Thyroid hormones are essential for regulating the metabolic rate, growth, development, and maintenance of many physiological processes in vertebrates. They are synthesized by the thyroid gland, which is an ancient organ that evolved early in vertebrate evolution. This study aims to characterize the evolutionary path of polymorphic variants associated with the hypothalamus-pituitary-thyroid (HPT) axis by comparing ancient DNA (aDNA) sequences of Late Pleistocene-Holocene hominin populations with those of modern humans. We evaluated the genetic sequences of several populations, including Neanderthals, Denisovans, Palaeolithic hunter-gatherers from European Russia and Sunghir, and Neolithic hunter-gatherers/farmers from Anatolia focusing on genes involved in the development of the thyroid gland and thyroid hormone (TH) biosynthesis, secretion, and transport. Results showed interesting variants in the DIO2 (rs225014), TPO (rs4927611), and TG (rs2069556 and rs1133076) genes. All SNPs seemed to confirm that Neanderthals, and in part Denisovas, were physiologically hypothyroidic. Probably they had lower T3 levels due to defective production or peripheral conversion. From the moment that the most favourable alleles in terms of T3 production appear during the Paleolithic, we are inclined to assume that their selection was linked to environmental pressure.Our study supports insight into the evolutionary history of the endocrine system and can help in providing understanding into the evolution of physiological systems and their adaptation to changing environments. Understanding the evolution of thyroid hormones can also shed light on the mechanisms underlying thyroid disorders in humans.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Introduction: Parameters used for neonatal mortality calculation vary among publications. Mortality in < 33 weeks gestational age at birth display global variations across different healthcare units. Objective: This study aims to explore trends in neonatal mortality among infants born preterm in the different units in Latin America and the Caribbean utilizing the EpicLatino Network Database in comparison to Canadian Neonatal Network (CNN) 2022. Materials and Methods: This study focused on an eight-year period, with a particular attention to mortality rates during the pre-pandemic (2015-2019) and pandemic/post pandemic (2020-2022) periods. Survival rates from CNN 2022 were included in the comparison analysis. Logistic regression analysis was confined to the 2020-2022 period. Adjustments were made for factors including gestational age, small for gestational age (SGA), Snape II score, inborn/outborn status, and center. As major malformations could account for mortality differences among units. The incidence of major congenital malformations, as defined by CNN, was compared among deceased patients. Results: A total of 15,454 records from 2015-2019 and 10,711 records from 2020-2022 were scrutinized. Overall, there were no significant differences in mortality rates between the two time periods (p=0.22). Moreover, the originating unit during the 2020-2022 period significantly influenced all statistical computations. Conclusions: Survival rates among infants < 26 weeks of gestation in Latin America and the Caribbean are on an upward trajectory, with the healthcare unit playing a pivotal role in this outcome within the EpicLatino database. Major malformations do not seem to be a significant contributing factor. These findings underscore the imperative of implementing quality improvement initiatives to elevate neonatal care standards in Latin America and the Caribbean.

In genetic conflicts, driver and killer elements achieve biased survival, replication, or transmission over sensitive and targeted elements through a wide range of molecular mechanisms, including mimicry. Driving mechanisms manifest at all organismal levels, from the biased propagation of individual genes, as demonstrated by transposable elements, to the biased transmission of genomes, as illustrated by viruses, to the biased transmission of cell lineages, as in cancer. Targeted genomes are vulnerable to molecular mimicry through the conserved motifs they use for their own signaling and regulation. Mimicking these motifs enables a selfish element to control core target processes, and can occur at the sequence, structure, or functional level. Molecular mimicry was first appreciated as an important phenomenon more than twenty years ago. Modern genomics technologies, databases, and machine learning approaches offer tremendous potential to study the distribution of molecular mimicry across genetic conflicts in nature. Here, we explore the theoretical expectations for molecular mimicry between conflicting genomes, the trends in molecular mimicry mechanisms across known genetic conflicts, and outline how new examples can be gleaned from population genomic datasets. We discuss how mimics involving short sequence-based motifs or gene duplications can evolve convergently from new mutations. Whereas, processes that involve divergent domains or fully-folded structures occur among genomes by horizontal gene transfer. These trends are largely based on a small number of organisms and should be reevaluated in a general, phylogenetically independent framework. Currently, publicly available databases can be mined for genotypes driving non-mendelian inheritance patterns, epistatic interactions, and convergent protein structures. A subset of these conflicting elements may be molecular mimics. We propose approaches for detecting genetic conflict and molecular mimicry from these datasets.

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly-large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remains elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

This paper is a brief review of our own work on the Planck quantized version of general relativity theory. It demonstrates several other straightforward methods to simply rewrite the same equations that we have already presented.

We will demonstrate that the photon energy density parameter Ωγ of the universe can be derived exactly in Rh = ct cosmology. We find that it must be Ωγ = 1/5760π ≈ 5.52621330180192× 10^(−5). This indicates that there is no uncertainty in the radiation density within at least somesub-classes of Rh = ct cosmology.

This work addresses the intricate task of predicting the prices of diverse financial assets, including stocks, indices, and cryptocurrencies, each exhibiting distinct characteristics and behaviors under varied market conditions. To tackle the challenge effectively, a novel hybridized architecture, AE-GRU, integrating the encoder-decoder principle with GRU is designed. The experimentation involves multiple activation functions and hyperparameter tuning. With extensive experimentation and enhancements applied to AE-LSTM, the proposed AE-GRU architecture still demonstrates significant superiority in forecasting the annual prices of volatile financial assets from multiple sectors mentioned above. Thus, the novel AE-GRU architecture emerges as a superior choice for price prediction across diverse sectors and fluctuating market scenarios by extracting important non-linear features of financial data and retaining the long-term context from past observations.

Suppose for n∈ ℕ, set A⊆ℝⁿ and function f∶A→ℝⁿ. If set A, using the Hausdorff outer measure, is measurable in the sense of Carathèodory; we want to find an extension of the expected value, w.r.t the Hausdorff measure, that's unique, finite and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. The issue is current extensions of the expected value are finite for all functions in only a shy subset of ℝᴬ. The reason this issue wasn't resolved is mathematicians have not thought of the problem, focusing on application rather than generalization. Despite the lack of potential use, we'll attempt to solve the problem by defining a choice function---this shall choose a unique set of equivalent sequences of sets (Fₖ***) , where the set-theoretic limit of Fₖ*** is the graph of f; the measure Hʰ is the ℎ-Hausdorff measure, such for each k∈ℕ, 0 < Hʰ(Fₖ***) < +∞; and (fₖ*) is a sequence of functions where {(x,fₖ*(x))∶x∈ dom(Fₖ***)}=Fₖ***. Thus, the extended expected value of or E**[f,Fₖ***] is: ∀(ε>0)∃(N∈ℕ)∀(k∈N)(k≥N⇒1/Hʰ(dom(Fₖ***))∫dom(Fₖ*** )fₖ* dHʰ - E**[f,Fₖ***]<ε ) which should be unique, finite, and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. Note we guessed the choice function using computer programming but we don’t use mathematical proofs due to the lack of expertise in the subject matter. Despite this, the biggest use of this research is the extension of the expected value is finite for "almost all" functions: this is easier to use in application when finding the "average" of functions covering an infinite expanse of space.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Cucurbitacin phytonematicides consistently suppress population densities of plant nematodes, but have no effect against bacteria, fungi and insects. This study investigates the mechanism through which cucurbitacin phytonematicides consistently exert nematicidal properties on nematodes. Post 72-h exposure of second-stage juveniles (J2) of Meloidogyne enterolobii to geometric concentration of Nemafric-BL phytonematicide, J2 total proteins were measured using TruspecCHNS Macro. Total proteins versus phytonematicide exhibited a negative quadratic relation (R² = 0.97), with the minimum total proteins achieved at x = 4.9% phytonematicide. Beyond the minimum, total proteins increased gradually, depicting the existence of both isoprenylation (breakdown) and farnesylation (biosynthesis) of total proteins. In conclusion, cucurbitacins and nematode cuticles are both chemically structured, which provides the mechanism through which the test chemicals consistently decrease population densities of plant nematodes.

Based on recent progress in cosmological thermodynamics, we present a new thermody- namic formulation of the Friedmann equations in the new Haug-Tatum cosmology model, as well as for other similar models put forward in the literature from different solutions to Einstein’s field equation. Since the CMB temperature has been measured much more accu- rately than the Hubble constant, we demonstrate that our thermodynamic formulation of the Friedmann equation dramatically narrows the acceptable range for the critical density of the universe. Furthermore, we show how our thermodynamic formulation leads to a more precise cosmological constant estimate.

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

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

Blockchain technology has emerged as a necessity for the decentralization of payment methods and transactions, but it has brought with it many properties of distributed systems that have made it a crucial technology for overcoming some of society's challenges, especially in the context of decentralizing services, transparency of information, availability, and security. Its architecture and communication methods, although possessing some complex nuances to understand, particularly for the lay audience in the field of distributed systems, protocols, and computer networks. In this article, we will explore some topics of distributed systems related to blockchain technology.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

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

Efficient triaging and referral assessment are critical in ensuring prompt medical intervention in the Community Health Care (CHC) system. However, the existing triaging systems in many Community Health Services are an intensive, time-consuming process and often lack accuracy, particularly for various symptoms that might represent heart failure or other health-threatening conditions. There is a noticeable limit of research papers describing AI technologies for triaging patients. This paper proposes a novel quantitative data-driven approach using machine learning (ML) modelling to improve the community clinical triaging process. Furthermore, this study aims to employ the feature selection process and machine learning power to reduce the triaging process’s waiting time and increase accuracy in clinical decision-making. The model was trained on medical records of “Heart Failure” patients’ dataset, which included demographics, past medical history, vital signs, medications, and clinical symptoms. A comparative study was conducted using the list of machine learning algorithms where XGBoost demonstrated the best performance among other ML models. The triage levels of 2,35,982 patients achieved an accuracy of 99.94%, precision of 0.9986, recall of 0.9958, and f1-score of 0.9972 within 0.059 seconds. The proposed diagnostic model can be implemented for the CHC decision system and be developed further for other medical conditions.

This review paper delves into the multifaceted aspects of pineapple cultivation, focusing on morphology studies, harvesting challenges, and mechanization efforts. Pineapple, renowned for its commercial value and unique flavor, holds a prominent position in global agriculture, with India alone producing 19.64 lakh tonnes annually. However, the hilly terrains of regions like northeastern India pose significant hurdles to traditional harvesting methods, necessitating innovative solutions. Understanding the morphology of pineapple plants is crucial for optimizing cultivation practices and designing efficient harvesting equipment. Insights from various studies shed light on leaf structure, fruit maturity, and growth patterns, providing valuable information for engineering tailored solutions. Mechanization endeavors, including semi-mechanized harvesting machines and semi-manual harvesters, demonstrate promising results in improving efficiency and reducing labor-intensive practices. Despite challenges such as increased crop losses and operational costs, continued research and development in mechanization hold the key to sustainable pineapple cultivation. This paper underscores the importance of integrating morphology studies and mechanization efforts to address the unique challenges faced by pineapple farmers, particularly in hilly terrains, and highlights the need for ongoing innovation to ensure the long-term sustainability of pineapple cultivation.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

Abstract Introduction: Poor structural quality of health facilities for tuberculosis (TB) diagnosis and treatment contributes to unfavorable health outcomes among TB patients. Improving the quality of healthcare services helps to avert TB-related morbidity. Despite these facts, the level of structural quality of health facilitieSs to deliver TB services is not in line with what the national TB and leprosy program (NTLP) recommends. Hence, the present study was conducted to assess the structural quality of health facilities to deliver quality TB services to TB patients among public health facilities in the Sidama region.Objectives: To determine the quality of the structural domain of TB services at public health facilities in the Sidama region of southern Ethiopia.Methods: An institution-based cross-sectional study was conducted from June to July 2023 among randomly selected public health facilities in the Sidama region. We included 40 randomly selected public health facilities that delivered TB services in the study area. Data was collected by experienced data collectors using facility audits, clinical observation checklists, structured questionnaires, and in-depth interviews. An Open Kit Mobile (ODK) application was used to collect data and exported to SPSS version 26. All statistical analysis was done using SPSS version 26.Results: The overall mean quality score for the structural dimension was 50.25 among the 40 health facilities audited in the study area.Conclusion: The quality of TB services regarding structural dimensions was poor in the study area. Therefore, any strategies must give careful attention to increasing the comprehensive structural dimension of quality TB services.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

Improving the level of farmers' participation in collective action is an important way to promote rural revitalization and improve the sustainable livelihood level of farmers in underdeveloped areas. Based on 312 questionnaires of farmers in Shanxi Province, this paper investigates the status of farmers' participation in collective action, their sustainable livelihood level and the sustainable livelihood effect of collective action participation. The results show that: farmers' willingness to participate in collective action is strong, and the participation effect is obvious, but the participation frequency is low, and the participation time is less; The farmers' sustainable livelihood level is relatively low, Empirical research shows that the level of collective action participation will have a significant positive impact on Farmers' livelihood risk prevention, livelihood capital accumulation, livelihood mode selection and livelihood income improvement, and the frequency, time and value perception of participation in collective action will have varying degrees of impact on Farmers' sustainable livelihoods. In order to promote farmers' active participation in collective action, it is proposed to strengthen the construction of collective organizations Provide incentives and improve the quality and skills of farmers to enhance the collective concept and other policy recommendations.

Graph databases (GDBs) are becoming increasingly popular across scientific disciplines, being highly suitable to store and connect complex heterogeneous data. In systems biology, they are used as a backend solution for biological data repositories, ontologies, networks, pathways, and knowledge graph (KG) databases. In this review, we analyse all publications using or mentioning graph databases retrieved from PubMed and PubMed Central full-text search, focusing on the top 16 available GDB technologies. Relevant publications are then categorised according to their domain and application. We detail different approaches and highlight advantages of outstanding resources, such as UniProtKB, Disease Ontology, and Reactome, which provide graph-based solutions. We discuss ongoing efforts of the systems biology community to standardise and harmonise KG creation and the maintenance of integrated resources. Outlining prospects, including the use of GDBs as a way of communication between biological data repositories, we conclude that efficient design, querying, and maintenance of GDBs will be key for knowledge generation in systems biology and other research fields with heterogeneous data.

Building defects are very prevalent and contribute significantly to a building's economic value. There are numerous information sources on building defects that have a lot potential for learning more about building defects. This study aimed to identify the information sources used in previous building defect studies and to identify the motivation for carrying out such studies. To fulfil this aim a scoping study was carried out. The information sources identified included insurance companies, private databases, questionnaire surveys, lawsuits, building surveys, client complaint forms, and maintenance reports. This study found that insurance company and client complaint forms include the largest collection of real building defect cases, but such databases may lack detailed descriptions of the causes of the defects. The main purposes of building defects studies identified here included design challenges, identification of defects, building maintenance management, quality management, systematization in data collection, providing an overview of typical defects, and classifying defects. Identification was found to be the most common purpose, indicating that the industry wants to learn more. This study identified research gaps in the climate perspective in relation to building defects. Most of the studies focused on the economical perspective, and none focused on the carbon footprint perspective.

With the trend of public infrastructure becoming more sustainable, large multi-purpose sports venues (LMPSVs) have become one of the world's most complex architectural projects and one of the landmark buildings of an international city. LMPSVs will lead the world in sustainable design, construction and operational innovations, and play a crucial role in raising awareness of sustainability around the world. System Thinking (ST), System Dynamics (SD) and Sustainable System Development (SSD) theories are three interrelated concepts that together form a methodological framework for solving complex system problems and driving strategies. The purpose of this study is to examine how LMPSVs can implement environmental, social, governance, and innovation (ESGI) enterprise transformation strategy (ETS) based on a sustainable systems development (SSD) framework. In view of the current global environmental challenges and social responsibility requirements, the motivation of this study is to provide an integrated transformation pathway for LMPSVs to achieve the goal of sustainable development and to contribute to the field of related disciplines. The methodology of this research adopts a combination of literature review and case study analysis, and the theoretical basis is mainly drawn from cutting-edge research in the fields of sustainable development, corporate social responsibility (CSR) and environmental management. Then, by analyzing successful transformation cases in China, we extract data and information to explore the application and effectiveness of these strategies in practice. The results of the study show that by implementing ESGI-based transformation strategy, LMPSVs can not only make significant progress in terms of environmental protection, social responsibility, and governance structure, but also drive long-term corporate growth and competitiveness through innovation. Specifically, these results are realized in terms of increased efficiency in energy use, improved waste management, community involvement and increased stakeholder satisfaction. The study concludes by emphasizing that the SSD-based ESGI Transformation Strategic framework provides a sustainable pathway for LMPSVs. In the future, the extension of this transformation strategy will help a wider range of industry sectors to achieve sustainable development goals, and has wide application potential and far-reaching social significance.

Multilingual classrooms are becoming more common worldwide due to increasing mobility. Teaching foreign languages using the mother tongue in multilingual classrooms has become problematic; some of the significant concerns in Japanese language acquisition – such as the high contextuality of the language, vocabulary and kanji learning – make the direct teaching method confusing for many students, especially at the beginner and elementary levels. This article provides the preliminary results of a study carried out as a component of a more extensive empirical research project on instructional languages in classrooms teaching Japanese as a foreign language. It aims to gather, analyse and synthesise data from a survey conducted at a supranational level. The results of the first two sections of a questionnaire containing closed and open-ended questions were used for a quantitative analysis of the profile of Japanese language instructors with a focus on finding possible connections. The wide geographic distribution of the respondents (274 teachers from fifty-seven countries and regions) made it possible to collect data from a more representative sample and draw meaningful conclusions about the spread of multilingual classrooms that would be impossible in smaller-scale research. The study’s primary results show the proportion of multilingual classrooms among countries in different regions and across different educational stages, the distribution of Japanese language instructors in various educational stages depending on the highest level of formal education attained, and the proportion of part-time instructors working in different academic institutions.

Intestinal parasitic infections pose a significant public health challenge in Northern Nigeria, with prevalence rates ranging from 20% to 70%. Traditional diagnostic methods, primarily microscopic examination of stool samples, face limitations such as low sensitivity and high costs. This research addresses these challenges by proposing an Artificial Intelligence (AI)-based platform for the identification and counting of intestinal parasites. A total of 651 samples were collected from the 7 Northern State of Nigeria along with questionnaire collecting data on demographic, socio-economic, hygiene habits and environmental factors. Leveraging the You Only Look Once (YOLO) V8 model, trained on a dataset of 360 pre-processed and 467 annotated images, the AI model demonstrated promising performance metrics. Information-Theory-Based approaches including (CIFE, CMIM, DISR and ICAP) were used on various machine learning models (Naïve Bayes, Random Forest, Support Vector Machine and Decision Tree) to analyse the risk factors associated with the parasitic disease. The precision-recall curve, average precision, mean average precision, and F1 score indicated reliable detection and classification across various parasite classes. The accuracy (97%) and AUC (99%) scores shows that CIFE with Random Forest has the best performance indicating the significant risk factors associated with the parasitic diseases. The model exhibited a well-balanced trade-off between precision and recall, showcasing its potential as a cost-effective and accessible tool for improving the diagnosis and treatment of intestinal parasitic infections in resource-limited settings.

Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

We are losing love. By studying porn movies to understand love, I discovered that love originally comes from the body, from positive emotions and vibrations of the wonderful body, from the heart and all other parts of the body, such as sexual organs. António Damásio made Descartes’ error by postulating that feelings increase their power from homeostasis (mechanisms of life regu-lation from bacteria to humans). He made this mistake unconsciously because many people un-consciously have a very bad opinion of sexual organs. We consider them ugly because they come from the prehistoric period. I have combined António and Hanna Damásio’s work (body emotions, thinking and language). I discovered that porn actors do not talk during sex, and this is striking. Porn actors mirror what happens in society. This means that people come from prehistory, do not talk during sex, and still unconsciously behave like primitive animals during sexual intercourse; we do not respect the body sufficiently during sex. Therefore, love, which comes from the body, is smothered and buried. We must very delicately talk to the wonderful, delicious and respectful body to wake up love feelings, body emotions and vibrations during sex. We must invent talking movies with porn films. Language of positive emotions associated with the language of wonderful and delicious body will warm love feelings and will give envy to love through sexual intercourse because António Damásio discovered that emotions are social.

Domestic crime, conflict, and instability pose a significant threat to many contemporary governments. These challenges have proven to be particularly acute within modern-day Mexico. While there have been significant developments in predicting intrastate armed and electoral conflict in various contemporary settings, such efforts have thus far been limited in their use of spatial as well as temporal correlations, as well as in the features they have consid- ered. Machine learning, especially deep learning, has been proven to be highly effective in predicting future conflicts using word embeddings in Convolutional Neural Networks (CNN) but lacks the spatial structure and, due to the black box nature, cannot explain the importance of predictors. We develop a novel methodology using machine learning that can accurately classify future anti-government violence in Mexico. We further demonstrate that our approach can identify important leading predictors of such violence. This can help policymakers make informed decisions and can also help governments and NGOs better allocate security and humanitarian resources, which could prove beneficial in tackling this problem. Using a variety of political event aggregations from the ICEWS database alongside other textual and demographic features, we trained various classical machine learning algorithms, including but not limited to Logistic Regression, Random Forest, XGBoost, and a Voting classifier. We considered a mix of CNN + Long Short Term Memory (LSTM) networks to decode the spatial and temporal relationship in the data. The performance of all the black box deep learning models was not at par with the classical machine learning models. We also evaluated the temporal relationships in the data to identify important predictors that fuel anti-government violence along with their directions using Shapley additive values. The voting classifier, utilizing a subset of features derived from LASSO across 100 simulations, consistently surpasses alternative models in performance and demonstrates efficacy in accu- rately classifying future anti-government conflicts. Notably, Random Forest feature importance indicates that some features, including but not limited to homicides, accidents, material conflicts, and positive worded citizen information sentiments emerge as pivotal predictors in the classification of anti-government conflicts. Finally, we conclude the research by analysing the spatial structure of the data using Moran’s I index extended version for spatiotemporal data to identify the global spatial dependency and local clusters followed by modelling the data spatially and evaluating the same using Gaussian Process Boost(GPBoost). The global spatial autocorrelation is minimal, characterized by local- ized conflicts cluster within the region. Furthermore, in Phase 3, the Voting Classifier method demonstrates superior performance over GPBoost, leading to the inference that no substantial spatial dependency exists among the various locations.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

We demonstrate that multiple well-known metrics, such as the Schwarzschild metric and the extremal solution of the Reissner-Nordstr ̈om metric, can be expressed in what we will call thermodynamic form. These formulations appear to be valid for all Rs = ct growing black holes and, therefore, also within the framework of Rh = ct growing black hole cosmology. However, the metrics can also be applied to non-black hole gravitational objects as long as one calculates the CMB and Hawking temperature of the hypothetical black hole from the gravitational mass.

The ordinary 3D wave equation for nondissipative, homogeneous, isotropic media admits solutions where the point sources are permitted to move, but it does not admit solutions where the receiver is allowed to move. To overcome this limitation, the new wave equation is derived, permitting both the receiver and the source to move. This new wave equation is a generalization of the standard wave equation, and it reduces to the standard wave equation when the receiver is at rest. To derive this new wave equation, we first mathematically define a diverging spherical wave caused by the stationary point source. From this purely mathematical definition, the wave equation for the stationary source and the moving receiver is derived together with the corresponding free-space Green's function. Utilizing the derived Green's function, it was shown that this new wave equation also permits the solutions where both the receiver and the source are permitted to move. In conclusion, this paper demonstrates that, instead of an ordinary wave equation, the wave equation for the moving source and the moving receiver governs the waves emitted by the moving point sources and received by the moving receivers.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

Friction stir welding (FSW) is a solid state welding process for joining metallic alloys and dissimilar metals. It has emerged as an alternative technology for welding high strength alloys that are difficult to join with conventional techniques. FSW is used to produce products with better mechanical properties. Now a days aluminum alloys have been widely used in several industrial applications such as aerospace, marine, automobile and commercial applications due to their light weight structure, better mechanical properties and high corrosion resistance.In this work, three welding parameters such as spindle speed, welding speed and plunge depth were considered for friction stir welding. FSW was carried out between dissimilar aluminum alloy plates (AA6061 and AA 8011) to produce butt joint.A Box-Behnken design with three factors and three levels was chosen to minimize the number of experimental conditions .The tensile strength and hardness of the welded regions were evaluated. The optimum level settings and the major parameters that influence the joint strength were obtained by Box-Behnken design.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

The future index prices are viewed as a critical issue for any trader and investor. For this craving, various models have shown up in the literature. The Geometric Brownian motion (GBM) is one of the popular models. This work examines four types of GBM as per the presence of memory or kind of volatility. These models include classical GBM with memoryless and constant volatility assumptions, SVGBM with memoryless and stochastic volatility assumption, GFBM with memory and constant volatility assumption, and SVGFBM with memory and stochastic volatility assumption. These models are utilized in an empirical study to forecast the future index price of Energy Sector in the Saudi Stock Exchange Market. The assessment was led by utilizing two error standards, mean square error (MSE) and mean absolute percentage error (MAPE). The outcomes showed that the SVGFBM occupies the highest level of accuracy according to smallest values of MSE and MAPE. While the accuracy of GBM come in the tail of the list models under study. These results have affirmed the positive affection of combining memory and stochastic volatility assumption into the GBM model, which agreed findings of numerous earlier works. Furthermore, the findings showed the GFBM models are more accurate than GBM models regardless of the type of volatility. While, under the same type of memory, the models with stochastic volatility assumption are more accurate than the corresponding models of constant volatility assumption. In general, all models considered in this work uncovered high accuracy through the value of MAPE ≤ 10%. This indicates of the ability of applying these models in a real financial environment. Through this empirical study, we can say that the Energy Sector in Saudi Arabia is predictable and stable and afterward we urge financial investors and stockholder to trade and invest in this sector.

The escalating levels of atmospheric carbon dioxide (CO₂) due to anthropogenic activities have raised significant concerns regarding their far-reaching consequences, including potential impacts on human brain function. This study employs Agent-Based Modeling (ABM) and a comprehensive literature review to comprehensively examine the effects of varying atmospheric CO₂ concentrations on human brain activity. Historical and projected CO₂concentration data, along with neuroscientific insights, were integrated into the ABM framework to simulate brain activity responses under different CO₂ scenarios. The simulations revealed that elevated CO₂ levels disrupt neural activity and alter neurotransmitter profiles, indicating potential cognitive consequences. Sensitivity analysis emphasized the importance of accurate parameterization for robust simulations. The findings underscore the urgent need to address global CO₂ emissions to preserve cognitive health. Further research is essential to validate and refine the model, incorporating additional factors for a comprehensive understanding of the cognitive repercussions of rising CO₂ levels, crucial for informed policy-making and public awareness campaigns.

In the dynamic landscape of the telecommunications industry, understanding and mitigating customer churn is paramount for maintaining competitive advantage and sustaining revenue streams. This comprehensive literature review delves into the intricacies of customer churn prediction, a crucial aspect in fortifying the bond between telecom businesses and their customers. The review methodically analyzes 11 articles published between 2000 and March 2024, spotlighting the strategic role of Customer Relationship Management and the prevalence of high churn rates that necessitate a shift from customer acquisition to retention strategies. Furthermore, the review navigates through the challenges inherent in churn prediction, including the complexities of managing large, imbalanced, and noisy datasets and the intricacies involved in model selection and optimization. Despite these challenges, the paper highlights the superior capability of machine learning techniques in handling complex datasets to provide accurate predictions, albeit acknowledging their practical complexities. The main aim of the study is to provide an overview, serving as a knowledge base for researchers interested in machine learning techniques within the realm of telecommunications.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

Sorghum grain processing can improve the nutritional content by promoting dietary properties that contribute to food security and economic development. The quality, nutritional content, and processing properties of sorghum bicolor grain can greatly affected by the inbred line races and variance in pericarp colour.The current study assessed the influence of the Husking Fraction Time Units (HFTU) process, which employed set time units per second (S), on the variation in the nutritional profile of fifty-one inbred line sorghum varieties based on distinct pericarp colours. When the assessment of the nutritional profile was involved: dry matter, total protein besides, namely mineral (P, K, S, Ca, Mg, Na, Fe, Zn, and Mn). The variety groups showed a significance value of (P < 0.05), indicating the study hypothesis's truth.The results demonstrated substantial impacts implied by the Husking Fraction Time Unit (HFTU) technique. This occurrence was noted when the dry matter percentage was increased in the husked products, specifically the endosperm (grits) and bran. The protein percentage redistributed by 19.2% compared to the whole grain and bran content. In comparison, the ratio of N/S was 14:1 in the S. bicolor and 12:1 in the kafirin in the bran part. Moreover, a strong correlation was observed among the examined minerals of S.bicolor and kafirin, such as the correlation between Ca: P, K: Na, and Fe: Zn attributed 80 (S) time unit, with correlation coefficients of R = 0.784 and R = 0.586, R= 517, R= 0.884, R= 0.745, and R = 0.893, respectively. At the same time, the 80 (S) time unit showed a significant effect on the colour property profile.The study results could benefit breeders and nutrition specialists in developing genotypes and processing sorghum grains, promoting research, and aiding several industrial sectors owing to the grain's adaptability and nutritional properties.

In this paper is proposed an analytical technique which can be used to obtain the forced response of a cantilevered tube conveying fluid. Considering the pipe subjected to an arbitrary harmonic force either distributed or concentrated, an analytical solution is found using Green’s function method. The solution obtained of the closed form satisfies the differential equations in a classical sense. The presented method giving the exact solutions is more precise than the classical eigenfunction expansion or Galerkin’s method with no need to the eigenfunctions or eigenvalues.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

Abstract—Hydraulic switching actuators are high efficiency, fast response, and low cost solutions for hydraulic control systems. One of the challenging problems is throttling losses during valve transitions. Previously the authors proposed a zero-flowrate switching method to reduce throttling energy loss of the switching valve, where a hydraulic resonator is applied to make the flowrates through the lines approaching zero before the valves are switched off. The major challenge of this approach is fast switching valves whose transition times are less than 2 ms. In this paper, an improved zero-flowrate switching method is presented. It utilizes the capacity with independent inlet/outlet ports to regulate flowrates through the lines. Models of capacity applied in a simple line with different pressure signals are developed to explore characteristics of the capacity, based on which a complete actuation system is developed. In the complete model, resistance and inductance are optimized to achieve desired flowrate response. The improved zero-flowrate switching method reduces throttling energy losses by 99.945% compared to a hard switching system. The simulation results demonstrated that the improved zero-flowrate switching method performs as expected in the design condition. A capacity with proper volume is able to regulate flowrates through all the lines to zero, with the help of appropriate resistance and inductance. Compared to previous zero-flowrate switching method, the novel strategy allows slower switching valves applied in hydraulic actuation systems and achieves better efficiency performance. This research paves a new avenue for reducing throttling energy losses and improves system efficiency in hydraulic switching actuators, as well as most of the hydraulic switch-mode circuits.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

The global textile sector, pivotal to economic development, significantly contributes to environmental degradation, prompting a shift towards sustainable raw material sources. Embracing circular economy principles, this industry is exploring the valorization of agricultural by-products. This study introduces an innovative approach to repurposing mango waste into valuable textile fibers, a byproduct of the fruit processing industry, predominantly generated during juice and jam production. The focus is on the lignocellulosic constituents of mango waste, specifically the peel, seed, and fibrous material, traditionally considered as refuse. Previous research has predominantly utilized mango peel in pectin extraction for food applications, whereas the potential of seed and fibrous content remains underexplored. This investigation endeavors to transform these fibrous by-products into high-value materials suitable for textile manufacturing. The process involved washing, drying, and comprehensive physicochemical characterization of mango fibers, emphasizing lignin quantification, revealing a composition of 12.2% lignin. An experimental design was employed to elucidate the impact of variables such as liquid-to-solid ratio, reaction duration, and sodium hydroxide concentration on lignin dissolution through alkaline hydrolysis. Optimal conditions—10% NaOH concentration, 30 mL/g liquid-to-solid ratio over six hours—achieved an 83% reduction in lignin content. The resulting fibers exhibited properties akin to conventional natural fibers, including a favorable aspect ratio indicative of their suitability for textile applications. A subsequent softening process using propylene glycol enhanced the fibers' spinability, producing a durable, textured fabric ideal for eco-conscious fashion applications, including bags, footwear, and accessories. This research demonstrates the feasibility of converting mango waste into a textile-worthy material and underscores the importance of waste revalorization in promoting sustainability within the circular economy framework.

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

Artificial intelligence (AI) has emerged as a powerful tool for addressing the challenges posed by climate change and their impact on public health. By leveraging its capacity to analyze and predict climatic patterns, AI offers opportunities to enhance resource management and develop effective strategies for climate change mitigation. Moreover, AI can contribute to generating sustainable solutions that address the complex and interconnected nature of climate change. For example, AI can enable the optimization of energy consumption and facilitate the integration of renewable energy sources into existing systems. It can also support the development of climate models that provide timely and accurate predictions, enabling policymakers to implement proactive measures for disaster preparedness and response. Furthermore, AI-powered disease surveillance and mitigation techniques can improve public health outcomes by identifying patterns and trends in the spread of diseases in relation to climatic factors.However, the widespread adoption of AI-based solutions is not without challenges. Ethical concerns surrounding privacy and data ownership must be addressed, as the use of AI requires access to large datasets, raising potential privacy risks. Technical constraints, such as limited computational power and the need for sophisticated algorithms, also pose obstacles to the implementation of AI in climate change mitigation strategies. Furthermore, issues related to the accessibility and affordability of AI technologies must be resolved to ensure equitable distribution and maximize its potential impact on public health.To fully harness the power of AI in addressing climate change and improving public health outcomes, it is crucial to promote innovation, multidisciplinary collaboration, and open data science. Innovation can drive the development of new AI algorithms and technologies specifically tailored to address climate change challenges. Multidisciplinary approaches that bring together experts from diverse fields, including climate science, public health, and computer science, can foster a holistic understanding of complex systems and enable the design of comprehensive solutions. Finally, open data science practices, such as sharing data and algorithms, can facilitate collaboration and accelerate progress in mitigating climate change and its public health impacts.In conclusion, AI offers promising opportunities for effectively addressing climate change and its impact on public health. However, to fully realize its potential, it is essential to tackle ethical and privacy concerns, overcome technical constraints, and ensure accessibility and affordability. By promoting innovation, multidisciplinary collaboration, and open data science, we can unlock the transformative power of AI in mitigating climate change and improving public health outcomes.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

The purpose of this project is to develop and build an extensible fixture. This fixture is ideal to milling, drilling, and shaping operations. Jigs and fittings are often the most cost-effective methods of mass fabricating a component. As a result, jigs and fittings are used and play a vital part in the mass production system. These are specialist work holding and tool-guiding devices. The quality of jigs and fixtures used in a process has a substantial impact on its performance. A fixture is distinctive because it is meant to fit a given area or shape. The basic purpose of a fixture is to find and, in certain instances, hold a workpiece throughout an operation. A jig differs from a fixture in that it leads the tool to the right position or movement during an operation, in addition to locating and supporting the workpiece. When a key is reproduced, the original key serves as a base for the path reader, which regulates the tool's movement to construct the duplicate key. In this situation, a CWC machine's route reader works as a jig, with the original being referred to as the template. Sometimes the template and jig refer to the same part of a production system.

The objectives of this paper are to investigate the tradeoffs between a physically constrained neural network and a deep, convolutional neural network and to design a combined ML approach ("VarioCNN"). Our solution is provided in the framework of a cyberinfrastructure that includes a newly designed ML software, GEOCLASS-image, modern high-resolution satellite image data sets (Maxar WorldView data) and instructions/descriptions that may facilitate solving similar spatial classification problems. Combining the advantages of the physically-driven connectionist-geostatistical classification method with those of an efficient CNN, VarioCNN provides a means for rapid and efficient extraction of complex geophysical information from submeter resolution satellite imagery. A retraining loop overcomes the difficulties of creating a labeled training data set. Computational analyses and developments are centered on a specific, but generalizable, geophysical problem: The classification of crevasse types that form during the surge of a glacier system. A surge is a glacial catastrophe, an acceleration of a glacier to typically 100-200 times its normal velocity. GEOCLASS-image is applied to study the current (2016-2024) surge in the Negribreen Glacier System, Svalbard. The geophysical result is a description of the structural evolution and expansion of the surge, based on crevasse types that capture ice deformation in six simplified classes.

We discuss three key points: defining mathematically the notions of phase, symmetry breaking, topological defects and their stability in a formal language of homotopy theory and fiber bundle formalism; postulating and proving two theorems for successive symmetry breaking scenarios in condensed matter physics and cosmology, and demonstrating application of theorems to superfluid Helium 3 and Kibble-Lazarides-Shafi (KLS) walls, supporting and mathematically justifying the results of [Volovik, 2020].

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes are located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes are expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. Hox clusters are irreversibly elongated along the force direction. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can ‘explain’ this Empirical Rule. In a spontaneous mutation where the cluster fastening is dismantled, a weak pulling force automatically shifts the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of Temporal Collinearity in Drosophila.

In this article, we investigate both the Schrödinger and continuity equations in the presence of nonlocal potential that arising from electron-electron interaction and local one in the context of minimal uncertainty in momentum within commutative and noncommutative frameworks. Furthermore, the Frahn–Lemmer potential type is used. Interestingly, the combined effects of both the phase-space noncommutativity and nonlocality on the current density while considering a minimal uncertainty in momentum are examined. We find that the current density, as conventionally defined, does not fulfil the condition of current conservation, thus, a new definition of the current density that encompasses the aforementioned contributions is given. Thereafter, it is shown that the computed current using the new definition of the current density satisfies the current conservation. Noting that using both the $★$product and linear Bopp-Shift, the noncommutativity is inserted.

The Jakarta LARP community, established in March 2020 and primarily active in Gelora Bung Karno, fosters inclusivity, diversity, and physical role-playing activities. It adheres to a policy of excluding ultra-nationalist ideologies and integrates new members despite language barriers. Bruhn (2011) defines this kind of community sharing the same goals, values, and lifestyles, while McMillan & Chavis (1986) outline four aspects of the sense of community.The research discovered that communities endure by utilizing solidarity built on the basis of their peculiarities. This study employed ethnographic methods alongside grounded research to identify the community's culture and their efforts to sustain and utilize it as community solidarity.

Amidst the challenges posed by the COVID-19 crisis, marked variations in individuals' resilience and vulnerability have emerged. This eight-month longitudinal study engaged 535 community adults (58% female, M_age = 43.97) to explore the nuanced aspects of coping and personal growth during the challenging period. Grounded in Self-Determination Theory, the research examines the influence of autonomy support from close others—manifested through active listening and providing choices—on psychological need satisfaction (i.e., autonomy, competence, and relatedness), integrative regulation of emotions; posttraumatic growth; and subjective well-being (positive affect and life satisfaction). Structural equation modeling revealed that, over time, the experience of psychological need satisfaction was intricately related to integrative regulation, posttraumatic growth, positive affect, and life satisfaction. Notably, the impact was partially mediated by autonomy support. These findings shed light on the pivotal role that autonomy supported relationships play in fostering personal growth and meaning making during life's difficult junctures. The study underscores the practical significance of purposeful support from close others and paves the way for future research endeavors.

Throughout this paper the impact of anxiety on adolescent athlete’s is highlighted through analyzing neurological and psychological aspects involved in sports performance. The neuroanatomy and neuropsychology of the human brain plays a major role in developing athlete’s that has only begun to be analyzed within recent years. Especially in young athletes, there are numerous factors that affect performance on the field that originate from the environment and training the adolescent athlete is involved in. Sports performance is viewed as a major physical factor such as training and lifting weights, however the psychological aspect of sports performance often goes unnoticed. Athletes can begin to develop mental fatigue and anxiety which inevitably can decrease their ability to perform. The athlete’s internal suffering begins to go unnoticed, as the only tangible factor is watching their performance decrease. This causes the athlete to push themselves further in training resulting in greater mental fatigue. This paper emphasizes the numerous factors neurologically that play a role in athletic performance which should be focused on in adolescent athletes as they navigate the challenges and competition that are apparent within athletics. It is critical to understand the processes and hormonal changes the body undergoes with training and playing a sport, this information can change the way adolescent sports are approached and advanced.

This study explored what motivates university counselors. By analyzing various factors like personal values and work environment, they found counselors experience greater career satisfaction when their work aligns with their own values and societal impact, and when they receive recognition and opportunities for growth. Universities can utilize these findings to create a more supportive environment for counselors by highlighting their impact, offering development opportunities, and fostering a positive work culture. This can ultimately lead to a more motivated and effective counseling team, benefiting both the counselors and the students they serve.

Recently, Gohar et al. introduced a novel, local, and well-behaved fractional calculus. It possesses all the classical properties, and Its locality imposes simplicity and accuracy in modeling fractional order systems. In this article, we further develop the definitions and extend the classical properties of Gohar fractional calculus to address some of the open problems in Calculus. The fractional Gronwall's integral inequality, Taylor power series expansion, and Laplace transform are defined and applied to overcome some of the limitations in the classical integer-order calculus. The fractional Laplace transform is applied to solve Bernoulli-type logistic and Bertalanffy nonlinear fractional differential equations, and the criteria under which it can be applied to solve linear differential equations are investigated.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

The work contains a detailed analysis of the electromagnetic field originating from a point source placed above the layered structure.The surface impedance of the multilayer dielectric structure was determined. Based on the boundary conditions, a method for determining the surface impedance of a layered structure with a perfectly conductive screen and or a magnetic screen is presented. The resonance conditions and the conditions for the excitation of surface waves are derived. The integral expression defining the generalized impedance was analyzed with a view to adapting it to numerical implementation. This allowed the development of a computer program based on which calculations were made of the effect of excitation of waves on multilayer dielectric substrates.

This study investigated the relationship between aluminum adjuvant vaccines and the prevalence of 4 childhood diseases (Autism, Allergies, Asthma, ADD/ADHD) using data from the 2020-2021 National Survey of Children's Health (NSCH) [1] and the Centers for Disease Control National Immunization Survey (CDC NIS) [2]. The study found an association with aluminum adjuvant dosage and the prevalence of each disease studied (Autism, Allergies, Asthma, ADD/ADHD) through a weighted regression analysis of disease prevalence against the summed likelihood of aluminum adjuvant vaccine uptake.

Prostate cancer is the second most frequent malignancy (after lung cancer) in men worldwide. Prostate tissue biopsies are usually graded using scores according to the Gleason grading system. This Gleason score is the most popular prognostic marker that reveals the potential aggressiveness of the disease. However, inter-observer variability in rating by human assessors is a major limiting factor. Such variability could lead to missing a severe case or suggesting unnecessary treatments. This study explores the discriminative ability of artificial intelligence (deep learning models) for Gleason score assessment. The study was designed to use whole-slide images of digitized H&E-stained biopsies of prostate tissues to automate the grading process and provide a remotely accessible clinical decision support system. Custom convolutional neural network architectures were trained on 10,616 images of prostate tissues. Gaussian filters were applied to pre-process the images and improve model performance. Transfer learning was applied to train eight machine learning architectures namely: Xception, VGG16 & 19, ResNet101, MobileNet, DenseNet121, EfficientNetB5 & B7. Efficient NetB7 had the best performance 85.2% compared with ground-truth classification by experts. Performance improves as more data is available. The model was deployed and hosted as a web application API on Google cloud service to ensure remote access. Tissue biopsy images can be uploaded and the corresponding Gleason score recovered immediately. This system reduces diagnostics turnaround time, increase throughput, and compensate for limited skills, especially in low resource settings.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

Analysis of complex DNA mixtures is limited by the selected genetic markers characterized and assay technology. Small panels of short tandem repeats (STRs) are the current standards in most countries. Extension of STRs with hundreds of single nucleotide polymorphisms (SNPs) is now commercially available. The current set of extension SNPs focus on phenotypic and biogeographic ancestry informative SNPs. Larger panels with thousands of SNPs have been developed that can identify up to 10 contributors to forensic DNA samples. Herein, multiple sets of SNPs were selected with the focus of increasing the upper limit of detectable contributors. Larger SNP panel sets with lower minor allele frequency (MAF) alleles can detect large numbers of contributors to in silico mixtures of randomly selected profiles from the 1,000 Genomes project. These results provide a path to enable characterization of complex DNA mixtures that are currently impossible to analyse.

In many countries, increasing concern for animal welfare is driving retailer commitments and government legislation that aim to improve the lives of farmed fish. One aspect of fish welfare involves stunning fish prior to slaughter. The feasibility of stunning depends on the species of fish and physical farm characteristics. In this article, we provide an overview of stunning before slaughter in European sea bass and sea bream aquaculture, one of the largest finfish farming industries in the developed world that does not yet stun most of its production. Sea bass and sea bream stunning necessitates the use of electrical stunning equipment aboard harvest vessels, often a significant distance from the shoreline; this presents an interesting engineering and policy challenge. Together, Türkiye, Greece, Spain, and Italy produced over 400,000 t of sea bass and sea bream in 2020. In Türkiye and Greece, farms are numerous and located very close to the shoreline. In Spain and Italy, farms are few and located far from the shoreline. The highest average production is found in farms from Türkiye (1,000 t) and Spain (1,300 t, and lower average production is found in Greece (300 t) and Italy (350 t). Producer progress towards the installation of electrical stunning appears comparatively well-developed for Türkiye, Spain, and Greece, though we emphasise that producers and other stakeholders require continued support to realise this opportunity. Producers in Italy appear slower to make progress on this aspect of animal welfare and may require additional support.

This research challenges the traditional perspective on consumer behavior, which focuses on external factors shaping the sequential stages of decision-making. Instead, it proposes a paradigm shift by treating the decision-making process itself as an independent variable, exploring its impact on various outcomes like purchasing behavior, brand loyalty, and post-purchase satisfaction. This novel approach offers deeper insights into the intricacies of consumer behavior, particularly in the digital age. By uncovering the reciprocal relationships between the decision-making process and other variables, the research provides a more nuanced understanding of how consumers navigate today's complex landscape. It further delves into how variations in the decision-making process across diverse consumer groups influence various outcomes, recognizing the unique characteristics and needs of different demographics. The research also acknowledges the interplay of psychological, social, and contextual factors that shape both the decision-making process and its downstream effects, offering a comprehensive understanding of the multifaceted influences on consumer behavior. Ultimately, by studying the decision-making process as an independent variable, this research aims to equip businesses and researchers with valuable insights, enabling them to better navigate the ever-evolving world of consumer behavior.

We introduce the linear subgroup of volume-preserving diffeomorphism as the underlying symmetry to construct an action within the effective field theory framework and the Schwinger-Keldish formalism. The formulated action is posited to effectively incorporate dissipative effects into the Navier-Stokes equations.

The hard open problem of finding the lower bound for the Fokker Planck Kolmogorov’s time-dependent controller parameter probability density function is addressed for the first time in literature in this work. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to multi-interdisciplinary fields of human knowledge, and beyond. So, this by default adds more taste and credibility to this study. Concluding thoughts are included at the end of the work along with a difficult outstanding problem and the direction of future work.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

This study focuses on examining various approaches for Tensor Decompositions (TDs) and their potential applications in satellite imaging (SI) and deep learning (DL). The research highlights how these decompositions can contribute to the advancement of SI and DL, providing valuable insights for future utilization of TDs in research. It explores how these techniques contribute to the advancement of SI and DL methods, providing insights into their potential applications and suggesting future research directions. The study aims to enhance the use of TDs techniques to further advance research efforts in these fields. More importantly, the current investigation offers a thorough analysis of the potential advantages and reasons for employing TDs techniques in different domains, including satellite imaging and deep learning. The aim is to enhance research outcomes by utilizing TDs. The review also identifies unresolved issues and proposes future directions for further investigation in this field. Fundamentally, these proposed open problems will open new grounds to the research community to articulate, innovate, and provide more real-life applications to improve the current state of the art by delving into a wider vision for a higher-level performance of both satellite imaging (SI) and deep learning (DL). Looking at the bigger scenario, this also suggests that TDs could be potentially employed to revolutionize existing machine learning technologies as well as the current space AI industry.

This work is the first in literature to tackle the difficult open problem of determining the upper bound and threshold theorem for the TDCDP (time-dependent controller parameter) of the (Fokker Planck Kolmogorov) probability density function. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to information theory, graph theory, data science, finance, economics, and beyond. So, this by default adds more taste and credibility to this study. This leads by nature to introducing a different flavor to this ground-breaking research by highlighting the impact of Fokker Planck Kolmogorov(FPK) to revolutionize crypocurrency,which have received its name because it uses encryption to verify transactions, a new debatable digital payment system that doesn't rely on banks to verify transactions. It’s a peer-to-peer system that can enable anyone anywhere to send and receive payments. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

Introduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

This paper shows the firsts results of a methodological approach in which Remote Sensing technologies (Satellite imagery and LiDAR) combined with Least Cost Path algorithm on GIS are being tested like tools to overcome locally-based interpretations about populational patterns and communication routes during Flavian municipality in the Comarca de El Condado region. The identification of fourteen hypothetical communication routes between already known archaeological sites thanks to a recent archaeological prospection, and the confirmation of three sections of them and a new archaeological site demonstrate that the combined use of the aforementioned technics has a very useful to delve more deeply, more widely and at a variety of different scales into the relation between the twelve known/selected Early Roman Empire sites and the surrounding landscape in the right bank of Guadalén River. It is expected that, in next phases, this methodological approach will allow us to go deeper in analysing and understanding spatial distribution, exploitation, and interrelation between different Early Roman Empire sites, helping us to fill the aforementioned gaps in our understanding of the archaeological continuum in the region reducing time and costs.

This article is devoted to the problem of genetically coding of inherited cyclic structures in biological bodies, whose life activity is based on a great inherited set of mutually coordinated cyclic processes. The author puts forward and arguments the idea that the genetic coding system is capable of encoding inherited cyclic processes because it itself is a system of cyclic codes connected with Boolean algebra of logic. In other words, the physiological processes in question are cyclical because they are genetically encoded by cyclic codes. In support of this idea, the author presents a set of his results on the connection of the genetic coding system with cyclic Gray codes, which are one of many known types of cyclic codes. This opens up the possibility of using for modeling inherited cyclic biostructures those algebraic and logical theories and constructions that are associated with Gray codes and have long been used in engineering technologies: Karnaugh maps, Hilbert curve, Hadamard matrices, Walsh functions, dyadic analysis, etc. Additionally, the connections of these constructions with statistical rules of genomic DNAs and binary-genomic numbers are considered.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

This paper explores the views of a group of young men aged 16–18, studying towards a Level 1 diploma in music in the North East area of England. It uses the conceptualization of “social haunting” to focus our discussions about how Level 1 learners articulated their experiences in the context of their learning journeys and perceived marginalization. The research took place at a large Further Education (FE) college and included a series of five “research encounters” with the group of Level 1 learners. These encounters included a range of activities, resulting in a variety of data being collected, including several activity worksheets, structured and unstructured focus group interviews, and questionnaires. This paper focusses on the outcomes of a single research activity that focused on exploring the topic of marginalization. We present a discussion on social haunting as one of the emerging findings from this research encounter, outlining how the reality of the social and cultural legacy of the UK’s industrial past can shape today’s youth and their futures. We will talk about the young men’s views of marginalization, their school-to-work transitions, the formation of masculinity in post-industrial communities and the role of Further Education in it. The paper concludes by discussing some insights for practice and future research.

This study delves into the realm of potential therapeutics for breast cancer by conducting a comprehensive docking simulation and virtual screening analysis using Autodock Vina Algorithm. The focus based on the human epidermal growth factor receptor 2 (HER2), a key protein associated with various cancers, particularly in the context of breast cancer.The results reveal compelling insights into the binding interactions of several natural compounds and drugs with HER2. Notably, Acebilustat, Bemcentinib, and Amentoflavone exhibit outstanding binding energies, averaging around -10 kcal/mol, suggesting strong and favorable interactions with the HER2 target.These encouraging findings not only emphasize the potential biological significance of these compounds but also hint at their potential usefulness in fighting breast cancer.Their promising binding affinities with HER2 position them as potential candidates for further investigation and development as therapeutic agents against breast cancer.

Neisseria gonorrhoeae is a bacterium that causes the sexually transmitted infection gonorrhea. This study employed molecular docking simulations to investigate potential interactions between natural molecules and the Fe(3+) ions import ATP-binding protein fbpC in Neisseria gonorrhoeae FA 1090. Among the screened molecules, Hypericin exhibited a remarkable binding energy of approximately -13.2 kcal/mol, indicating a robust and favorable binding affinity with the target protein. This promising outcome suggests that Hypericin could serve as a potential candidate for further exploration as a therapeutic agent against Neisseria gonorrhoeae infections. However, it is imperative to emphasize that these in silico findings necessitate experimental validation through in vitro and in vivo studies to ascertain the actual efficacy and safety of Hypericin as a treatment option.

Abstract: Social media has become a vital tool in ensuring productivity among Undergraduates, as studies have shown an increased number of users globally. This study assessed the impact of social media usage on undergraduates’ academic performance and working memory. Participants from three different universities such as the University of Georgia (UG), Eastern European University (EEU), and Batumi State University (BSU) completed this study using online google forms. UG and EEU are in the capital city, and BSU is in Batumi City. The study questionnaires were approved by the institutional review board before the data collection. Descriptive analyses were assessed for all study populations, characteristics, frequencies, percentages, means, and standard deviations using Statistical Package for Social Science (SPSS Inc., Chicago, IL, version 25.0 for Windows) software. 41.3% were male students, as most of the participants were foreign students living and studying in Georgia. Male students had the risk of ‘conflict’ with families and friends because of social media. Female students are at increased risk of using social media as an ‘escape’ from negative feelings. 89.7% of students that perform physical activities, considering their academic workload had the risk of preoccupation complaints. 87.9% felt dissatisfied regularly because they wanted to spend more time on social media. Utilization of social media differed based on the characteristics of the participants such as age, gender, and geography. We observed the increase in prevalence of social media addiction, its effect on academic performance and working memory among undergraduate students.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

The bioindicator potential of seagrass ecosystems in coastal trace metal monitoring is low for tropical island ecosystems. This study evaluated the bioindicator potential of six seagrass species exposed to anthropogenic trace metal pollution in the Andaman and Nicobar Islands (ANI) of India. Sediment and seagrass biomass, samples were analyzed for trace metals (Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn) from four locations of ANI exposed to anthropogenic contamination. Geo accumulation Index values indicated moderate trace metal contamination in seagrass sediment. Seagrass trace metal accumulation from sediment was both species-specific and location- specific for ANI. Small seagrass species such as H. ovalis, H. beccarii and H. uninervis accumulated the maximum concentration of six trace metals (Cr, Cu, Fe, Ni, Pb, Zn) in their tissues compared to big seagrass species like T. hemprichii and E. acoroides of ANI. This study indicates leaves of small seagrass and roots of big seagrass species can serve as short- and long-term bioindicators respectively, of coastal trace metal contamination in tropical islands of ANI.

“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.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

This study delves into the intricate interplay between cosmology and gravity in dilaton-based models, enhancing our understanding. Exploring boundary theories coupled to gravity, we derive a four-dimensional effective theory from the cosmological constant. Dilaton gravity is then scrutinized, revealing elegant solutions and insights into brane embedding. The analysis extends to probe scalar fields, employing the WKB approximation in both conformal and non-conformal cases. In summary, this work contributes to a nuanced understanding of the complex relationship between cosmology and gravity in dilaton-based frameworks.

This study aimed to evaluate the discrepancies between genetic and visual coat color assignment in the Sarcidano Horse and to elucidate potential reasons. Individual DNA from 90 Sarcidano Horses was used for genetic assignment of coat color to explore the correspondence with individual forms containing phenotypical traits. The MC1R exon 1 and ASIP exon 3 have been genotyped and sequenced to obtain a picture of the coat color distribution in this breed. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data in relation to coat color emerged. From the genetic analysis, Chestnuts (n = 58) resulted the most common Sarcidano Horse (n = 58), followed by a quite large number of Blacks (n = 28) and a very small number of Bays (n = 4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Grays (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses that visually identified as Bays were genetically Blacks. This discrepancy, that could be due to a variety of individual and external factors, including age, time of year, living situation and dietary condition, suggesting the importance of accurate coat color identification to ensure adequate features registration and reliable prediction of offspring’s coat color.

Electromobility has gained significant attention in the auto- motive industry, with car manufacturers striving to improve the charging experience for their users. In this study, we compare multiple realistic charging strategies in order to quantify the benefits arising from better planning of charging sessions. We base our evaluation on electricity price data from three regions: Sweden (SE3 region), Germany (DE region), and Denmark (DK2 region). This data is obtained from the ENTSO-E Transparency Platform, covering the two full years 2021 and 2022. We enhance this dataset with commercial price forecasts from the company StormGeo and benchmark it against a naive forecasting method. The primary aim of our work is to compare how the strategies of varying levels of complexity perform across the three different countries in terms of minimizing energy costs for electric car users.