has been lost over time or to augment cultivated material with novel alleles that improve parents in breeding programs. This paper discusses potato germplasm enhancement efforts in the past, focusing on effective examples such as disease resistance and processing quality. In addition, it outlines new strategies for enhancement efforts, shifting the focus from evaluating phenotypes to tracking and manipulating specific DNA sequences. In the genomics era, germplasm enhancement will increasingly be focused on identifying and introgressing alleles rather than traits. Alleles will come from a broad pool of genetic resources that includes wild species relatives of potato, landraces, cultivated potato itself, and distantly related species. Genomics tools will greatly increase the efficiency of introgressing multigenic traits, and will make it possible to identify rare alleles and utilize recessive alleles.

ABSTRACT Education is the most important instrument in human life because education can increase human dignity. In addition, education can also be a benchmark for human quality and an example of the progress of a nation. The history of education in Indonesia has evolved from the colonial era to the digital era. These developments have influenced government policies in every era. In the 21st century, the development of education in Indonesia is starting to show progress. This is because it is supported by the rapid growth of information and technology. This research article aims to analyze the educational policies carried out by the government from the colonial era to the digital era to be used as evaluation material at this time so that in the future education in Indonesia is even better. To achieve this goal, this research focuses on the question of how is the transformation of education in Indonesia from the colonial era to the digital era? and what is the paradigm of education in Indonesia when viewed from a historical perspective?. The research method used is the Literature Review method from 27 sources in journal articles, websites, and data reports for 2019-2021. The results of this study found that changes in the Indonesian education system from time to time have a positive influence on the progress of the Indonesian nation. The development of education in Indonesia also has an impact on increasing the Human Development Index (HDI). This shows that the quality of Indonesian society is increasing. Based on the results obtained, it is hoped that it can provide information about the transformation of education in Indonesia from the colonial era to the digital era from a historical perspective. This article is suitable as a reference source for education observers in Indonesia to know the history of education and its policies from the colonial era to the digital era and useful for academics to know the history of education in Indonesia. This research has limitations, namely this research is only limited to the development of education in Indonesia from the colonial era to the digital era and the paradigm of education development in Indonesia from a historical perspective.

This paper analyzes the main variables which determines the relation between disinformation and the youth responsibility during the last stage of Covid-19 pandemic in Spain. The document presents relevant results on this subject. At the Introduction the reader will find the theoretical framework of the following concepts: disinformation, responsibility, credibility, and youth responsibility variables. The greatest interest, considering the authors specialization, falls in communication factors. The methods applied had been the reference review of the literature found about this subject, as well as a qualitative opinion research through discussion groups with young University students from Communication Schools in Madrid, both public and private. This recent study, held in June 2021, provide a very rich material for this paper. The main results and findings are the facts of being not satisfied with the information received about Covid-19; the knowledge about their most credible sources; the connection between information and responsibility, and some of the solutions said by youth to be more responsible in this context. As a conclusion, this paper confirms the first hypothesis of considering the disinformation as a variable which causes the lack of youth responsibility. Regarding the second hypothesis it is checked that young people consider communication as a solution for being more responsible.

The antibiotic or antimicrobial resistance is rapidly spreading in microbes relevant to human health. Two visible major contributory factors have been the indiscriminate overuse of antimicrobials for preventing diseases in human and to enhance the productivity in agriculture sector. To mitigate the potential threat posed by post-antibiotic era, the global health stakeholders have been making extra efforts at a war footing to formulate and implement global and national plans of action. In the current article, an endeavour is made to provide a perspective to look beyond the current focus on just use of the antimicrobials. Attention has been drawn towards various obvious and not-so-obvious self-preservation infection-prevention practices in vogue from the pre-antibiotic era whose usage has been on decline in the antibiotic era for various reasons. Particularly, the practices with a clear potential to effectively decrease the spread of pathogens through contact, curtail the evolution and dissemination of the antimicrobial resistance in local environment and its introduction into the global community, should be Identified and strengthened to make them part of comprehensive hygiene and quarantine practices. Broadly, the suggestions pertaining to the personal and community hygiene including bereavement practices, isolation and quarantine of suspected pathogen carriers, and water and environment security have been made to invoke a constructive debate and discussion among various stakeholders for their evaluation and implementation to effectively delay the development of antimicrobial resistance wherever possible and disrupt its spread to pathogens.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

Flares, sometimes accompanied by coronal mass ejections (CMEs), are the result of sudden changes in the magnetic field of stars with high energy release through magnetic reconnection, which can be observed across a wide range of the electromagnetic spectrum from radio waves to the optical range to X-rays. In our review, we attempt to collect some fundamental new results, which can largely be linked to the Big data era that has arrived due to the expansion of space photometric observations of the last two decades. We list the different types of stars showing flare activity, their observation strategies, and discuss how their main stellar properties relate to the characteristics of the flares (or even CMEs) they emit. Our goal is to focus, without claiming to be complete, on those results that may in one way or another challenge the "standard" flare model based on the solar paradigm.

Emerging infectious diseases (EIDs) continue to be a problem all across the world, but in certain areas the threat is greater than in others. The detection of new diseases will aid in the focus of surveillance efforts. Specifically, identifying a "patient zero" is critical step to help limit further transmission. In fact, several factors have been found to contribute to emerging infectious diseases emergence and transmission. Antigenic drift is an important factor that affects vaccine effectiveness and it is important for scientists and healthcare providers alike to understand how this process works in order to ensure that people receive effective vaccinations against infectious diseases. However, recent advances in biotechnology, immunology and artificial intelligence have enabled us to make progress in diagnosis, treatment, prevention and control of infectious diseases. The fight against infectious diseases will always be ongoing, but the advancement of bioscience offers a promising outlook for the near future. In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a large number of known and unknown viruses, many of which could spillover into animal and human populations. In this article, we discuss the potential risk factors that contribute in emerging infectious diseases. Also, we discuss the management of disease prevention and control.

In this work we present a new algorithm that achieves the perfect Shannon secret by means of the XOR function and a method that we call multiple key reuse. The algorithm has two execution modes: message authentication and data encryption. The XOR encryption scheme allows for batch encryption and exhibits Perfect Forward Secrecy (PFS). Furthermore, based on our fundamental algorithm, we have developed a new strategy for blockchain implementation that does not require Proof of Work (PoW), but defines a fair mechanism for miner selection and secure addition of blocks to the chain. Since our method is mainly based on the Boolean XOR function, the strength of the cryptosystem can be directly established thanks to its mathematical properties. Due to the risk that quantum computers represent for current cryptosystems based on prime factorization or discrete logarithm, we postulate that our method represents a promising alternative in the quantum era for the security of communications between Internet of Things devices as well as Blockchain technology.

In this COVID-19 pandemic, the use and dependency on Internet has grown exponentially. The number of people doing online activities such as e-learning, remote working, online shopping and others have increased. This has also led to increased vulnerability to cyber crimes. Cyber security attacks have become a serious problem. The common types of cyber security attacks are phishing, malware, ransomware, social engineering, identity theft and denial-of-service. The attackers target the victims in order to get their credential information or financial benefits. Those people who are doing online activities are vulnerable to cyber threats. This is because the network is not safe. The attackers are able to code according to the weaknesses of the Internet. Once the attackers hack into the devices, they have the root access and can do whatever they want to do with the device. In this research paper, the concept of cyber security attack and detailed research about real attacks are discussed. This is followed by detailed review about the recent cyber security attacks with a critical analysis. Moreover, the research paper will be proposing the latest research contribution of cyber security during COVID-19 and the implementation scenario which will give the examples about how the companies maintain privacy as well as the limitations. Then, the paper will be discussing the reasons that people are vulnerable to cyber security and the unique solution to the problems stated. Finally, this paper will conclude with an in-depth analysis and future direction for cyber security research.

The current Covid-19 pandemic has hugely disrupted the delivery of routine and established medical care. Patients can develop a wide range of clinical signs and symptoms from a cough and fever to severe respiratory failure. There is an ongoing argument on a concise investigative pathway to ensure the safety of all healthcare workers. The stethoscope can help with any clinical respiratory assessment but the risk of cross infection is high. Computer tomography should not be routinely performed. There is a potential place for lung ultrasound but outcomes are not yet determined.

Fibre-based dietary interventions are at the forefront of gut microbiome modulation research, with a wealth of 16S rRNA information to demonstrate the prebiotic effects of isolated fibres. However, there is a distinct lack of data relating to the effect of a combination of soluble and insoluble fibres in a convenient to consume fruit juice food matrix on gut microbiota structure, diversity, and function. Here, we aimed to determine the impact of the MOJU Prebiotic Shot, a fruit juice drink blend containing chicory inulin, baobab, golden kiwi, and green banana powders, on gut microbiota structure and function. Healthy adults (n = 20) were included in a randomized, double-blind, placebo-controlled, cross-over study receiving 60ml MOJU Prebiotic Shot or pla-cebo (without the fibre mix) for 3 weeks with a 3-week wash-out between interventions. Shotgun metagenomics revealed significant between-group differences in alpha and beta diversity. In addition, the relative abundance of the phyla Actinobacteria and Desulfobacteria was significantly increased as a result of the prebiotic intervention. 9 species were observed to be differentially abundant (uncorrected p-value of <0.05) as a result of the prebiotic treatment. Of these, Bifidobacterium adolescentis and CAG-81 sp900066785 (Lachnospiraceae) were present at increased abundance relative to baseline. Additionally, KEGG analysis showed an increased abundance in pathways associated with arginine biosynthesis and phenylacetate degradation during the prebiotic treatment. Our results show the effects of the daily consumption of 60ml MOJU Prebiotic Shot for 3 weeks and provide insight to the functional potential of B. adolescentis

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

Although learning analytics (LA) holds great potential to improve teaching and learning, LA research and practice are currently riddled with limitations that impact every stage of the LA life cycle. The present paper offers an overview of these challenges before proposing strategies to overcome them and exploring how the recent innovations brought forth by language models can improve LA research and practice. In particular, we encourage the empowerment of teachers during LA development, as this would strengthen the theoretical foundation of LA solutions and increase their interpretability and usability. Furthermore, we provide examples of how process data can be used to understand learning processes and generate more interpretable LA insights. Furthermore, we explore how LLMs could come into play in LA to generate interpretable insights, timely and actionable feedback, increase personalization, and support teachers’ tasks more broadly.

This paper reviews the low-resilience problem in many cities, poor designs of cities to cope with disasters, and the need for tolerance of urban constructions. It explores answers concerning the question of how shall we build cities resiliently? The method of this applied research is a multiphase process that considers all physical and socioeconomic elements of a city. It introduces six indicator groups of urban management (M), economy (E), built environments (U), Infrastructures (I), natural environments (N), and health protection (H). The groups include 55 indicators as variables in the mathematical calculations in this paper. This paper builds a mathematical model to maximize the profitability of resilient buildings by optimizing investments in the required projects. The projects will upgrade the firmness and tolerance of cities against nature-based and human-made dangers and risks. There is a linear programming in 55 variables to select optimal solutions from fifty-five factorial alternatives. Then, the programming will develop into non-linear programming. The unique innovation of this paper is its linear programming interpretation by non-linear to give optimal solutions for the problem. Applying the Lagrange function in the Kuhn-Tucker conditions proves the accuracy of the hypothesis that post-COVID urbanization requires maximum resilience. Only in this way, the urban economies will be free of risks. Outcomes in this paper will assist in the pre-planning, design, and building of built environments everywhere resilient and sustainable.

Pancasila is the identity of the Indonesian nation, which means that Pancasila is a national characteristic that cannot be found in any country. Pancasila points are taken from the noble values of the Indonesian state. These principles contain culture, customs, and national character known as manners, cooperation, and high nationalism. As the successor to Indonesian culture, the young generation must be able to preserve and develop Pancasila. In this era of globalization, there are many challenges for the younger generation in preserving Pancasila. This study aims to provide an overview of the decline of Pancasila identity among the younger generation due to the impact of globalization. The research question that has been determined is how the practice behaviour of the younger generation towards the implementation of Pancasila, the solutions and efforts that all Indonesian people can make regarding the crisis of Pancasila identity in the era of globalization. This research method uses a literature review. The research sources were conducted from the latest journals and books published in 2019 until 2021 related to the theme of Pancasila and the millennial generation. The results showed that globalization has greatly facilitated foreign cultures to enter Indonesia. The younger generations use this foreign culture as a lifestyle without filtering it, whether it contains Pancasila values or not. This causes Pancasila has been forgotten and no longer applied in their everyday life. Young people can make various efforts to preserve the national identity, namely Pancasila. Apart from the role of the young generation itself, Indonesian society can also play an essential role in supporting the younger generation to continue implementing Pancasila in their lives. By conducting this research, it is hoped that Indonesia's young generation can understand, select, and stay away from the negative impacts of globalization that enter Indonesia freely. The solution that can be given from this research is that the younger generation must love their own culture more and practice every principle in Pancasila. Parents, educational institutions, and the government must also support the younger generation to maintain national identity, Pancasila values. The limitation of this research is that the researcher did not conduct any primary data, which means the data were not directly from the source. This causes the accuracy of this study to be less guaranteed. The recommendation that the researchers can give for further research is to obtain primary data to ensure accuracy and explore research topics regarding the fading of Pancasila identity in the younger generation in this era of globalization.

In most world’s countries, scholarship evaluation for tenure and promotion continues to rely on conventional criteria of publications in journals of high impact factor and grant funding. Continuing to hire and promote scholars for their achievements in research and in securing research funds exposes universities at risk because students, directly and indirectly through government funds, are the main source of revenues for academic institutions, whereas talented young researchers are those who actually carry out most of the published research. Purposeful scholarship evaluation needs to include all three areas of scholarly activity: research, teaching and mentoring, and service to society. Young scholars seeking tenure and promotion benefit from the practice of open science because it provides better and more impactful results with respect to each of the three areas of scholarship.

Smartphone has become one of the most revolutionary devices in the history of computing. With various kinds of applications, the scope of smartphone has been significantly broadened in the past few years including almost every aspect in our daily life. However, due to the limited on-board resources such as CPU, storage, network bandwidth and battery power, smartphones and the mobile network serving them bring new challenges that have not been encountered in the traditional computing and networking environments. This dissertation focuses on the research areas of improving the network architecture and enhancing the current applications on smartphones. It mainly investigates the areas in the following two directions for three representative categories of mobile services. - In the first direction, the dissertation aims to develop new communication models for smartphone Ad-Hoc networks to achieve efficient communication in the proximity. It is motivated by the fact that smartphone Ad-Hoc networks can help improve the current location-based services and propel new applications. Moreover, the new communication models provide complementary alternatives to the traditional infrastructure-based wireless networks. - In the second direction, the dissertation focuses on improving the other two categories of services, cloud storage services and real-time video streaming services for mobile devices. In the field of cloud storage, we introduce a cloud-assisted approach to provide a set of advanced file operations, such as encryption, decryption and compression, on smartphones. Furthermore, by utilizing the on-board Near Field Communication(NFC) module, we develop an algorithm to securely share the files between mobile devices. For the services of real-time video streaming, we propose approaches that identify a user’s status by analyzing the accelerometer data and then, dynamically adjust the buffer mechanism to save network bandwidth on smartphones.

The worldwide interconnected objects, called Internet of Things (IoTs), have been increasingly growing in the last several years. Different social media platforms and devices are continuously generating data about individuals and facilitate the technological and the social convergence of their Internet-based data and services with globalized users. These social and device-related IoTs create rooms for data breaches as such platforms provide ability to collect private and sensitive data. We assert that data breaches are fundamentally failures of access control - most users are too busy or technically ill-equipped to understand access control policy expressions and decisions. We argue that this is symptomatic of globalised societies structured by the conditions of algorithmic modernity; an era in which our data is increasingly interdependent on, and enmeshed with, ever more complex systems and processes that are vulnerable to attack. Ethically managing data breaches is now too complex for current access control systems, such as Role-Based Access Control (RBAC) and Context-Aware Access Control (CAAC). These systems do not provide an explicit mechanism to engage in decision making processes, about who should have access to what data and when, that are involved in data breaches. We argue that a policy ontology will contribute towards the development of Ethical CAAC better suited to attributing accountability for data breaches in the context of algorithmic modernity. We interrogate our proposed Ethical CAAC as a theoretical construct with implications for future policy ontology models and data breach countermeasures. An experimental study on the performance of the proposed framework is carried out with respect to a more generic CAAC framework.

The rapid development of quantum computing devices promises powerful machines with capabilities that solve a wide range of problems that traditional computers cannot. Therefore, quantum computers generate new threats at unprecedented speed and scale and specifically pose an enormous threat to encryption. Lattice-based cryptography is considered to be the rival to a quantum computer attack and the future of post-quantum cryptography. So, cryptographic protocols based on lattices have a variety of benefits, like security, efficiency, lower energy consumption, and speed. In this work, we study the most well-known lattice-based cryptosystems while a systematic evaluation and comparison is presented also, and focuses on their strengths and weaknesses.

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital and probably appeared during biogenesis four billion years ago. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and protein molecules, drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: tRNAs, aaRS, mRNAs, and ribosomes. When assembled in the right order, the translation machine created biosynthetic polypeptides, a process that transferred information from mRNAs to proteins. This was the beginning of the prebiotic information age. The molecular attraction between tRNA and amino acids led to different stages of the translation machines and the genetic code. tRNA is an ancient molecule that designed and built mRNA for storing the information of its cognate amino acid. Each mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional. The origin of the genetic code is enigmatic; herein we propose an evolutionary explanation: the demand for a wide range of specific enzymes in the peptide/RNA world was the main selective pressure for the origin of information-directed protein synthesis. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the adaptive theory. These three theories are compatible with our coevolution model of the translation machines and the genetic code. We suggest biosynthetic pathways as the origin of the specific translation machines which provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machines: GNC code developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to understand the prebiotic information system better, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the translation might have worked in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. Using AnyLogic software we were able to simulate and visualize the entire evolution of the translation machines and the genetic code. The results indicate that the emergence of the information age from the peptide/RNA world was a watershed event in the origin of life about four billion years ago.

The Genotype-Phenotype Working Group was established in November 2021 as part of the AgBioData Consortium (https://www.agbiodata.org) with the goal of identifying current challenges in annotating and integrating large-scale genotype and phenotype data. Over the course of the year, the members of this working group identified different types of data sets, explored experimental platforms and methods for data generation, and examined how these data are annotated including the metadata requirements. We conducted a thorough review of publicly funded repositories for raw and processed data for each data type. We also examined several secondary databases and knowledgebases that enable the integration of heterogeneous data types in the context of the Genome Browser, Pathway Networks and tissue-specific gene expression. The review revealed a need for additional infrastructural support, standards, and tools to connect Genotype to Phenotype data and enhance data interoperability for knowledge synthesis and to foster translational research.

Innovation has emerged as a critical driver of economic growth in the digital era, revolutionizing industries and reshaping economies worldwide. As traditional funding avenues continue to be dominated by risk-averse lenders and investors, entrepreneurs are increasingly turning to alternative funding mechanisms to fuel their innovative ideas and ventures. This article delves into the evolving landscape of financing innovation in the digital era, with a primary focus on the role of alternative funding mechanisms. By drawing on a comprehensive review of existing literature and empirical evidence, we aim to provide a conceptual framework that elucidates the interplay between alternative finance platforms, innovation ecosystems, and entrepreneurial activities. Moreover, this article examines the unique characteristics and challenges associated with financing innovation through crowdfunding, venture capital, and angel investing. The insights from this research contribute to a better understanding of how these alternative funding mechanisms can effectively support and catalyze innovation across industries and economies.

The fourth industrial revolution has resulted in the digitalization of projects and operations across all sectors. Accordingly, efforts are being made to utilize advanced technologies to improve the energy efficiency of the building sector. This study has reviewed the current application and limitations of cutting-edge technologies in this regard. An overview of the use of the Internet of Things (IoT), artificial intelligence (AI), digital twin (DT), and building information modeling (BIM) for energy efficiency of buildings has been provided. It has been found that the use of Industry 4.0 technologies, during the construction and operational phase of buildings, has a great potential to reduce energy consumption and emissions of the sector. This study may help stakeholders of the built environment to understand the role of industry 4.0 tools for energy efficiency of the sector.

This article examines how digitalisation is impacting the management of IT. Phase 1 of the re-search focuses on the German automotive industry, and adopts a qualitative inductive approach, based on feedback from 19 semi-structured interviews with IT managers and professionals. Five key aspects of digitalisation are identified, and a new model for the management of IT is devel-oped. Phase 2 then reviews the deployment of digital technologies in eight organisations from other industry sectors and assesses the overall impact on the management of IT. The results suggest that the transition to new IT management structures in the German automotive industry may be the forerunner of a change process that will impact more widely in other industries, in particular where digital technologies are now embedded in an organisation’s products or services. The results also provide some new perspectives on the conceptualisation of digitalisation and digital transformation, and represent a contribution to the developing theory around new tech-nology deployment and IT management in the digital era.

Technology Readiness Levels (TRLs) is a well-established and widely used approach for defining the readiness of new technology. To this extent, it assesses technology maturity against specific benchmarks, ranging from 1 (concept) to 9 (market solution). Although this is a useful classification service, allowing us to establish a common language, there are cases where we find that this conceptual approach fails to adequately highlight the maturity of certain innovative endeavors and effectively steer their development to higher TR levels. We will present an empirical case where the TRL approach presented a critical shortcoming in highlighting the true and effective readiness of a specific technological development and could not suggest the next natural step in ascending the maturity ladder. We will seek to generalize for the case of co-creation at large, analyze why co-creation may be poorly serviced by the current TRL model and suggest an amendment that would allow the observed shortcoming of the traditional TRL approach to be overcome and its use extended also in such co-creative settings.

The classical human satellite DNAs, also referred to as human satellites 1, 2 and 3 (HSat1, HSat2, HSat3, collectively HSat1-3) constitute the largest individual arrays of tandemly repeated DNA sequences in the genome. Even though they were among the first human DNA sequences to be isolated and characterized at the dawn of molecular biology, HSat1-3 have been left behind in the genomics era and remain among the most enigmatic sequences in the human genome. Although HSat1-3 total roughly 3% of the genome on average, they were almost entirely missing from the human genome reference assembly for 20 years. Recently, the Telomere-to-Telomere Consortium produced the first truly complete assembly of a human genome, including the enormous HSat1-3 arrays, opening them up for a new wave of discovery. Towards this end, here, I provide an account of the history and current understanding of HSat1-3 genomics, evolution, and roles in disease.

Introduction: Industrial revolution 4.0 in the current era of globalization plays an active role in the modern era in Indonesia. The influence of increasingly advanced technology affects the millennial generation as the nation's next generation to make Pancasila the basis of the State or the foundation of a State. In addition, the millennial generation has begun to shift the guidelines of life from Pancasila so that the appreciation of Pancasila values is starting to disappear along with the development of the times and in line with the progress of Science and Technology (IPTEK). If this continues, then the values of Pancasila will be replaced by a new ideology that will cause behavioural changes in society. Purpose: this study aims to provide the proper application to millennial life using Pancasila values, knowing the behaviour of the millennial generation towards the implementation of Pancasila values, and making Pancasila a way of life. Methods: the method used in this research is Literature Review and takes sources from journals published in 2019 to 2021 related to the Pancasila theme and the millennial generation. Results: the study results show that with the existence of Pancasila as the ideology and principle of the State, it is expected to strengthen the attitude and nature of the community in accepting things outside the norms that exist in Indonesia. In addition, the younger generation is expected to be able to apply Pancasila values along with the development of science and technology in the modern era and current globalization. The research question is how to make the millennial generation implement Pancasila in life in the contemporary period and what solutions can continue to instil Pancasila values ​​in the 4.0 industrial revolution. Recommendation: the conclusion drawn is that Pancasila can become a unifying tool for the nation if the current generation or millennial generation still desires to maintain its values ​​, even though they are in a modern era and many influences from its outside cultures. Limitation: the limitation of this research is not getting all the data directly from the source. The researcher recommends using primary data for the following study to ensure its truth and accuracy better because the researcher directly obtains it.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

Carrot juice and its associated beverage products are well-known healthy drinks all over the world. However, what effect carrot juice has on the human gut microbiota and how it is fermented by the intestinal microbes have not been studied. Here, using an in vitro model of anaerobic fermentation, we demonstrated that carrot juice could be fermented into lactate and acetate by the human gut microbiota. 16S high-throughput sequencing and bioinformatic analyses indicated that fermentation of carrot juice could significantly change the composition of the human gut microbiome. Interestingly, carrot juice remarkably increased the abundances of beneficial bacteria, including Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus mucosae and Bacteroides uniformis and decreased the population of opportunistic pathogenic bacteria, such as Enterococcus faecium in the gut. Collectively, our study illustrates a favorable effect of carrot juice on the human gut microbiota and lays a foundation for the development of carrot juice as a novel prebiotic agent.

Brucellosis is one of the most common etiologies of laboratory-acquired infections worldwide, and handling of living brucellae should be performed in a Class II biological safety cabinet. The low infecting dose, multiple portals of entry to the body, the great variety of potentially contaminated specimens, and the unspecific clinical manifestations of human infections facilitate the unintentional transmission of brucellae to laboratory personnel. Work accidents such as spillage of culture media cause only a small minority of exposures, whereas >80% of events result from unfamiliarity with the phenotypic features of the genus, misidentification of isolates, and unsafe laboratory practices such as aerosolization of bacteria and working on an open bench without protective goggles or gloves. Although the bacteriological diagnosis of brucellae by traditional methods is simple, the Gram stain and the biochemical profile of the organism, as determined by commercial kits, can be misleading, resulting in inadvertent exposure and contagion. The use of novel identification technologies is not hazard-free. The MALDI-TOF technology requires an initial bacterial inactivation step, while the instruments’ reference database may misidentify Brucella as belonging to other Gram-negative species. The rapid identification by the FISH method mistakes brucellar isolates for members of the closely related Ochrobactrum genus.

Having sustained, over the course of more than two decades, record-breaking natural catastrophe losses, American insurers and reinsurers are justifiably questioning the potential linkage between anthropogenic climate change and extreme weather. Here, we explore issues pertaining to this linkage, looking at both the likely short-term implications for the insurance industry, as well as potential longer-term impacts on financial performance and corporate resilience. We begin our discussion with an overview of the implications that climate change is likely to have on the industry, especially as it relates to how catastrophic risks are construed, assessed, and managed. We then present the rudiments of an econometric analysis that explores the financial resilience of the property/casualty (P/C) industry in the face of both natural and man-made catastrophes. In this analysis, we explore the profitability consequences of several illustrative scenarios involving large-scale losses from extreme weather—specifically, a sequence of storms like those striking the U.S. in 2004—and a scenario that explores the prospect of a Katrina-scale storm in combination with a mass terror attack on the scale of 9/11. At systemic levels of aggregation, our analysis suggests a high degree of macro-resilience for the insurance industry. Moreover, we find that insurer resilience is higher for larger impacts, considering both the speed of recovery, as well as the inverse of the area under the unaffected system profile. We conclude with a summary of our findings and a closing commentary that explores the potential implications of these results for P/C insurers moving forward.

Delve into the ebb and flow of human ingenuity as the researcher traces the evolution of writing from papyrus to pixels. Discover how humble instruments like quill pens and typewriters have propelled human into the digital frontier, forever reshaping the art of expression in the modern age. This article examines the evolution of writing tools from traditional pen and paper to digital writing in the modern age. It explores the development of writing materials such as papyrus, parchment, and paper, as well as the invention of writing tools including quill pens, fountain pens, and typewriters. The rise of digital writing tools, including word processing software and smartphones, is also discussed, along with their benefits such as increased efficiency and productivity, enhanced collaboration and sharing capabilities, and greater accessibility and flexibility. However, the article also highlights the challenges of writing in the digital age, including the impact of digital distractions on writing focus and quality, the issue of online plagiarism and copyright infringement, and the potential loss of traditional writing skills. The article concludes with recommendations for educators, school administrators, students, and researchers to strike a balance between digital and traditional writing practices, to embrace digital writing tools while preserving traditional writing skills, and to understand the importance of the evolution of writing. The theoretical frameworks of Social Construction of Technology (SCOT) Theory, Media Ecology Theory, and Activity Theory are also discussed in relation to the evolution of writing tools. Overall, this article provides valuable insights into the history, benefits, and challenges of writing in the digital age, as well as suggestions for navigating the future of writing and its tools.

The utilization of fermented foods has been a longstanding practice in human civilization worldwide for example sauerkraut from the Roman Empire, Jiangshui, and PaoCai, which are popular traditional foods in China. In Korea, Russia, and Mongolia, Kimchi and Kefir are widely used. Similarly, Japan, Indonesia, and Pakistan have their traditional fermented foods such as Miso, Natto, Tempeh, and sourdough, respectively. In America and Europe, fermented alcoholic beverages made from sorghum and maize are among the most common. Nevertheless, the full potential of fermented foods to enhance the bioavailability of bioactive compounds and restore probiotic communities has yet to be thoroughly explored. In this review, we focus on the bioactive compounds and probiotic stability in food fermented with probiotic bacterial strains. Probiotic fermented food improves the bioactive compound contents and has been gaining interest in basic and clinical research. Bioactive compounds, including phenolic, alkaloids, terpenoids, flavonoids, stilbenes, coumarins, tannins, anthocyanidins, flavones, isoflavonoids, and polyphenols, along with beneficial bacteria such as Lactobacilli, Bifidobacteria, Pediococcus, and Weissella demonstrate increased levels and restoration in probiotic fermented foods. These bioactive compounds, combined with a thriving microbiota, play a role in preventing viral infections by targeting influenza, noroviruses (NoVs), Murine norovirus-1 (MNV-1), and COVID-19, while also stimulating the host's immune function. Clinical and pre-clinical investigations are warranted to explore the dose-response and duration efficacy of probiotic fermented foods against viral infections.

The prevalence of digital devices in modern society has raised concerns about the potential neg-ative effects of blue light emissions on eye health and biological rhythms. Research into blue light emissions from digital devices and their potential impact on eye health emphasizes the importance of understanding and quantifying the extent and scope of blue light emissions produced by commonly used screens (smartphones, tablets and computers). This comparative study specifically evaluates three popular Apple devices: iPhone 12 mini®, iPad Pro 12.9® and MacBook Pro®. The devices' spectral power was measured using a spectroradiometer while displaying text and a game at different brightness levels. The study also examines the effectiveness of blue-blocking lenses from well-known brands. The research highlights the importance of quantifying blue light emissions and understanding their potential impact on eye health. By doing so, appropriate measures can be developed to mitigate adverse effects on ocular structures. Above all, this research provides valuable information about the risks associated with exposure to blue light, showing that all tested devices have blue wavelength peaks between 445 nm and 455 nm. By recognizing and addressing the potential negative impacts of blue light, the risks of eye health problems can be reduced and ensure more responsible and conscious use of digital devices.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

Globalization plays a very important role in the advancement of science and technology today, especially in Indonesia. Globalization has also succeeded in changing all aspects of human life. In addition to having a positive impact on the development of science and technology in Indonesia, globalization also has a negative impact that is quite visible on the character of today's youth. The crisis of the character of Indonesian youth is a serious matter and is reflected in the behavior of Indonesian youth today which does not coincide with the identity of the Indonesian nation and the values ​​of Pancasila. This paper examines the lack of implementation of Pancasila values ​​in the life of the globalization era and also how globalization affects moral decadence among the younger generation. The method used is the Literature Review method, which is a qualitative research method by collecting data from the literature. The lack of practice of Pancasila values ​​and the emergence of globalization is increasingly diminishing the character of Indonesian youth. The implementation of Pancasila values ​​among teenagers needs to be increased so that the nation's moral character is not eroded by the currents of globalization.

We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.

The past years saw the rise of genomic biobanks and mega-scale meta-analysis of genomic data that promise to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limit the global understanding of disease risk and intervention efficacy, but also inhibit viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared, and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable, computable, operate without access to raw data due to privacy concerns. But they must be comparable, both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of commonly used genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks, locally and internationally, increase the accuracy of association analyses, and inform developmental efforts.

In an era of global connectivity, language and literature education faces the challenge of navigating multilingualism, cultural diversity, and technological advancements. This paper explores the challenges and opportunities in language and literature education in the era of global connectivity. Through a qualitative research approach, interviews, focus group discussions, and classroom observations were conducted with 30 Arts and Sciences students and teachers. The findings reveal significant themes related to cultural diversity, multilingualism, and the integration of technology in language learning. The study emphasizes the importance of inclusive pedagogies, critical thinking development, and the incorporation of authentic and diverse literary works. Recommendations are provided for educators and policymakers to promote intercultural understanding and enhance language and literature education. The limitations of the study suggest areas for future research, including long-term language proficiency and diverse contextual considerations. Overall, this paper calls for ongoing innovation and collaboration to meet the evolving needs of language and literature education in an interconnected world.

Plant viral diseases constitute a major contributor to agricultural production losses, significantly impacting the economies of exporting countries by more than $30 billion annually. Understanding and researching the biology and genomics of viruses is crucial for developing virus-resistant, genetically edited or genetically modified plants. Genetic modifications can be targeted to specific regions within genes of target plants which are important or essential for the virus to establish a systemic infection, thus fostering resistance or enabling plants to effectively respond to invading agents while preserving their yield. This review provides an overview of viral incidence and diversity in tropical fruit crops and aims to examine the current state of the knowledge on recent research efforts aimed at reducing or eliminating the damage caused by viral diseases, with emphasis on genetically edited products that have reached the market in recent years.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

Novel drugs profoundly changed the outcomes in CLL patients and traditional prognostic/predictive factors that were delineated in the era of chemo-immunotherapy need to be validated in the contest of these new targeted therapies. Currently, the most important prognostic genetic biomarkers are immunoglobulin heavy chain variable (IGHV) mutational status, genetic aberrations including del(17p)/TP53 abnormalities and the complex karyotype. In this review we discuss the prognostic/predictive role of these genetic markers in relation to novel treatments. Moreover, we present and discuss the new score systems that were elaborated and validated in the era of new drugs. Given the deeper responses obtained with small molecules, new prognostic/predictive markers, including measurable residual disease, and validated prognostic scores could possibly be incorporated into routine prognostic scores, to better identify “very-high” CLL patients, who will need more effective treatments.

A significant number and range of challenges besetting sustainability can be traced to the actions and interactions of multiple autonomous agents (people mostly) and the entities they create (e.g., institutions, policies, social network) in the corresponding social-environmental systems (SES). To address these challenges, we need to understand decisions made and actions taken by agents, the outcomes of their actions, including the feedbacks on the corresponding agents and environment. The science of Agent-based Complex Systems—ACS science—has a significant potential to handle such challenges. The advantages of ACS science for sustainability are addressed by way of identifying the key elements and challenges in sustainability science, the generic features of ACS, and the key advances and challenges in modeling ACS. Artificial intelligence and data science promise to improve understanding of agents’ behaviors, detect SES structures, and formulate SES mechanisms.

As medical schools cope with the consequences of the COVID-19 pandemic, a new cohort of students will be admitted in the fall. Administrators are again challenged to make unprecedented enrollment decisions without standardized exams. This challenge provides unique opportunities to support holistic admissions but also abruptly bypasses a process that has been employed since 1928. This article highlights key factors that are being considered during current medical school admission cycles, including limited opportunities to take standardized exams, heightened student anxiety, and potential exam alternatives. These factors are framed and discussed within the context of the medical college admission test (MCAT) exam.

From 1964 to the early 1970s, Orson Anderson led a research program at the Lamont Geological Observatory in the newly-emerging field of “mineral physics”. In collaboration with colleagues Edward Schreiber and Naohiro Soga, Orson exploited the techniques of physical acoustics to study the behavior of the sound velocities of minerals at elevated pressures and temperatures. This research program also included semi-empirical studies of relationships between the bulk modulus and the molar volume of solids and the use of lattice dynamics to calculate the elastic moduli of cubic structures as a function of pressure to predict instabilities, as well as theoretical investigations of the Lagrangian vs. Eulerian formulations of finite strain equations of state.

Climate change refers to a wide range of changes due to unstructured economic and human activities that impact the well-being status of all living and non-living things. Many adaptation and mitigation strategies focus on climate change solutions, at the center of which is the replacement of fossil fuels or other conventional energy sources with renewables. Mainly this is a contemporary issue for economies that seek ways to grow sustainably, such as developing countries. The purpose of the present study is to review how these renewable sources might have brought benefits for environmental improvement efforts within intense economic activities. Our effort targets the case of China since its efforts for transmission to a low-carbon country attract the world's research interest, given its significance in the global economic system. Mainly, this study’s attempt is based on searching relevant literature for potential changes in limiting greenhouse and carbon dioxide emissions toward China’s economic development status. The results of this study aim to become a valuable reference for further elaboration in light of climate change strategies with measurable outcomes in the growth process.

This transdisciplinary review of research about international cooperation on social and environmental change builds the case for replacing Sustainable Development as the dominant framework for an era of increasing crises and disasters. The review is the output of an intentional exploration of recent studies in multiple subject areas, based on the authors’ decades of work in related fields since the Rio Earth Summit 30 years ago (rather than a keyword search of databases). It summarizes the research which documents failure to progress towards the Sustainable Development Goals (SDGs). Consequently, the extensive scholarship critiquing the conceptual framework behind those ‘Global Goals’, and the economic ideology they arose from and support, is used to explain that failure. Although the pandemic set back the SDGs, it further revealed the inappropriate strategy behind those goals. This suggests the Global Goals constitute an ‘own-goal’ scored against people and nature. From this conclusion, alternative frameworks for organizing action on social and environmental issues become more important and are therefore briefly reviewed. It is argued that such a future framework must relate a new eco-social contract between citizen and state, and engage existing organizations and capabilities that are relevant to an increasingly disrupted world. Therefore, the case is made for considering an upgraded form of Disaster Risk Management (DRM) as an overarching framework. The proposed upgrades include detaching from economic ideologies, and recognizing that a wider metadisaster from climate chaos may reduce the future availability of external support. Therefore, self-reliant resilience and locally-led adaptation are identified as important to the future of DRM. Some options for professionals continuing to use the term sustainability, such as this journal, are discussed.

While several studies have examined the impact of the Covid-19 pandemic on smallholder rural farmers and possible efforts to scale up their livelihood and food security, the role of consumers’ buying orientation in addressing farmers’ vulnerability in the post-pandemic era has not been explored. The paper, therefore, aims to propose and conceptualize humane buying orientation, and further explore its role in attenuating smallholder rural farmers’ vulnerability in the new normal. The qualitative design approach has been employed in two different studies. Collected data were analyzed using the SPSS 23.0 and following the interpretative phenomenological analysis. Findings validate humane buying as an altruistic orientation that will contribute to lessening the vulnerability of smallholder rural farmers in the post-pandemic era. It also shows that an enlarged-stakeholders’ (government, international agencies, corporate bodies, institutions, privileged individuals/consumers, religious organizations, etc.) effort that is rooted in morality and empathy, is required to successfully tackle the vulnerability of smallholder rural farmers, especially in developing countries such as Nigeria. The study is the first to propose, conceptualize and validate humane buying as a post-Covid-19 orientation that is capable of attenuating the vulnerability of smallholder rural farmers which has been worsened by the pandemic. The paper contributes to the understanding of emerging strategic actions required for the attainment of the United Nation’s sustainable development goals - ending poverty and hunger by 2030, and how consumers can play a key role.

Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In the advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in the OC. Methods: We searched the PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were selected, of which 16 were phase I or II and 4 phase III trials. ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, atezolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab) were employed. No significant survival improvement was achieved; conversely, early terminations due to futility or toxicity were recorded. Combinations with chemotherapy, anti-VEGF, and, overall, PARP-inhibitors seem feasible and enhance the response rate and survival, notwithstanding a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of the OC might lead to an improved treatments selection and design of tailored trials.

This study focuses on land cover and land management changes in relation to food security and environmental services in a semi-arid area of East Nusa Tenggara (ENT) – Indonesia. The study was conducted in Central Sumba District of ENT Province. Classification and regression tree (CART) for land cover classification has been analyzed using machine learning techniques using Google Earth Engine. A survey with Focus Group Discussion (FGD) and followed with in-depth interviews were conducted for primary data collection involving a total of 871 respondents. The Socio-economic data analyzed statistics descriptively and non-parametric tests. The study showed that: 1). There has been a substantial land use change during the devo-lution era that has both positive and negative implications for food security and envi-ronmental services. 2). There has been population pressure in the fertile or agricultur-al land as the direct impact of the development of city infrastructures; and 3). Nation-al intervention through the Food Estate program has fostered and shaped land use change and land management in Central Sumba District. The study highlights the importance that the devolution spirit should help to well manage the limited ara-ble/agricultural land in dominated semi-arid to ensure food security and environment services.

Health services research is a multidisciplinary discipline that aims to improve population health by studying healthcare services' organization, delivery, and financing. Over time, the field has worked to define its boundaries and establish a set of core research topics and methods addressing population wellbeing, access, quality, and cost. Although the influence of health technology is significant, our literature survey on health services research showed that SCs in general—containing their management, cost, and policy—had received little attention. Importantly, our assessment also showed that the system’s readiness to handle supply policy and supply device deficiencies like those encountered during pandemic was hardly ever mentioned. Reduced open areas and water bodies, deteriorating infrastructure, and changes in the biological morphology all affect cities’ uncontrollable and unplanned growth. Urban amenities, facilities, and healthcare services were unevenly distributed due to this unchecked urban population development. In light of this, this research suggests two reliable models for site selection issues for one of Hong Kong’s main hospitals. Levels of uncertainty, infeasibility tolerance, and reliability are taken into consideration. Then, two categories of uncertainty—symmetric and bound-ed—were examined. As a result, the challenge of scheduling in uncertainty has been considered, and potential solutions have been presented using a specified probability distribution function. The paper concludes by introducing the specific justice and health problems and outlining four typical strategies. In order to ensure that medications and other healthcare supplies are produced, distributed, and given to patients, a vast network of systems, components, and procedures must be effectively managed. This research contributes in this regard. Also, its grantee fairness in health systems and the populations health locally, nationally, and globally. It highlights health inequity, advances the measurement of health inequity, and promotes public dialogues on health inequity.

The article examines the relationship between household food waste and GDP in various European regions, aiming to determine how economic prosperity influences household food waste levels. Using comparative analysis of secondary and tertiary data, we developed a synthetic indicator (IpFW), to assess the interaction between GDP per capita and household food waste per capita. Despite expectations, higher GDP did not consistently correlate with lower food waste, challenging assumptions about economic prosperity and environmental stewardship. The research underscores the complex interplay between economic factors and food waste management, revealing no significant correlation even at regional levels. It also highlights the potential of e-commerce in enhancing food waste reduction strategies. E-commerce platforms can optimize food supply chains and consumer behavior, contributing to more sustainable consumption patterns. The conclusions call for a reevaluation of policies and suggest that integrating e-commerce could bolster efforts to manage food waste more effectively, aligning with the Sustainable Development Goals.

This study delves into the dynamic intersection of artificial intelligence (AI) and English Language Teaching (ELT) within the post-pandemic educational landscape. Grounded in Constructivism, Connectivism, and Technological Pedagogical Content Knowledge (TPACK), this research explores how AI integration impacts language instruction efficiency, benefits and challenges perceived by St. Michael's College students, differences in learning outcomes, and its potential to address the digital divide. Employing a qualitative approach, the study employs a rigorous method that includes intensive in-depth reviews of literature, maximum purposeful sampling, informal interviews, observation, and thematic analysis. Through these methods, data was collected from 30 participants, leading to the identification of five key themes. Findings suggest that AI enhances instructional efficiency, offers personalized learning experiences, and bridges gaps in remote settings. However, challenges and the importance of pedagogical balance emerged. The study underscores the need for adaptive pedagogical strategies to fully harness AI's potential. Future directions and limitations are discussed, emphasizing the study's implications for shaping the future of ELT.

The COVID-19 pandemic has invited us to envision education anew, embracing a new era of instructional practices and learning environments. This study explores language teachers' and students' experiences in the post-pandemic landscape, providing valuable insights into the challenges, adaptations, and opportunities. Grounded in socio-cultural perspectives and educational theories, such as Vygotsky's socio-cultural theory and Deci and Ryan's self-determination theory, the study employs Interpretative Phenomenological Analysis (IPA) to comprehensively analyze secondary data sources. Findings reveal the significant role of social interaction and cultural context in language learning, amid reduced face-to-face contact and increased reliance on technology. The study uncovers the intricate interplay between individual, interpersonal, and environmental factors, shedding light on educators' and learners' challenges. Autonomy, competence, and relatedness emerge as crucial for intrinsic motivation and optimal learning outcomes. While acknowledging limitations related to secondary data sources, the study offers a comprehensive overview of the literature, informing language education practices in the post-pandemic era. It contributes to understanding the complex dynamics and interactions within language education and calls for future research using primary data collection methods to explore experiences and perspectives further. By understanding post-pandemic experiences, this study aims to shape education policies, practices, and pedagogical approaches, supporting effective language learning and the well-being of educators and learners in this transformed educational context.

Acute promyelocytic leukemia (APL) currently represents one of the malignant hemopathies with the best therapeutic responses following the introduction of all-trans retinoic acid (ATRA) and later of arsenic trioxide (ATO) treatment. As a result, patients with APL achieve long-term responses in a large proportion after first-line therapy, so that performing hematopoietic stem cell transplant as consolidation of first complete remission is no longer necessary. Even in the case of relapses, most patients obtain a new remission thanks to the therapy with ATO and ATRA, but to maintain it, a consolidation treatment as effective as possible is necessary. The experience accumulated from studies published in the last two decades shows the effectiveness of hematopoietic stem cell transplantation (HSCT) in improving the evolution of patients who achieve a new complete re-mission. Thus, the recommendations of expert groups indicate transplantation as consolidation therapy in patients with a second complete remission with the mention of the use of autologous HSCT in cases with complete molecular remission and allogeneic HSCT for patients with the persistence of minimal residual disease or early relapse. However, there is a variety of contro-versial aspects related to the role of HSCT in APL, from obtaining outcome data almost exclusively from retrospective studies and historical analyzes to questions related to the type of transplanta-tion, the impact of minimal residual disease, conditioning regimens, or the role of other thera-peutic options. All these questions justify the performance of controlled prospective studies in the following years.

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss management of older adults and transplant-ineligible patients who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

The indications for TACE in the treatment of hepatocellular carcinoma have become more stringent with the development of systemic pharmacotherapy. Radical TACE is expected to be used only in situations such as for tumors with small volume which fulfill the “up-to-7”. Furthermore, a combination of molecular-targeted agents is expected to maximize the efficacy of TACE. In the intermediate stage, TACE and drug therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no studies have investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into conventional TACE, balloon occluded TACE (B-TACE), and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for hepatocellular carcinoma in the drug therapy era.

The development of quantum computers seeks software developers' attention regarding security in the era of Information Technology, software security is the primary goal for our quantitative assessment of software security in the development cycle of software. Security assessment of software is identifying the key security factors of the software. A security elective provides ex-tensive strategies and calculations to ensure product safety. The security assessment is the key factor in surveying, administering, and controlling security to further enhance the nature of safety. It should be acknowledged that assessing security early on in the development process is beneficial in identifying worms, hazards, flaws, and threats. The definition and portrayal of Quantum Computing (QC) in software security will be discussed in this study. Researchers use cryptography calculations to secure our financial institutions, medical devices, military weaponry, planes, ships, vehicles, and pilots. Here authors of this study use the Fuzzy Technique for Order Preference by Similarity to Ideal Situation (FTOPSIS) to quantitatively assess the weight/rank of the quantum enable security alternatives like (Diffie-Hellman key-exchange algorithm, Quantum key distribution algorithm, Deutsch-Jozsa Algorithm, Special Deutsch-Jozsa Algorithm, Grover’s Algorithm and Quantum key distribution algorithm in GHZ state) with security factors like (Confidentiality, Integrity, Authenti-cation, Privacy, Reliability, Maintainability, Authorization, Integrity, Possessions, and Availability). Additionally, they critically analyze and select the six alternatives of quantum-based security algorithms. The nature of safety infers the ability to execute a thing on time in this exploration study, specifically 'software security'.

Character education is essential for the current millennial generation and must be applied in everyday life in the surrounding community. The character of the millennial generation is different from the previous generation, which requires us to pay more attention to character education which is starting to erode along with the times. The Millennial generation is a generation that in everyday life can never be separated from science and technology. In this digital era, the millennial generation has a social function of strength in technology. In this study, there are research questions that will be discussed in this article, namely the first regarding what problems occur in the millennial generation who occupy the digital era?. Second, what is the important role and influence of the digital era on character education for the millennial generation in Indonesia?. Writing this article uses a qualitative research method, namely a literature review study, where researchers use or look for references from journals or books. Samples of respondents were taken randomly from each region, and there were ten respondents. From this research, it is found that the millennial generation in the digital era chooses to use social media to access the latest news and information rather than reading print media that contains education. This article aims to find out the importance of character education for the millennial generation, which is starting to erode with the times in the digital era. Many people underestimate character education, especially for the current millennial generation. Therefore, we must implement educational programs at any level, especially in Indonesia, because the character shows the national identity. This article will discuss the vital role and influence of character education for millennials who live in the digital era to be aware of the importance of character education in citizenship.

Background: The rapid flow of globalization makes the world free from barriers so that the existence of globalization gives birth to a new concept of "World Without Borders". This situation puts the character of millennials on the brink of collapse and needs to be straightened out. Based on the problems above, the researcher determines the question: How is the role of civic education in shaping millennial character in the era of globalization? Purpose: The purpose of this study is to determine the impact of the current globalization on society, as a form of knowledge of the importance of citizenship education as a shield in the era of globalization, knowing the role of civic education in shaping the character of the millennial generation. Method: The method used in this research is a literature review. The search for journals was carried out using the google scholar database with the keywords “citizenship educations”, “millennial generation”, and “globalization”. Feasibility studies are assessed based on title, abstract, and full text. Data analysis using qualitative analysis based on research findings. Results: The results of this study show the influence of globalization causes character problems in millennials increasing every year. The high nature of individualism, consumerism, and westernization shows the characteristics of Indonesia began to erode and eventually also impacted the moral damage. Therefore, prevention is necessary through citizenship education as the basis for character formation by the values of Pancasila.

Background: The rapid flow of globalization makes the world free from barriers so that the existence of globalization gives birth to a new concept of "World Without Borders". This situation puts the character of millennials on the brink of collapse and needs to be straightened out. Based on the problems above, the researcher determines the question: How is the role of civic education in shaping millennial character in the era of globalization? Purpose: The purpose of this study is to determine the impact of the current globalization on society, as a form of knowledge of the importance of citizenship education as a shield in the era of globalization, knowing the role of civic education in shaping the character of the millennial generation. Method: The method used in this research is literature review. The search for journals was carried out using the google scholar database with the keywords “citizenship educations”, “millennial generation”, and “globalization”. Feasibility studies are assessed based on title, abstract, and full text. Data analysis using qualitative analysis based on research findings. Results: The results of this study show the influence of globalization causes character problems in millennials increasing every year. The high nature of individualism, consumerism, and westernization shows the characteristics of Indonesia began to erode and eventually also impacted the moral damage. Therefore, prevention is necessary through citizenship education as the basis for character formation by the values of Pancasila.

After human genome sequencing and rapid changes in genome sequencing methods, we have entered in the era of rapidly accumulating genome-sequencing data. This has poses development of several types of methods for representing results of genome sequencing data. Circular genome visualizations tools are also critical in this area as they provide rapid interpretation and simple visualization of overall data. In the last 15 years, we have seen rapid changes in circular visualization tools after the development of the circos tool with 1–2 tools published per year. Herein we have summarized and revisited all these tools until the third quarter of 2018.

In the era of disruption, to achieve food sustainability and the SDGs, Indonesia is faced with changes in the values, attitudes, and behavior of the community to be adaptive to environmental and technological changes. This study aims to analyze the factors that influence social transformation in peri-urban communities and their impact on food sustainability and the achievement of SDGs. The research method is a qualitative approach, triangulated by conducting in-depth interviews, field observations, and focus group discussion (FGD) in two districts. The results showed that factors influencing social transformation in peri-urban communities include: strengthening public awareness of the importance of food sustainability, access to information and technology, collaborative synergetic of government, companies, academics, and community participation in decision-making on empowerment programs. This social transformation leads to increased food production and poverty reduction. Private facilitators through CSR programs play a role in achieving food sustainability and achieving several SDG indicators related to poverty. The occurrence of collaborative synergetic between community participation, extension workers, village government, media utilization, academics, and companies contributes significantly to transforming the values, attitudes, and behavior of people managing community resources.

Introduction: The imbalance between technological development and ideological strengthening has resulted in the fading of the Pancasila ideological values of millennials. Technology that accompanies everyday life seems to be the main character in human life. Yet if humans themselves do not use technology wisely, technology can be a threat to both individuals and the life of the nation and state. If technology is increasingly out of control, threats to the Pancasila ideology are very likely to occur, such as in the G 30S PKI incident. Therefore, it is necessary to take action both from the government and the community as individuals to safeguard the development of technology to be used wisely. That way, we can prevent the threat to the Pancasila ideology together. Writing this article aims to analyze how the role and influence of the Pancasila ideology on the millennial generation in the 4.0 industrial revolution and to find solutions so that the values of Pancasila remain attached to the next generation of the Indonesian nation. Method: Writing This article uses a qualitative method by using literature reviews from the results of related research journals that have been published online through websites and other online media. Results: Thirteen journals and one book have met the criteria for the inclusion of a predetermined review. Research is based on the stigma of society regarding technological developments in the Industrial revolution 4.0. Therefore, the government is expected to be more severe in implementing human capital management. Conclusion: By procuring human capital management, it will be possible that Human Resources (HR) in Indonesia will be able to carry out the ideals of a golden Indonesian generation with Pancasila values inherent in the hearts of the people and the nation's future generations.

The COVID-19 pandemic has put lifestyles in question, changed daily routines and limited citizen freedoms that seemed inalienable before. A human activity that was greatly affected since the beginning of the health crisis is mobility. Focusing on mobility, we aim to discuss the transformational impact that the pandemic brought on this specific urban domain, especially with regards to the promotion of the smart growth agenda and the acceleration towards the smart city paradigm. We collect 60 initial policy responses related to urban mobility from 86 cities around the world and analyse them based on the challenge they aim to address, the exact principles of smart growth and sustainable mobility that they encapsulate and the level of ICT penetration. Our findings suggest that emerging strategies, although mainly temporary, are transformational, in line with the principles of smart growth. As a result the pandemic becomes an opportunity for shifting towards more sustainable urban planning and mobility practices. However, most policy responses adopted during the first months of the pandemic fail to leverage advancements made in the field of smart cities, and to adopt off-the-shelf solutions such as in monitoring, alerting and operations management.

Central Nervous System (CNS) cancers pose a formidable challenge in the medical world, characterized by aggressive behaviors and limited therapeutic options. The emergence of nanomedicine has offered new hope in CNS cancer treatment. The COVID-19 pandemic has further accelerated the need for innovative therapeutic strategies, emphasizing the significance of nanomedicine in this era. This mini review explores the current status of nanomedicine in CNS cancer therapy, with a particular focus on the post-COVID-19 landscape. We discuss the unique challenges presented by CNS cancers, the potential of nanomedicine in overcoming these challenges, and the recent developments in the field. Additionally, we highlight the lessons learned from the pandemic and how they can be applied to improve CNS cancer therapeutics. We also shed light on the evolving regulatory landscape and the prospects of personalized nanomedicine in CNS cancer treatment. The integration of nanomedicine in CNS cancer therapy is becoming increasingly promising, and its role in the post-COVID-19 era is poised to shape the future of neuro-oncology.

This article explores the concept of sustainable leadership in the digital era and the role of technology in promoting environmental sustainability. As the world becomes increasingly interconnected through digital advancements, leaders are facing new challenges and opportunities to address environmental concerns. This article examines the key characteristics of sustainable leadership and discusses how technology can be utilized to promote environmental sustainability. It highlights various technological innovations and strategies that leaders can employ to foster a sustainable organizational culture. Moreover, the article discusses potential barriers and limitations of technology in achieving sustainability goals. Overall, it emphasizes the significance of sustainable leadership and technology integration in addressing environmental challenges in the digital era.

Chikungunya, Dengue, and Zika viruses are endemic to Brazil, with a high annual incidence rate. It is a serious public health issue and is responsible for outbreaks and epidemics worldwide. As COVID-19 emerged as a pandemic, the diagnosis of arboviruses was underestimated. Hence, this study aimed to characterize the sociodemographic and clinical aspects of arboviruses in the con-text of the COVID-19 pandemic in the state of Maranhão, Brazil. Sociodemographic and clinical data were obtained by applying questionnaires to 179 patients treated at health units in São José de Ribamar, Paço do Lumiar, Raposa, Santa Inês, and Vargem Grande municipalities. Serologi-cal and polymerase chain reaction analyses were performed do detect Chikungunya, Zika, Den-gue, and COVID-19 infections. The Maranhão state registered 706 probable cases of Chikungunya from 2019 to 2020. In 2020, the cases were reduced by 74.8% compared to those reported in 2019. The test results were analyzed separately. Here, 46.3% of the Chikungunya virus test results were negative, and 36.8% were positive. For the Zika virus tests, most (79.9%) were positive, as well as the DENV1, DENV2, DENV3, and DENV4 tests (88.3%, 88.3%, 89.4%, and 65.9%, respectively). For the COVID-19 tests, of the 146 individuals tested, 52.7% were reactive when considering the anti-S test, and 17.8% were positive when considering the anti-N test. Fever and myalgia were the symptoms most frequently reported by patients. Our results emphasize the importance of contin-uous epidemiological surveillance of arboviruses in northeastern Brazil, and simultaneous test-ing for Chikungunya, Dengue, and Zika viruses among suspected patients.

This study explored the living situations, financial conditions, religious obligations, and social distancing of Muslims during the covid 19 pandemic. In total, 20 Muslim community members living in the Kanto region were recruited, 15 of them were included in the in-depth qualitative and five in the focus group interviews. The Snowball method was used, and the questionnaires were designed into four themes. The audio/video interviews were conducted via Zoom and NAVIO was used to analyse the data thematically. The major Muslim events were cancelled, and the recommended physical distancing was maintained during the prayers at home and in the mosques. The Japanese government's financial support to each person was a beneficial step towards social protection, which was highlighted and praised by every single participant. Regardless of religious obligations, the closer of all major mosques in Tokyo demonstrates to the Japanese community how serious they are about adhering to the public health guidelines during the pandemic. This study highlighted that the pandemic has affected the religious patterns and behaviour of Muslims from inclusive to exclusive in a community and narrated the significance of religious commitments.

Among all economically important plant species in the world, grapevine (Vitis vinifera L.) is the most cultivated fruit plant. It has a significant impact on the economies of many countries through wine and fresh and dried fruit production. In recent years, the grape and wine industry has been facing outbreaks of known and emerging viral diseases across the world. Although high-throughput sequencing (HTS) has been used extensively in grapevine virology, the application and potential of third-generation sequencing have not been explored in understanding grapevine viruses and their impact on the grapevine. Nanopore sequencing, a third-generation technology, can be used for direct sequencing of both RNA and DNA with minimal infrastructure. Compared to other HTS methods, the MinION nanopore platform is faster and more cost-effective and allows for long-read sequencing. Due to the size of the MinION device, it can be easily carried for field viral disease surveillance. This review article discusses grapevine viruses and their diagnostic methods, the principle of nanopore sequencing technology and its application in grapevine virus detection, virus–plant interactions, as well as the characterization of viral RNA modifications.

The prevalence of obesity or metabolic syndrome is increasing worldwide (“Globally metabodemic”). Approximately 25% of adult general population is suffering from nonalcoholic fatty liver disease (NAFLD) which has become serious health problem. Hepatic fibrosis is the most significant determinant of all cause and liver -related mortality in NAFLD. Noninvasive test (NIT) should be urgently required to evaluate hepatic fibrosis in NAFLD. Fibrosis-4 (FIB-4) index is the 1st triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness especially for general physicians or endocrinologists, although FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the 2nd step after triaging by FIB-4 index. The leading cause of mortality in NAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. NAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation (SLKT). FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocullar carcinoma (HCC) but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, FIB- 4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of FIB-4 index as 1st step NIT in management of NAFLD.

Although genome-wide association studies (GWAS) have identified several hundred loci associated with autoimmune diseases, their mechanistic insights are still poorly understood. The human genome is more complex than common single nucleotide polymorphisms (SNPs) that are interrogated by GWAS arrays. Some structural variants such as insertions-deletions, copy number variations, and minisatellites that are not very well tagged by SNPs cannot be fully explored by GWAS. Therefore, it is possible that some of these loci may have large effects on autoimmune disease risk. In addition, other layers of regulations such as gene-gene interactions, epigenetic-determinants, gene and environmental interactions also contribute to the heritability of autoimmune diseases. This review focuses on discussing why studying these elements may allow us to gain a more comprehensive understanding of the aetiology of complex autoimmune traits.