Developmental toxicity testing urgently requires the implementation of human relevant new approach methodologies (NAMs) that better recapitulate the peculiar nature of human physiology during pregnancy, especially the placenta and the maternal/fetal interface, which represent a key stage for the human lifelong health. Fit-for-purpose NAMs for the placental-fetal interface are desirable to improve the biological knowledge of environmental exposure at molecular level and to reduce the high cost, time and ethical impact of animal studies. This article reviews the state of the art on the available in vitro (placental, fetal and amniotic cell-based systems) and in silico NAMs of human relevance for developmental toxicity testing purposes, as well as of the available Adverse Outcome Pathways related to developmental toxicity. The OECD TG 414 for the identification and assessment of deleterious effects of prenatal exposure to chemicals on developing organisms will be discussed to delineate the regulatory context and to better debate what is missing and needed in the context of the developmental origins of health and disease hypothesis to significantly improve this sector. Starting from this analysis, the development of a novel human feto-placental organ-on-chip platform will be introduced as an innovative alternative tool for developmental toxicity testing, considering possible implementation and validation strategies to overcome the limitation of the current animal studies and NAMs available in regulatory toxicology and in the biomedical field.

Pandemic scenario has significantly changed several factors of life, including teaching, and learning at university. The development of suitable teaching materials to support university studies is mandatory to overcome distance learning difficulties and improve traditional teaching methodologies. This work explains a novel method for the preparation of teaching materials for medical sciences, but also plausible for other learning fields. An encephalon was extracted and prepared by using this methodology for teaching purposes. More than 200 students evaluated several factors of the material prepared this way, indicating a better understanding (up to 80%) of theoretical contents related to this human section, together with a high usability and good physical appearance

Current acceleration in digital innovations, the unexpected challenges in our social interactions, open access to virtualization, huge limitation in our physical spaces, and unpredictable changes in our old lifestyles - as originated from the COVID-19 global pandemic in 2020 - continue to provide us with a framework, rapidly updating under our eyes, of the modifications our world is undergoing by pursuing into the “new digital age”. Or, as many scholars say nowadays, into the new normal! These are shared and deep changes that, regardless of their permanence or temporariness in the time, concretely stress, ever more greatly, their “own” effects on how ideally a city should function. Forcing us to reflect on the real ability to achieve choices and visions for the future by taking vantage from the new digital platforms. In the pages of this article authors, through different eyes but sharing an early response to the matter of new Governance, explore the theme of a radical change of those already consolidated paradigms and, therefore, of the innovations that are transforming the way we understand our society and its technologic advancements, economics, and culture, as defined through dimensions of time and space. This article identifies a methodologic vision for acquiring a more democratic and participatory (inclusive) dimension in the newest configuration of contemporary cities, the new smart city, and in the possible innovations in reading the common sentiments and wishes through the new digitalized world. The analysis investigates how ICT is altering the meanings/ideas of “urban planning”, driving us toward a more effective “governance” through a citizen-centred digital approach. Indeed, city governance's success must be measured based on the “listening capacity” of the inhabitants and the facilities that we are capable to provide to citizens. “Sentiment Analysis” tool is tested as a useful tool to achieve these aims.

Urban green spaces provide a range of environmental and health benefits, which may become even more critical during times of crisis such as the current COVID-19 pandemic. However, with a radical shift in mobility, additional concerns over safety, and access temporarily restricted during the implementation of social distancing policies, the experience and use of urban green spaces may be reduced. This is particularly concerning for densely populated cities like New York, considered the first U.S. epicenter or vanguard of the outbreak. To better understand the impact of COVID-19 on the perception and use of urban green spaces, we conducted a social survey during the early months of the Covid-19 pandemic in New York City (May 13 - June 15, 2020). The results of the survey show respondents continued to use urban green spaces during the pandemic and consider them to be more important for mental and physical health than before the pandemic began. However, the study revealed a pattern of concerns residents have about green space accessibility and safety, and found key differences between the concerns and needs of different populations, suggesting a crucial role for inclusive decision-making, support for additional management strategies, and urban ecosystem governance that reflect the differential values, needs and concerns of communities across the City. As urban centers face looming budget cuts and reduced capacity, this study provides some empirical evidence to illustrate the value of urban green spaces as critical urban infrastructure, and may have implications for funding, policy, and management, of urban green spaces in NYC, with potential applications to other cities, particularly during times of crisis.

By using the new recently proposed extended rational methods, we set some solitary and multi wave solutions of the coupled Higgs system in the present study. Some new families of hyperbolic and trigonometric solutions of the coupled Higgs equations are successfully obtained. Some solutions are real as some are complex valued functions. Particular forms of some solutions derived by choice of some parameters are demonstrated in three dimensional spaces. The complex valued solutions are also depicted by plotting both real and complex component.

As Aotearoa-New Zealand faces increasing cyber threats, this paper comprehensively analyses the nation’s current cybersecurity landscape, revealing novel opportunities and challenges. Through an interdisciplinary approach, the study integrates social, cultural, and technological dimensions—providing a fresh perspective that has been underexplored in previous research. A key focus is integrating cultural values, particularly those of the indigenous Māori, into cybersecurity practices. This not only strengthens the effectiveness and trustworthiness of security measures but also fosters a more inclusive and resilient digital environment, demonstrating our deep respect for the unique contributions of Māori culture. Additionally, this paper introduces critical insights into the country's cybersecurity talent gap, with a special focus on the challenges of developing and retaining cybersecurity expertise in remote regions. Our study also uncovers underexplored opportunities for cross-sector collaboration between private enterprises, government agencies, and indigenous communities, promoting an inclusive and resilient approach to cybersecurity. By positioning Aotearoa-New Zealand as a potential leader in regional cybersecurity innovation, we provide forward-looking recommendations that leverage its distinctive cultural and technological strengths. This research contributes fresh insights to the global discourse on cybersecurity, offering practical strategies tailored to the specific needs of smaller nations.

Blood stream infections (BSI) due to carbapenem-resistant gram-negative bacilli (CR-GNB), especially Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo-β-lactamase (NDM) producers, are a major concern of public health, as they are associated with high morbidity and mortality. We conducted a single-center, retrospective, observational study at a tertiary-care, teaching Greek hospital, to determine the incidence, 30-day and overall, in-hospital, crude mortality, risk factors and efficacy of best available treatment options in patients with BSIs from KPC- or NDM-producing GR-GNB. During the one-year study period, from 1st January to 31st December 2023, we recorded 133 episodes of BSIs in 118 unique patients; 79 episodes were due to KPC-producing and 54 to NDM-producing CR-GNB. Our study showed relatively high incidence of BSIs by both KPC- and NDM-producing CR-GNB (0.49 and 0.31 episodes per 1000 patient-days respectively). We found high 30-day crude mortality rates for patients with BSIs due to KPC- producing CR-GNB (26.4 %), and NDM-producing CR-GNB (37%), while BSIs due to NDM-producing P. aeruginosa had the highest 30-day (47.1%) and overall (70.6%) in-hospital, crude mortality. Beta-lactam/beta-lactamase inhibitors as monotherapy or in combination with other active agents used to treat KPC-producing CR-GNB were associated with improved survival rates (p=0.009).

This study examines the recovery efforts at Gran Tarajal Harbor following a significant oil spill, employing innovative technologies. Initial response efforts were hampered by inadequate contingency plans and bureaucratic delays, underscoring the need for improved preparedness. Cleanup operations utilized advanced methods such as enhanced absorbent sponges, absorbent granulates, bioremediation with allochthonous species, and a combination of barriers and sponges. These technologies proved effective in minimizing environmental impact, reducing hydrocarbon concentrations in sediments from nearly 60,000 mg/kg to less than 1,600 mg/kg in seven months. Heavy metal analysis revealed lead and copper concentrations associated as well as with routine port activities, while mercury levels linked to the spill decreased over time. Tissue analysis indicated minimal contamination in local organisms, suggesting limited impact from the spill, and evaluation of the biological communities in sediments suggest an ecological recovery. Study underscores the importance of rapid response, advanced technologies, and detailed contingency plans tailored to each port. Despite the successful cleanup and ecosystem recovery, political and bureaucratic challenges remain significant obstacles to implementing these improved methods. The findings advocate for a re-evaluation of current oil spill response protocols to incorporate more effective, sustainable, and cost-efficient technologies, aligning with the principles of a circular economy.

In the current complex and uncertain macroeconomic situation, improving the inherent resilience of the new energy vehicle industry chain is the key to effectively addressing various risks and challenges, and achieving dynamic balance between high-quality industrial development and industrial chain security. Based on the basic concept of resilience and the actual situation of new energy vehicle industry chain development, this study constructs a comprehensive evaluation index system for the resilience of the new energy vehicle industry chain, which includes four dimensional first-level indicators of coping resistance, adaptive resilience, autonomous control and leading competitiveness. In addition, it is measured by combining the data related to the new energy vehicle industry chain in Changzhou City. Our study shows that the situation on the new energy vehicle industry chain is complicated, and the comprehensive evaluation index system is more favorable for evaluating its resilience level.

The article suggests a Value Proposition (VP) framework that enables the analysis of the beneficial impact of Artificial Intelligence (AI) resources and capabilities on specific VP development activities. To develop such a framework, we examined existing management research publications to identify and extract assertions that could be used as a source of actionable insights for new growth-oriented companies. The extracted assertions were assembled into a corpus of texts that were subjected to topic modelling analysis – a machine learning approach to natural language processing that is used to identify latent themes in large corpora of text documents. The topic modeling resulted in the identification of seven topics. Each topic is defined by a set of most frequent words co-occurring in a distinctive subset of texts that could be interpreted in terms of activities constituting the core elements of the VP framework. We then examined each activity in terms of its potential to be enhanced by employing AI resources and capabilities. The interpretation of the topic modeling results led to the identification of seven topics: 1) Value created; 2) Stakeholder value propositions; 3) Foreign market entry; 4) Customer base; 5) Continuous improvement; 6) cross-border operations; and 7) Company image. The uniqueness of the adopted topic modeling approach consists in the quality of the assertions and the interpretation of the seven topics as an activity framework, i.e. in its capacity to generate actionable insights for practitioners. The additional analysis suggests that there is a potential for AI to enhance emerging the four core elements of the VP framework: Value created, Stakeholder value propositions, Foreign market entry, and Customer base. More importantly, we found that the greatest number of assertions related to activities that could be enhanced by AI are part of the Customer base topic, i.e., the topic that is most directly related to the growth potential of the companies. In addition, the VP framework suggests that a company’s customer base growth is continuously enhanced through a positive loop enabled by activities focused on the Continuous improvement of the activities and the amount of Value created, the alignment of Stakeholder value propositions, and companies’ Foreign market entry. Thus, Foreign market entry appears as a factor that helps in understanding the beneficial impact of AI on the VP development of new growth-oriented companies.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 is the second-best FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody–drug conjugate (ADC) has been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year’s harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs, after the withdrawal of peginesatide from the market in 2013. Following the trends of recent years, two bispecific drugs have been authorized in 2023. As in preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Background: With continuous advances in next-generation sequencing (NGS), novel hepadnaviruses have been discovered in many species over the last 10 years. Methods: In this study, the cloud search and analysis of NGS data published in Nature by Edgar et al. was used as a basis to re-mine and reanalyze public NGS data for new hepadnaviruses. Results: Ultimately, at least 41 new species of hepadnaviruses were identified, including hepadnaviruses from the model animals hamster and mouse, frog hepadnavirus with pan-species infectivity, and diverse African cichlid hepadnaviruses that circulate within populations. Conclusions: The discovery of the new species of hepadnaviruses not only provides new clues for the study of the origin and evolution of hepadnaviruses, but also can be used to construct new hepadnavirus animal infection models, which will be helpful for the research of eradicative drugs for hepatitis B virus (HBV).

We firstly present two popular space discretization models of the Nonlinear Schrödinger Equation in dark solitons motion : the Direct-Discrete model and the Ablowitz-Ladik model. Applying the midpoint scheme to the space discretization models, we get two time-space discretization models: the Crank-Nicolson method and the New-Difference method. Secondly, we demonstrate that the solutions of the two space discretization models converge to the solution of the Nonlinear Schrödinger Equation. Also, we prove that the convergence order of the two time-space discretization models are O(h2+τ2) in discrete L2-norm error estimates. Finally, the numerical experiments agree well with the proven theoretical results.

Developing new energy is critical to China's green and low-carbon development. And the New Energy Demonstration City Policy (NEDCP) is a vital innovation policy that inspires the development of new energy. Is the NEDCP facilitating green and low-carbon development, if so, how? Employing unbalanced panel data from 2003 to 2017, the impact of NEDCP on green and low-carbon development was studied by using the "difference in difference" (DID) model. We find that this policy can take significantly role. After various robustness tests, our results are still valid. According to the heterogeneity analysis, non-resource and non-old industrial base cities have a greater positive impact from this policy. The mechanism analysis denotes that the positive policy effect works through upgrading the industrial structure and stimulating urban innovation. The substantial empirical evidence presented in this article supports the continued promotion and implementation of new energy demonstration cities.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

Burning woody biomass for energy is gaining attention due to environmental issues associated with fossil fuels and carbon emission. The carbon released from burning wood is absorbed by plants and is carbon neutral. The purpose of this study was to investigate the combustion characteristics (heat calorific values and ash contents) of three timbers: Araucaria cunninghamii, Instia bijuga and Pometia pinnata and recommend for fuelwood. The test samples were sawdust particles (treatment) and solid woods (control) extracted from the heartwoods. The sawdust particles were oven-dried, sieved and pelletized into pellets using a hand-held pelletizing device, thus, forming cylindrical dimension (volume 1178.57 mm3, oven dry density 0.0008 g/mm3). While the solid woods were cubed and oven-dried (volume 1000.00 mm3, oven dry density 0.001 g/mm3). Prior to combustion in a semi-automatic bomb calorimeter, 90 test specimens (15 replicates per treatment and control per species) were conditioned to 14 % moisture content (at temperature 105 ºC) and weighed to a constant (unit) mass (1.0 g). The heat energy outputs and ash residues (of treatments) were analyzed statistically. The results indicated variability in heat energy outputs and ash residues between test specimens of the three species. Comparatively, the treatment specimens of A. cunninghamii produced higher calorific value (18.546 kJ/g) than the control (18.376 kJ/g) whilst the treatment specimens of I. bijuga and P. pinnata generated lower heat calorific values (17.124 kJ/g and 18.822 kJ/g) than the control (18.415 kJ/g and 20.659 kJ/g), respectively. According to ash content analysis, A. cunninghamii generated higher residues (6.3%) followed by P. pinnata (4.5%) and I. bijuga (2.8%). The treatment specimens of the three species could not meet the standard heat energy requirement (20.0 kJ/g) and thus, were unsuitable for fuelwood. However, the control specimens of P. pinnata generated equivalent heat energy (20.659 kJ/g) and could be a potential fuelwood.

Rhoptry proteins of the RhopH complex (RhopH1/Clag, RhopH2 and RhopH3) participate in the formation of new permeability pathways for nutrient uptake in Plasmodium falciparum infected erythrocytes. RhopH proteins associate with the Maurer’s clefts (MC) during transport to the host cell membrane and interact with the cytoskeleton. However, the role of specific MC proteins facilitating rhoptry protein interaction and trafficking is unknown. The major interaction with MCs occurs with RhopH3. Dual roles ascribed to RhopH3 include functions in host cell invasion and formation of the plasmodial surface anion channel (PSAC). The topological orientation and organization of the RhopH3-MC membrane interaction in the host cell cytoplasm has not been described. In this study, we performed biochemical analysis to investigate the topology and trafficking of RhopH3 and Pf130 from the parasite to the erythrocyte cytoplasm using streptolysin O (SLO) permeabilization and protease treatment of infected erythrocytes. We investigated Pf130, a soluble protein previously identified by monoclonal antibodies and shown by immunoelectron microscopy (IEM) to be distributed underneath knobs and associated with the MC in infected erythrocytes. Pf130 is expressed early in the erythrocytic cycle and persists to the schizont stage. Immunofluorescence and confocal microscopy show that Pf130 is a resident MC protein due to its colocalization with the MC protein REX-1. Immunofluorescence assay (IFA) showed colocalization of Pf130 with RhopH3 in the cytoplasm of SLO permeabilized and trypsin treated infected erythrocytes. These novel findings show that both proteins were protected from protease digestion demonstrating that conformational changes are required to transport the RhopH proteins through association with the MC as integral membrane proteins.

Vaccination against HPV significantly reduced the incidence of HPV-related le-sions worldwide. Considering the increasingly younger age of patients in the gynaecological office and the resulting earlier sexual initiation and potentially contact with the HPV virus, doctors need to have tools to verify the diagnosis. Nowadays, women plan motherhood later, so it is necessary to consider whether sexual treatment in the form of, among others, LEEP-conization may increase the risk of premature birth or difficulty dilating the cervix during labour.For this reason, to avoid overtreatment of LSIL changes, methylation testing may be considered. In patients with histopathologically confirmed HSIL during biopsy and ultimately a lower diagnosis - i.e., LSIL or no signs of atypia - methylation turned out to be a useful tool. We performed Pap-smear, HPV genotyping, punch biopsy, LEEP-conization (if needed) and methylation test in 108 women admitted to the District Public Hospital in Poland. Women with a negative methylation test result were significantly more likely to be ultimately diagnosed with LSIL (p=0.013). This means that in 85.7% of patients with HSIL, major cervical surgery could have been avoided if methylation was negative. Methylation testing, as well as dual-staining and diagnostics detecting mRNA transcripts of highly oncogenic types of HPV, might be used in future in the diagnosis of pre-cancerous conditions, mainly of the cervix, and in HPV-dependent cervical cancer screening. The methylation test may also be used in the diagnosis and identification of lesions within the cervical canal, including those located deep within the frontal crypts, not visible even during a professional colposcopic evaluation of the cervix, as well as within the crypts of the palatine tonsils - in diagnostics of head and neck diseases.

Adaptive hyperactivity, characterized by increased activity levels and novelty-seeking traits without mood disorders, is prevalent among older adults in Sardinia's "blue zone," an area with high longevity. This study aims to evaluate the adaptive nature of hyperac-tivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among older adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 years from Sardinia's blue zone, recruited from the dermatology clinic at the University Hospital of Cagliari. Partici-pants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to na-tional averages (0.87%), without corresponding increases in dysregulated rhythms, de-pressive symptoms, or reduced quality of life. Younger elders (65-79 years) showed in-creased rhythm dysregulation (BSRS score: 20.64±7.02) compared to adults (17.40±6.09, p=0.040), but this trend was not observed in older elders (80+ years). No significant differ-ences were found in CH3SH and (CH3)2S levels between groups. Conclusions: Hyperactiv-ity observed in older adults from Sardinia's blue zone appears adaptive, not linked to so-cial rhythm dysregulation, depressive symptoms, or diminished quality of life, suggesting resilience factors that may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting fur-ther research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.

Studies of Phytophthora impacts in forests generally focus on individual species without recogni-tion that Phytophthora occur in multispecies communities. We investigated community structure of Phytophthora species in the rhizosphere of Agathis australis (kauri) in Te Wao Nui o Tiriwa / Waitākere Ranges, New Zealand, in the context of kauri dieback disease expression. Soil sampling and tree health monitoring was conducted on 767 randomly selected mature kauri trees. Phy-tophthora species were detected using both soil baiting and DNA metabarcoding of eDNA. Four species were detected with soil baiting (P. agathidicida, P. cinnamomi, P. multivora, and P. pseudo-cryptogea) and an additional three species with metabarcoding (P. kernoviae, P. cactorum/P. aleatoria and an unknown clade 7 species). Phytophthora cinnamomi was the most abundant species and was distributed throughout the forest. Both P. multivora and P. agathidicida were limited to forest edges, suggesting more recent arrivals. P. agathidicida presence was strongly correlated with declining canopy health, confirming its role as the main river of kauri dieback. The limited distribution of P. agathidicida and infrequent detections (11.0% samples) suggests that that this species is spreading as an introduced invasive pathogen and provide hope that with strategic management uninfected areas of the forest can be protected. The frequent detections of P.cinnamomi and P. multivora, from symptomatic trees in the absence of P. agathidicida suggest more research is needed to understand their roles in kauri forest health.

Authors evaluated the relevant literature related to the purging which is the interaction between selection and inbreeding where the population may get rid of its inbreeding load at least partially. The backroad of the relevant theory was given and the available methods were described both based on the conventional quantitative genetic approach (based on genealogy data) and based on the latest genomic methods. The different parameters necessary for signalling purging (highlighting those inbreeding coefficients which are not yet been widely known in animal and veterinary science) were presented together with the relevant results of the literature. The available statistical methods together with the softwares and R packages to calculate various inbreeding coefficients and to determine inbreeding depression and purging were provided. The main results of the different approaches obtained in laboratory ZOO and domesticated populations (lethal equivalents, ancestral inbreeding, Inbreeding-Purging Model, genomic approaches) were summarized and presented. Application possibilities and future prospective of purging was also discussed.

Coronavirus disease 2019 (COVID-19), an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors suffer from the lingering health effects of severe acute respiratory syndrome virus 2 (SARS-CoV-2), the pathogen that causes COVID-19. One of the diseases manifesting as a post-acute sequela of COVID-19 is new-onset diabetes. This systematic review and meta-analysis will perform a comprehensive and systematic literature search to estimate the burden of new-onset diabetes after COVID-19. Specifically, this study will estimate the magnitude of the incidence, risk, and population-attributable fraction of new-onset diabetes. The study will also explore and summarize the data on the natural history or clinical course of the new-onset diabetes cases. Five bibliographic databases, including PubMed, MEDLINE, Embase, Scopus, and Web of Science, will be searched for eligible studies. The World Health Organization COVID-19 Research Database, preprint servers, and conference abstracts will also be searched. Cohort studies of COVID-19 patients of all ages providing data on new cases of diabetes in the post-acute phase of the illness will be included. The comparators to estimate the pooled risk ratio will be those with no diagnosis of COVID-19 or those infected with other respiratory tract infections. The findings of this study will likely inform clinical practice, public health guidelines, and policies for early detection and treatment of new-onset diabetes cases in the long-COVID phase. This protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: No.CRD42020200432).

In the present work, we report on a 3D MOF of {[Pb5(3-OH)(3-NO3)3(6-pmdc)3·H2O}n formula (pmdc = pyrimidine-4,6-dicarboxylate) synthesized by an oven-heated solvent-free procedure. The large connectivity afforded by the three ligands in their coordination to lead(II) ions grows cubic building units characterized by a central Pb atom with an unusual coordination index of 12 and six pmdc ligands occupying the faces. These cubic units are linked one another giving rise to a quite condensed structure that represents an unprecedented topology showing the (4.62)6(43)2(45.610)3(45.68.82)6(46.69)6(612.83) point symbol. The crystalline material has been characterized by routine physico-chemical techniques to confirm its purity and its thermal behaviour has been also studied by thermogravimetric and thermodiffractometric analyses. The solid presents greenish blue photoluminescent emission based on pmdc ligands, as revealed time-dependent density-functional theory (TD-DFT) calculations, by that is substantially more intense than in free H2pmdc ligand according to its improved quantum yield. The emissive capacity of the material is further analysed according to decreasing temperature of the polycrystalline sample, finding that sizeable long-lasting phosphorescence is present.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western world. Mutations in different genes, such as TP53 and ATM, and deletions in specific chromosomal regions, including 11q or 17p, have been associated with a worse prognosis for the disease. Recent research from our group has demonstrated that, contrary to the usual cancer development process through missense mutations, B-CLL is driven by the overexpression of the small GTPase RRAS2 in its wild-type form, without activating mutations. While some mouse models of this disease have been developed to date and are commonly used in B-CLL research, they come with various disadvantages, such as a long waiting period until the leukemia fully develops, the need for cell engraftment, or, in some cases, a failure to replicate the alterations found in human patients. We have recently introduced Rosa26-RRAS2fl/flxmb1-Cre as a new mouse model of B-CLL with full disease penetrance. In this work, we have validated this mouse model as a novel tool for the development of new therapies for B-CLL by testing two of the most widely applied targeted agents: ibrutinib and venetoclax. This also paves the way for the development of new targeted agents against R-RAS2 itself, an approach that has not yet been explored in clinical practice.

Targeted cancer therapy has grown exponentially in the last decade, representing the largest frontier in the modern concept of precision medicine. This renaissance is largely due to our rapidly evolving ability to biochemically harness our immune systems to target cancer-specific antigens. Combined with an increasing armamentarium of surgical and non-invasive techniques for cancer mitigation we have upgraded cancer therapy from a non-specific assault on cell-division to a multi-modal, targeted approach. This renaissance has resulted in an increase in the perioperative footprint of patients with advanced cancer. The scope of the perioperative clinician has evolved from one of passive/reactive management of complications to a proactive approach that starts in the preoperative optimization phase and continues into the postoperative period. The perioperative world should not exist in a silo, and thus involvement of the oncology team is paramount. To provide safe oncologic care, it is essential to be up to date in newer cancer therapies, lest we act on erroneous and/or outdated information. Oncologists should weigh in on immune status, recent chemotherapeutic exposures, and potentially evolving toxicities. These might involve critical changes to perioperative infectious prophylaxis, steroid administration, and coagulopathy management. First, patients living beyond the typical life-expectancy for their cancer will carry a high burden of cancer-related downstream effects. General metabolic issues will include malnutrition, cachexia, and gastric outlet obstruction. Severe protein-calorie malnutrition, as well as hepatic and renal dysfunction can impact the metabolism and clearance of drugs. The cardiovascular, endocrinologic, pulmonary, and central nervous system implications of new cancer therapies will be discussed extensively below. Second, we have to enhance our ability to manage a cancer population who may be experiencing increasing novel chemotherapeutic toxicities. Newer agents differ from historical agents, which were blunt-force tools aimed at nonspecific destruction of cell-division. These drugs are efficacious but physiologically costly. Newer immunogenic therapies have a slightly improved acute safety profile, and a more complex chronic toxicity profile that may be overt or insidious. Chronic toxicities can present overtly or as a smoldering undertone to other active medical conditions such as sepsis, pneumonia, failure to thrive, or renal failure. The new therapies discussed in this review occur in the context of an overall increasingly multi-faceted cancer care machine. An example is screening for esophageal cancer in patients with Barrett's esophagus, or periodic chest CTs for patients with a strong history of tobacco use. These interventions are more likely to detect disease while it is still resectable, and resections will commonly accompany neo-adjuvant therapy. These approaches commonly involve new immunotherapies whose efficacy is higher-yield with a lower disease burden. In a recent example, the immune-checkpoint inhibitors (ICIs) ipilimumab plus nivolumab have significantly increased survival rate for squamous cell esophageal cancer when combined with standard chemotherapy. Surgical resection has evolved to one that often accompanies neoadjuvant chemo and radiation. The increasing efficacy of this approach may de-necessitate many major resections, and increase the number of sub-anatomic resections and minimally invasive procedures. Improved techniques - notably for hepatectomy, whipple procedure, prostatectomy, nephrectomy - have increased the safety profile and decreased the perioperative physiologic burden. This has enabled a broader subset of patients (due to cancer burden or due to medical comorbidities) to qualify for the operation, and increased the involvement of anesthesia and their perioperative services. With an increase in surgical candidacy comes an increase in post-surgical complications, and post-surgical maintenance such as drains, embolizations, imaging studies, etc. In the non-OR anesthesia realm, there have been considerable advancements in cancer “micro-treatments” such as hepatic metastasis embolization, tumor ablation, and peri-tumor vascular embolization. There are an ever-increasing number of IR-guided embolizations for bleeding tumors, aspiration of malignant effusions, and drainage of abscesses. This review serves to provide insight into new categories of chemotherapy and their perioperative implications.

The majority of Candida species are known as non-pathogenic yeasts and rarely involved in human diseases. However, recently case reports of human infections caused by non-albicans Candida species have increased, mostly in immunocompromised hosts. Our study aimed to describe and caracterise as thoroughly as possible, a new species of the Candida genus, named here Candida massiliensis (PMML0037), isolated from a clinical sample of human sputum. We compared genetic data based on the sequences of four genetic regions: "Internal Transcribed Spacers" of rRNA, D1/D2 domains (28S large subunit rRNA) and part of the genes encoding Translation Elongation Factor 1-α and β-tubulin2, to morphological characters, from scanning electron microscopy (TM 4000 Plus, SU5000), physiological, including the results of oxidation and assimilation tests of different carbon sources by the Biolog system, and chemical mapping by Energy-Dispersive X-ray Spectroscopy. Lastly, the in vitro antifungal susceptibility profile was performed using the E-testTM exponential gradient method. The multilocus analysis supported the genetic position of Candida massiliensis (PMML0037) as a new species of the genus Candida, and the phenotypic analysis highlighted its unique morphological and chemical profile when compared to other Candida species included in the study.

Design changes seem inevitable in engineering, procurement and construction EPC projects. Such changes create a need for a proactive approach to adjusting project scope, cost and time (the triple constraints) for efficiency and effectiveness in overall delivery. This study investigates the causes and implications of design changes in order to improve design change management practices. Data for the study was obtained through online interviews with New Zealand industry practitioners. Thematic analysis was used to collate the results into meaningful data. The study found that design changes were predominantly caused by clients' inadequate strategic planning, insufficient attention to design, EPC contractors' inadequate design ability, and on-site variations. There were three categories of such design changes: direct impact on the project, the reciprocal and complementary effect on stakeholders, and the far-reaching impact on the community. The study concludes by suggesting improvements, such as strengthening the integration of project teams to enhance design quality, strategic alignment of stakeholders at the planning stage, early contractor involvement (ECI) between the planning and design phases, and improving collaboration between design and construction teams. Further, a combination of high technical skills (e.g. design ability) and soft skills (can-do attitude, interpersonal skills, problem-solving skills, documentation skills, etc.) are needed to effect the desired improvement in design change management.

In order to establish a new discipline specializing in accident science from the perspective of safety science. Under the guidance of the current research theories and methods of safety science, combined with the research paradigm of humanities and social medicine, this paper puts forward new viewpoints, new theories and new models about accident research. First of all, through literature retrieval, this paper analyzes the relevant research results of accidents at home and abroad, and expounds the existing problems and the basic trend of accident science research. Secondly, it puts forward eight kinds of attribute relations of the accident, and makes clear the characteristics and connotation of the accident. In the study of accident types, a hierarchical classification model based on accident cognition is created for the first time. It also points out the logical relevance of five levels of accident science research and the realistic relevance of three levels. At the same time, according to the thought of science of science, this paper puts forward a new definition of safety under the thinking of accident science and other basic concepts related to safety science, and explains the connotation. In addition, it creates and constructs the basic concept of accident science, establishes the conceptual model of accident science, and points out the “3-4-5” model of accident science research and its connotation. Thirdly, draw lessons from the interdisciplinary paradigm to study the relevant theoretical basis and discipline classification relationship of accident science, and construct the tree of accident science. Finally, the research contents of three main aspects of accident science are summarized. The results show that the research results in this paper not only play a fundamental role in the basic construction of accident science, but also further enrich and perfect the discipline system of safety science, which has a certain theoretical significance.

This paper discovers that current variational principle and Noether theorem for different physics systems with (in)finite freedom systems have missed the double extremum processes of the general extremum functional that both is deduced by variational principle and is necessarily taken in deducing all the physics laws, but these have not been corrected for over a century since Noether's proposing her famous theorem, which result in the crisis deducing relevant mathematical laws and all physics laws. This paper discovers there is the hidden logic cycle that one assumes Euler-Lagrange equations, and then he finally deduces Euler-Lagrange equations via the equivalent relation in the whole processes in all relevant current references. This paper corrects the current key mistakes that when physics systems choose the variational extreme values, the appearing processes of the physics systems are real physics processes, otherwise, are virtual processes in all current articles, reviews and (text)books. The real physics should be after choosing the variational extreme values of physics systems, the general extremum functional of the physics systems needs to further choose the minimum absolute extremum zero of the general extremum functional, otherwise, the appearing processes of physics systems are still virtual processes. Using the double extremum processes of the general extremum functionals, the crisis and the hidden logic cycle in current variational principle and current Noether theorem are solved. Furthermore, the new mathematical and physical double extremum processes and their new mathematical pictures and physics for (in)finite freedom systems are discovered. This paper gives both general variational principle and general Noether theorem as well as their classical and quantum new physics, which would rewrite all relevant current different branches of science, as key tools of studying and processing them.

In this paper, we introduce two discrete degenerate random variables, namely the degenerate binomial and degenerate Poisson random variables. We deduce the expectations of the degenerate binomial random variables. We compute the generating function of the moments of the degenerate Poisson random variables, which leads us to define the new type degenerate Bell polynomials, and hence obtain explicit expressions for the moments of those random variables in terms of such polynomials. We also get the variances of the degenerate Poisson random variables. Finally, we illustrate two examples of the degenerate Poisson random variables.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.

The Median Based Unit Weibull is a new 2 parameter unit Weibull distribution defined on the unit interval (0,1). Estimation of the parameters using MLE encountered some problems like large variance. Using generalized method of moments (GMMs) and percentile method may ameliorate this condition. This paper introduces GMMs and the percentile methods for estimating the parameters of the new distribution with illustrative real data analysis.

We manufacture different Carbon Negative fuels at out manufacturing facilities. We manufacture fuel Butanol, fuel Isobutanol, fuel Diacetyl alcohol, and fuel Mesityl oxide. All said fuels are manufactured from the air CO2. Mixtures of our Carbon Negative fuels are great to fuel both Gasoline and Diesel fuel cars and trucks. The fuel mileage we can gather using said mixtures exceeds both either the Gasoline mileage aor the Diesel fuel mileage using respective cars / trucks. We publish herein the fuel mileage which always exceeds the gas and diesel fuel mileages for said fuels manufactured by the international petroleum corporations.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

Green innovation has become the mainstream of the era, and New Urbanization is an inevitable choice in the process of urbanization in China. Focusing on the topics of green innovation and new urbanization, much work has been done to find their factors respectively while the relationship between the two remains to be explored. Hence, in this article, representative indicators of new urbanization and green innovation are selected to study the Yangtze River Delta City Group from the perspective of both the entire urban agglomeration and a single city, in terms of time and space, using the entropy method and the coupling model. The results show that (1). Green innovation promotes the new urbanization development and there is a synergistic effect between the two systems. (2). The level of economic development is an important factor that affects the degree of coupling degree and coordination degree between the two interactions, and its influence is better than the spatial effect. (3). Green innovation and new urbanization have positive spatial autocorrelation and regional agglomeration (there are High-High, Low-Low, and High-Low collections).

Business school curriculums are designed to improve business skills and a student’s eventual workplace performance. In addition to these business skill sets the emerging business environment demands softer skills associated with ethical decision-making and sustainable business practices. Understanding the key influencers of ethical orientation and attitudes towards the environment is the first critical step for curriculum planning designed to develop both ethical decision-making and environmental sensibilities of students in business schools. Using a bivariate regression analysis (OLS) that compared the established New Ecological Paradigm (NEP) scale and the newly introduced Ethical Orientation Scale (EOS), this study assesses environmental eco-consciousness and ethical orientation over time and across varying socio-demographic variables. The study shows first, that in addition to socio-cultural variables, situational factors influence ethical decision-making. Secondly, it illuminates that ethical orientations as measured by the EOS predicts beliefs about the environment as measured by the NEP scale. It further provides evidence of the ethical underpinnings of the New Ecological Paradigm as well as provides initial validation for the new EOS. These outcomes provide additional levers to assist business educators in the creation of high impact teaching strategies to measure and encourage ethical decision-making and sustainable business practices that protect the environment.

Good transportation systems are pre-requisites to economic development. Materials used for road construction are traditionally classified based of empirically developed archaic tests, often classifying naturally available materials as unsuitable for use in the load-bearing road pavement layers. Consequently, design standards usually require the use of imported materials at considerable costs, severely restricting road network development under scenarios of limited funding. New technologies and test methods based on sound engineering criteria, incorporating basic material sciences can substantially change this scenario. Nano-silane technologies can be utilised to improve naturally available materials to meet the engineering requirements of all layers in road structures. Material test and design methods have been developed and successfully tested in South Africa to build New-age Modified Emulsion (NME) stabilised layers in roads, meeting all engineering requirements. Accelerated Pavement Tests (APT) done on actual roads, proved the concept. This work is based on a scientific approach and identification of various factors that will impact on the successful application of applicable nanotechnology solutions. This paper aims to identify these fundamental factors that are a pre-requisite for the evaluation of nanotechnology solutions to ensure that new technologies are introduced into pavement engineering designs at a low risk to any implementing.

The genus Aphanommata in the Old World is reviewed. Aphanommata kuscheli sp. nov. from São Nicolau and A. strakai sp. nov. from Fogo (both Cape Verde islands) are described. Aphanommata euphorbiarum (Wollaston, 1867) from Santo Antão in the Cape Verde islands is redescribed and its lectotype is designated. All three Aphanommata species from the Cape Verde islands as well as A. filum (Mulsant & Rey, 1859) from Old World are diagnosed, illustrated, and keyed. Mature larva of A. kuscheli sp. nov. is described, larval morphology is discussed and the current state of knowledge about immature stages of Cossoninae is summarized. Vertical and inter-insular distributional pattern of Cape Verde Aphanommata and Pselactus is reviewed and discussed.

Rapid urbanization has facilitated socioeconomic development but has also exacerbated land use/cover change (LUCC), significantly impacting ecological environments. Timely, objective, and quantitative assessments of ecological quality changes resulting from LUCC are essential for safeguarding the natural environment and managing land resources. However, limited research has explored the potential interrelationships between the spatio-temporal heterogeneity of LUCC and ecological quality during urbanization. This study focuses on Xiong’an New Area, a region experiencing rapid urbanization, utilizing the remote sensing-based ecological index (RSEI) to monitor ecological quality dynamics from 2017 to 2023. To address the computational challenges associated with large-scale regions, a streamlined RSEI construction method was developed using Landsat imagery and implemented via Google Earth Engine (GEE). A geographically weighted regression (GWR) analysis, integrated with Sentinel-2 land use data, was employed to examine the influence of LUCC on ecological quality. The findings reveal the following: (1) Ecological quality in Xiong’an New Area exhibited an overall positive trajectory, with improvements elevating the ecological status to above moderate levels. (2) Urban expansion resulted in a 17% reduction in farmland, primarily converted into construction land, which expanded by approximately 12%. (3) Ecological protection policies have facilitated the conversion of farmland into wetlands and urban green areas, which have emerged as the principal contributors to ecological quality enhancement. (4) A positive correlation was observed between changes in ecological land and ecological quality, while a negative correlation was identified between shifts in construction land and farmland and ecological quality. This research provides valuable scientific insights into ecological conservation and land use management, thereby establishing a foundation for the development of rational land resource planning and sustainable ecological development strategies in the Xiong’an New Area.

Parametric quantile regression is illustrated for the one parameter new unit Rayleigh distribution called Median Based Unit Rayleigh distribution (MBUR) distribution. The estimation process using re-parameterized maximum likelihood function is highlighted with real dataset example. The inference and goodness of fit is also explored.

In this article, we present solutions for one of the oldest mathematical problems, the Collatz Conjecture, and provide a proof for the Riemann Hypothesis, utilizing a new number theory based on newly discovered number properties, which will also be presented in this paper. This is made possible through the Sophy-Peter mathematical framework, built upon this new number theory. The Collatz Conjecture will be disproven, but as an alternative, the Oscillating Theorem will be introduced, with its correctness proven within this article. Furthermore, we present the general version of the Riemann zeta function, developed based on the new number theory. The correctness of this function is verified by comparing it with existing results of the zeta function. Using this approach and the Sophy-Peter framework, we have successfully proven the Riemann Hypothesis, long considered a millennium problem. Moreover, since the general zeta function is proven, this implies the correctness of the new number theory and the Sophy-Peter framework.

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

Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS, an electrode is surgically implanted into the medial forebrain bundle in the lateral hypothalamus or the ventral tegmental area in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the ICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of electrical ICSS is the lack of cellular selectivity in understanding the neural substrates underlying drug reward versus aversion. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models – dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable frequency-rate response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in these new behavioral models have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel experimental approach in preclinical medication development for treating substance use disorders.

Community-based case managers in health have been compared to glue which holds the dynamic needs of clients to a disjointed range of health and social services. However, case manager roles are difficult to understand due to poorly defined roles, confusing terminology, and low visibility in New Zealand. This review aims to map the landscape of case management work to advance workforce planning by clarifying the jobs, roles, and relationships of case managers in Aotearoa New Zealand (NZ). Our scoping and mapping review includes peer-reviewed articles, grey literature sources, and interview data from 15 case managers. Data was charted iteratively until convergent patterns emerged and distinctive roles identified. A rich and diverse body of literature describing and evaluating case management work in NZ (n=148) is uncovered with at least 38 different job titles recorded. 18 distinctive roles are further analysed with sufficient data to explore the research question. Social ecology maps highlight diverse interprofessional and intersectoral relationships. Significant innovation and adaptations are evident in this field, particularly in the last five years. Case managers also known as health navigators, play a pivotal but often undervalued role in NZ health care, through their interprofessional and intersectoral relationships. Their work is often unrecognised which impedes workforce development and the promotion of person-centred and integrated health care.

The main focus of this work is to extend the knowledge about the complexity of issues of oxidative stress. Natural compounds play a serious role in multiple aspects of both human, leading to clear health-promoting effects. This work is focused on the potential application cosmetic formulations containing including but not limited to of clove water and isolated clove oils on their aid in the control of the diseases. The aim of our work was to prepare to evaluate cosmetic formulations containing clove oil, eugenol or new eugenol ester derivative (eugenyl dichloroacetate - EDChA) but also cosmetic formulations containing the aqueous phase obtained after separation of essential oil following the clove buds steam distillation. To evaluate the antioxidants transdermal delivery system, in vitro permeation experiments in a Franz diffusion cell were performed using pig skin. The antioxidative capacity of the cosmetic formulations obtained was determined by the DPPH free radical reduction method. In the next stage, the antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin and of the fluid obtained after skin extraction, were also evaluated. For comparison, studies of cosmetic formulation containing alone dichloroacetic acid (DChAA) were as well carried out. The obtained cosmetic formulations were characterized by of antioxidant activity estimated after 24 hours of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The results of this work contribute to the development of cosmetic formulations with antioxidant potential, emphasizing that the water phases are waste from the process of cloves steam distillation and are not used to prepare cosmetic formulations. The use of waste water from the clove buds steam distillation process is environmentally friendly and not allows us to waste, containing however valuable biologically active compounds (furfural, methyl salicylate, 4-allilofenol, eugenol, α- and β-caryophyllene, eugenyl acetate, β-caryophyllene oxide). Together, these results suggest that cosmetic formulations may be potential drug candidates for chemopreventive, antineoplastic and antimutagenic therapy.

Exponential increase in mobile video delivery will continue with the demand for higher resolution, multi-view and large-scale multicast video services. Novel fifth generation (5G) 3GPP New Radio (NR) standard will bring a number of new opportunities for optimizing video delivery across both 5G core and radio access network. One of the promising approaches for video quality adaptation, throughput enhancement and erasure protection is the use of packet-level random linear network coding (RLNC). In this work, we discuss the integration of RLNC into the 5G NR standard, building upon the ideas and opportunities identified in 4G LTE. We explicitly identify and discuss in detail novel 5G NR features that provide support for RLNC-based video delivery in 5G, thus pointing out to the promising avenues for future research.

This article presents a description of a new method for solving the factorization problem, based on the gradient descent algorithm. This approach demonstrates significant improvements in efficiency compared to traditional methods proposed in previous research. This article describes a new method for solving the factorization problem, based on the gradient descent algorithm, and demonstrates the transition from algebraic methods to approaches based on functional analysis. The proposed approach not only improves the efficiency of solving the problem but also allows the application of computational algorithms of functional analysis, opening new possibilities for research and optimization.

This paper presents a new method for parameterizing the Lorentz group based on coupled parameters. From the Euler–Hamilton equations, an additional angular rapidity and perpendicular rapidity are obtained, and the Hamiltonian and Lagrangian of a relativistic particle are expanded into rapidity spectra. A so-called passage to the limit is introduced that makes it possible to decompose physical quantities into spectra in terms of elementary functions when explicit decomposition is difficult. New rapidity-dependent Lorentz-invariant coordinates are obtained, and the descriptions of particle motion using the old and new Lorentz-invariant forms as applied to plane waves are compared. Based on a classical model of particle motion in the field of a plane monochromatic electromagnetic wave and in that of a plane laser pulse, the rapidity-dependent spectral decompositions into elementary functions are presented, and the Euler–Hamilton equations are derived as rapidity functions in 3+1 dimensions.

We study the short−term memory capacity of ancient readers of the original New Testament written in Greek, of its translations to Latin and modern languages. To model the short–term capacity, we have considered the number of words per interpunctions, the “word interval” , because this parameter can model how the human mind memorizes “chunks” of information. Since can be calculated for any alphabetical text, we can perform experiments − otherwise impossible − with ancient readers by studying the literary works they used to read. The “experiments” compare the of texts of a language/translation to those of another language/translation by measuring the minimum average probability of finding joint readers (those who can read both texts because of their similar short–-term memory capacity) and by defining an “overlap index”. We also define a population of universal readers who can read any the New Testament written in alphabetical language. More than 50% of the readers of specific languages overlap with the universal readers with probability . Future work is vast, with many research tracks, because alphabetical literatures are very large and allow many experiments, such as comparing authors, translations or even texts written by artificial intelligence tools.

Using an original method for measuring weak radiothermal electromagnetic signals, experimental data were obtained on the analysis of dispersions of noise attractors of the radiobrightness temperature of aqueous solutions of NaCl, Al (NO₃)₃ at dilutions C1 (1:100) – C12 (12:100). The values of dispersions of noise attractors significantly differ from those for the control experiment with water. On the basis of the changed values of the noise attractors of the radiobrightness temperature, the values of the absorption coefficients of the solutions are calculated. The difference between the values of the solutions absorption coefficients and those for water is shown with a successive increase in their values with an increase in the degree of dilution. The difference between the values of the absorption coefficients of solutions of high dilutions and those for water is interpreted as a mechanism of cooperative interaction of ions with water molecules located outside the first hydration shell. A network of water molecules perturbed by ions contributes to the dielectric permittivity was obtained due to new properties at supramolecular interactions on the basis of dispersion interaction.

The transmission characteristic of COVID-19 is of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. The virus is now in more than 100 countries and on nearly all continents. The World Health Organization (WHO) declared the COVID-19 outbreak a pandemic. There is no current evidence from random clinical trials (RCTs) to recommend any specific anti-COVID-19 treatment for patients with suspected or confirmed COVID-19 infection. In order to mitigate the impact of the COVID-19 outbreak, here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated viruses might interact in co-infected patients. During SIT, the patient benefit from superinfection with an apathogenic dsRNA virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). Importantly, the epidemiological efficacy of a similar strategy to SIT had already been successfully tested in large controlled trials. Standard live orally administered enterovirus vaccines that stimulate the production of endogenous interferon of the host mitigated the seasonal outbreaks of influenza and other associated acute respiratory infections in 152,042 individuals without adverse reactions.

This paper is a mini literature review about electromagnetic field’s effects on cells, tissues and new treatment modalities. We have reviewed a papers which have been published in high quality journals in the last 5 years as two authors. This review’s aim is to be a resource for experimental studies about electricity’s effects on cell biology and pathophysiology. As a result of this literature review, we found that especially extremely low electric frequency and intermediate frequency fields have very important pathophysiological effects. We have mentioned four important expressions on this subject; electroporation, electrofusion, electrochemotherapy, gene electrotransference. Two different new treatment approaches have been developed by use of these two important electrical waves. First is tumor treating fields and the other is pulsed electric fields. Most studies in literature have been done with extremely low frequency and pulsed electric fields. In terms of diseases, most studies are about glioblastoma multiforme and malign melanoma.Most studies in literature have been done with extremely low frequency and pulsed electric fields. In terms of diseases, most studies are about glioblastoma and melanoma.

In this paper we describe many important aspects connected with lubricants, namely: the most cheapest organic lubricant in the word, how effectively save lubricant between pairs of friction, what kind of rational shapes for the lubricant must be, what it will be connected with wear and tear using the new organic lubricant (for this purpose formulas and curves are shown in computer program MathCad with calculation). Moreover, there is one physical model which helps to catch car exhausted gases. In conclusion, some recommendations will be given to realize them into the practice during the operation for the different mechanisms including ecology.

Mining industry is undergoing a revolution with the introduction of automation, especially through autonomous haul truck systems and is expected to have further essential developments due to advancements in swarm robotics and its applications. This study evaluates the performance of four different swarm robot models, i.e. baseline, ant, firefly, and honeybee, focusing on mining efficiency, scalability, reliability, and selectivity. Enhancements such as role specialization in the ant model, advanced communication in the firefly model, improved localization and the hybrid control system combining centralized and decentralized controls in the honeybee model are integrated to optimize their functionality. Mining simulations presented in this study include swarm robots of various designs, each resulting in certain advantages for autonomous operations. Their capabilities have been evaluated against performance criteria on a spider chart, identifying where each model excelled or failed in an actual extraction operation in mining. This study aims to identify the most optimal swarm models in relation to unique mining site conditions and goals. The applications of the suggested swarm models could contribute to achieving further improvement in productivity, scalability, selectivity and reliability, resulting in a more sustainable, automated and effective operations in mining.

In view of the complexity of the pile foundation underpinning structure system and the stringent requirements of the construction process, this paper briefly describes the necessity of introducing epoxy resin reinforcing adhesive of planting rebar in the design of pile foundation underpinning beam structure to im-prove the mechanical properties of the underpinning beam new and old concrete joint surfaces and proposes a new type of pile foundation underpinning beam system construction method by “chiseling + prestressed reinforcement + epoxy resin reinforcing adhesive”. This paper uses an actual pile foundation underpinning project of an urban overpass as a prototype, designs and creates a model structure with a similarity ratio of 1/6, and performs repeated pro-gressive static loading tests to study the load carrying capacity, displacement change, and other properties of the underpinning structure, as well as analyses and distorts the overall working performance and failure mode of them. On this basis, the prototype structure's finite element analysis model was built, and the finite element analysis results were compared with the test results to get the mechanical properties and deformation characters of the actual pile foundation under-pinning structure system corresponding to the actual underpinning beam load. This paper's study can lay the theoretical and experimental foundation for the smooth development of similar projects.

Constructing an innovation system centered on new-quality productivity is key to achieving China's technological independence and high-quality development, especially against the backdrop of rapid advancements in artificial intelligence. This article utilizes provincial panel data from China spanning 2010 to 2022 and applies kernel density estimation and the Moran's I index to study the spatiotemporal evolution of artificial intelligence and new-quality productivity. The findings indicate a clustering trend in the development of both factors across regions. Causal empirical analysis using a two-way fixed-effects model reveals that artificial intelligence positively influences new-quality productivity, with conclusions validated by robustness and endogeneity tests.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

The structure of existing activated models is inherently deficient in reflecting the major role of the membrane filtration. This study developed and proposed a novel model, MASM, for the membrane activated process. The effective filtration size imposed by the membrane module, entrapping larger size particles was adopted as the basis of the proposed model. The model defined a modified COD fractionation, accounting for the captured COD fractions as additional model components and utilizing related mass balance relationships. It was implemented for testing the fate of soluble hydrolysable COD and system performance of super-fast membrane activated sludge based on real data for the characterization and process kinetics of domestic sewage and denim processing effluents. Model evaluation was carried for parallel systems with gravity settling and membrane filtration operated at a sludge age range of 0.5-2.0 d. Results reflected significantly better performance of super-fast membrane activated sludge system for both wastewaters, underlining that it was crucially important to account for the captured COD fractions to provide an accurate evaluation of system behavior and effluent quality. This should also be identified as the major shortcoming of the ASM models for evaluating and predicting system performance of activated sludge configurations with membrane separation.

This paper discovers that current canonical variational principle and canonical Noether theorem of (in)finite freedom systems for different physics systems have neglected doublet extreme value processes of the general extreme value functional that both is derived by variational principle and is necessarily be taken in deriving all ( quantum ) physics laws in phase space, but which have not been done for over one century since Noether's showing her distinguished theorem, which lead to the crisis deriving all (quantum) physics laws (necessary) in phase space. We discover there is the hidden logic cycle that people assume canonical equations, and then they finally deduce canonical equations by the equivalent relation in the whole processes in all current references. We correct the current key mistake concepts that when physics systems take the variational extreme values, the appearing processes of the physics systems are real physics processes, otherwise, are virtual processes in all current references. The real physics should be what after taking the physics systems' variational extreme values, the physics systems' general extremum functional needs to further take the general extremum functional's minimum absolute extremum zero, otherwise, the appearing processes of physics systems still are virtual processes. Conservation current equations and conservation currents, in phase space, of general canonical variational principle and general canonical Noether theorem are, respectively, deduced for the first time. Using the general extremum functionals' doublet extreme value processes, the hidden logic cycle and the crisis in current canonical variational principle and current canonical Noether theorem are solved. Consequently, the new mathematical pictures, classical and quantum new physics in phase space and the new mathematical and physical doublet extremum processes for (in)finite freedom systems are discovered. General canonical variational principle and general canonical Noether theorem naturally are given, which would rewrite all the different sciences in phase space, as key tools of studying and dealing with them.

The American Civil War has been commemorated with a great variety of monuments, memorials, and markers. These monuments were erected for a variety of reasons, beginning with memorialization of the fallen and later to honor aging veterans, commemoration of significant anniversaries associated with the conflict, memorialization sites of conflict, and celebration of the actions of military leaders. Sources reveal that during both the Jim Crow and Civil Rights eras, many were erected as part of an organized propaganda campaign to terrorize African American communities and distort the past by promoting a ‘Lost Cause’ narrative. Through subsequent decades, to this day, complex and emotional narratives have surrounded interpretive legacies of the Civil War. Instruments of commemoration, through both physical and digital intervention approaches, can be provocative and instructive, as the country deals with a slavery legacy and the commemorated objects and spaces surrounding Confederate inheritances. Today, all of these potential factors and outcomes, with internationally relevance, are surrounded by swirls of social and political contention and controversy, including the remembering/forgetting dichotomies of cultural heritage. The modern dilemma turns on the question: In today’s new era of social justice, are these monuments primarily symbols of oppression, or can we see them, in select cases, alternatively as sites of conscience and reflection encompassing more inclusive conversations about commemoration? What we save or destroy and assign as the ultimate public value of these monuments rests with how we answer this question. In this essay, drawing from the testimony of scholars and artists, I address the conceptual landscape of approaches to the presentation and evolving participatory narratives of Confederate monuments that range from absolute expungement and removal to more restrained ideas such as in situ re-contextualization, removal to museums, and preservation-in-place.

In this paper, the new optical wave solutions of truncated M-fractional perturbed Kundu-Eckhaus model with full non-linearity are obtained by utilizing the expa function technique and modified extended tanh expansion function technique. The solutions are in the form of dark soliton, bright soliton, singular solitons and other form of solutions. The gained solutions are helpful for the further development of concerned model. The obtained results have also been presented graphically in both two-dimensional and three-dimensional formats to discuss the dynamical features as well as the parametric dependence of the constructed solutions. The study offers a highly spectacular and acceptable techniques to combine various intriguing wave demonstrations for more sophisticated models of the modern day.

This paper proposes a method of extracting energy from zero-point energy and evaluates the amount of energy gained. In addition, this electric circuit-based approach exhibits the Meissner effect, suggesting a new type of superconductivity that does not require refrigeration. The proposed method can provide extremely large amounts of energy, which is more than a conventional power station, without consuming fossil fuels or emitting radiation. Thus, it has the potential to solve the global energy problem. It involves preparing two electric loops containing diodes and connecting the loops together with current sources. The diodes are oriented in the same direction within each loop but in opposite directions in different loops. With this setup, the currents from the current sources build iteratively within the loops, resulting in large output currents. Our numerical analysis indicates that extremely large electric potentials are produced, which in turn yield large output currents. In addition, we confirm numerically that the voltage is zero around a loop and show analytically that the Meissner effect is present, proving the existence of a new type of superconductivity. Furthermore, when we introduce induction coils to not break the loop’s symmetry, they store extremely large amounts of energy and we can thus obtain energy from them via discharge currents.

The aim of this case-series report article is to provide a new topical view of the styletubation (video intubating stylet technique) in obese patients undergoing bariatric surgeries. In contrast to various conventional direct laryngoscopes (DLs), videolaryngoscopes (VLs) have been applied in such obese population with potentially difficult airway populations. The safety and effectiveness of VLs have been repeatedly studied and the superiority of VLs then has been observed and is advocated as a routine use. In this article, among our vast use experiences of the styletubation (more than 54,998 patients since 2016) for routine tracheal intubation, we present such unique experience to apply such intubating technique in obese patient undergoing bariatric surgery. Consistent with the experiences applied in other patient populations, we found the styletubation technique to be swift (the time to intubate from 5 s to 24 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satisfaction). The learning curve can be steep but is easily overcome if technical pitfalls are avoided. We, therefore, propose that the styletubation technique can be feasibly applied for tracheal intubation in obese patients undergoing bariatric surgery.

Product introductions play a pivotal role in the success and competitiveness of manufacturing, particularly in the context of new product development. Low-volume manufacturing companies exhibit distinct characteristics that significantly influence the product introduction process. Notably, the quality of information exchange between product design and production interfaces becomes paramount in this high-mix and low-volume industry. Consequently, there exists a pressing need to explore various methods for adapting and customizing management mechanisms and strategies to align with the unique requirements and characteristics of low-volume manufacturing and its associated product introduction processes. While the need for this knowledge is critical in the context of low-volume manufacturing, a majority of existing studies predominantly focus on the management aspects within high-volume manufacturing. Therefore, the primary aim of this study is to investigate the customization of product introduction management strategies to enhance the quality of information content within the realm of low-volume manufacturing. Drawing upon a longitudinal analysis of new product introductions within a low-volume manufacturing company, this study narratively elucidates how the examined company implemented product introduction management strategies to facilitate the enhancement of information content quality during the product introduction phase. The study presents its findings on management strategies across three key stages: pre-implementation, post-implementation, and subsequent modification and refinement of strategies following the initial round of implementation. By shedding light on these strategies, this study offers a comprehensive understanding of management approaches in the context of low-volume product introduction. As a result, it makes a valuable contribution to the discourse on information management and interface management in the high-mix, low-volume manufacturing literature.

We study two fundamental linguistic channels ‒ the Sentences and the Interpunctions channels ‒ and show they can reveal deeper connections between texts. The theory applied does not follow the actual paradigm of linguistic studies. As study‒case, we consider the Greek New Testament, with the purpose of determining mathematical connections between its texts and possible differences in writing style (mathematically defined) of writers, and in reading skill required to their readers. The analysis is based on deep‒language parameters and communication/information theory. To set the New Testament texts in the larger Greek Classical Literature, we consider texts written by Aesop, Polybius, Flavius Josephus and Plutarch. The results largely confirm what scholars have found about the New Testament texts giving, therefore, credibility to the theory. The gospel according to John is very similar to Fables written by Aesop. Surprisingly, the Epistle to the Hebrews and Apocalypse, are each other “photocopy” in the two linguistic channels, and not linked to all other texts. These two texts deserve further study by historians of the early Christian Church Literature at the level of meaning, readers and possible Old Testament texts which might have influenced them. The theory can guide scholars to study any literary corpus.

The efficiency of data sorting algorithms is the key aspect which determines the speed of data processing and searching. The best known efficiency of sorting algorithm has been Log (N) if there are N terms. All of the well-known sorting algorithms use various techniques to sort data. The basis for most of these are comparing the data terms with each other. In this manuscript, we are introducing a new approach for sorting data. This method is postulated to have the highest efficiency ever achieved by any of the sorting algorithms. We achieve this by sorting data without comparing the data terms. Or achieving results of data comparison without comparing the terms explicitly.

Proteins having a variety of functions play many essential roles in maintaining various life activities in organisms. Various methods, by which new protein functions can be artificially produced, have progressed rapidly upon development in recombinant DNA technology and effective screening techniques. However, the obtainable scope of the new functions has been restricted in a narrow range, because only functions of presently existing proteins can be used. On the other hand, it has been considered that it would be impossible to create an entirely new protein, which does not show any meaningful homology with any other amino acid sequences of previously existing proteins. The reason is because one amino acid sequence for a protein cannot be selected out from an extraordinary large amino acid sequence diversity as ~10130. As a matter of course, it is impossible to design an amino acid sequence of a protein in advance and a gene encoding the protein cannot be also formed through random process. Nevertheless, extant organisms have generated a variety of entirely new proteins in some way to make full use of them. This means that extant organisms have equipped a mechanism with which entirely new proteins can be produced under the present core life system composed of protein, tRNA (genetic code) and gene. In this article, first I introduce the mechanism, with which entirely new proteins are created in extant organisms, and further propose a novel strategy for application of the mechanism to protein engineering through creation of entirely new proteins, which could contribute to development of various industries.

By modifying the basic definition of cosmic red shift, considering ‘speed of light’ as an absolute cosmic expansion rate and adopting ‘Planck mass’ as the basic seed of the observed large scale universe, it is certainly possible to review and revise the basic picture of ‘standard cosmology’ and in near future, a perfect model of ‘white hole cosmology’ can be developed. In this context we have developed five assumptions. First three assumptions are based on ‘time reversed’ black holes and seem to be well connected with General theory of relativity as well as Quantum mechanics. 4^th and 5^th assumptions are helpful in understanding current galactic dark matter and flat rotation speeds. It may be noted that, considering our first three assumptions and considering the Planck Legacy 2018 data’s enhanced lensing amplitude in cosmic microwave background power spectra - conceptually, a closed universe having a positive curvature seems to be a best fit for the observed universe. With reference to our recent publication [26], for clarity on the subject, in this short communication, we make an attempt to review and explain our proposed assumptions at fundamental level. Our aim is to see that, professional and non-professional cosmologists must understand the basics of workable quantum cosmology.

Several problems of radiative transfer are yet unsolved because of the difficulties of the calculations involved in them, especially if the intervening shapes are geometrically complex. The main goal of our investigation in this domain is to convert the formulas that were previously derived, into a graphical interface based on the projected solid-angle principle. Such procedure is now feasible by virtue of several widely diffused programs for Algorithms Aided Design (AAD). Accuracy and reliability of the process is controlled by means of the analytical software DianaX developed at an earlier stage by the authors. With this new approach the often cumbersome procedure of lighting and thermal exchange calculations can be simplified and made available for the neophyte, with the undeniable advantage of reduced computer time.

The central promise of personalized medicine is individualized treatments that target molecular mechanisms underlying the physiological changes and symptoms arising from disease. We demonstrate a bioinformatics analysis pipeline as a proof-of-principle to test the feasibility and practicality of comparative transcriptomics to classify two of the most popular in vivo diet-induced models of coronary atherosclerosis, apolipoprotein E null mice and New Zealand White rabbits. Transcriptomics analyses indicate the two models extensively share dysregulated genes albeit with some unique pathways. For instance, while both models have alterations in the mitochondrion, the biochemical pathway analysis revealed, Complex IV in the electron transfer chain is higher in mice, whereas the rest of the electron transfer chain components are higher in the rabbits. Several fatty acids anabolic pathways are expressed higher in mice, whereas fatty acids and lipids degradation pathways are higher in rabbits. This reflects the differences between two translational models of atherosclerosis. This study validates transcriptome analysis as a potential method to precisely identify altered cellular and molecular pathways in atherosclerotic disease, which can be used to individualize treatment even in the absence of genetic data.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific biological pathways in a pathological manner, which we term pathophysiological pathways or patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of dysactivity (out of context activity that is at the wrong time and/or place), which is characteristic of age related disease. As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions to reduce ageing.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Nano-scale organofunctional silanes have been developed, tested and successfully applied to protect stone buildings in Europe against climatic effects since the 1860s. The same nanotechnologies can also be used in pavement engineering to create strong chemical bonds between a stabilising agent and the material substrata. The attachment of the organofunctional silane to a material also makes the surface of the material hydrophobic, reducing future chemical weathering. These properties allow naturally available materials to be used in any pavement layer at a low risk. In the built environment, scientists soon determined that the successful use of an organo-silane depends on the type and condition of the stone to be treated. The same principles apply to the implementation of applicable nanotechnologies in pavement engineering. Understanding the basic chemistry determining the properties of the stabilising agent and the organofunctional modifying agent and the chemical interaction with the primary and secondary minerals of the material are essential for the successful application of these technologies in pavement engineering. This paper explains some basic chemistry which fundamentally influences engineering outputs that can be achieved using New-age (Nano) Modified Emulsions (NME) stabilising agents with naturally available material in all road pavement TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

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

Amyotrophic lateral sclerosis (ALS) disease clusters are found in several countries worldwide. In the United States, ALS clusters are found in many states, largely within the northern United States. The cause of the increased rates of ALS in these areas remains indefinite. It is reported here that many ALS clusters are associated with sites of current or prior glacial lakes, or regions containing an abundance of silts and clay minerals. The potential significance of these findings in ALS is discussed.

Progesterone receptor (PGR) expression level determines biological characteristics of the serous ovarian carcinoma, and low PGR expression appears to be associated with chemoresistance and worse outcome. In this study, we aimed to find relationships between tumor progesterone receptor level and RNA-profile (miRNAs, piwiRNAs, and mRNAs), determining its biological characteristics and behavior. For this purpose, we applied next generation sequencing of small noncoding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze FFPE and frozen tumor samples as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumour (SBT), low-grade and high-grade serous ovarian carcinoma (LGSOC and HGSOC, respectively). We found significant upregulation of MMP7 and MUC16 and downregulation of PGR in LGSOC and HGSOC in comparison with BSC. The tissue content of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, miR-125b-5p significantly inversely correlated with the expression level of MUC16 and blood serum CA125 concentration, and significantly directly correlated with the PGR expression level in tumor tissue. On the contrary, the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, miR-93-5p, responsible for epithelial-mesenchymal transition (EMT) of the cell, significantly directly correlated with the blood serum CA125 concentration and significantly inversely correlated with the PGR expression level in the tumor tissue. Levels of the EMT-associated miRNAs significantly directly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, hsa_piR_019914 in tumor tissues. Among them, expression level of hsa_piR_004307 significantly inversly correlated with the PGR expression level in the tumor. Two optimal logistic regression models were developed based on the quantitation of hsa_piR_020813, miR-16-5p, hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, miR-93-5p in the tumor tissue, both of which significantly diagnose PGR-negative tumor phenotype with 93% sensitivity. According to FunRich3.1.3 functional enrichment analysis tool, 72 gene-targets of miRNA and piRNA identified here as markers of PGR-negative ovarian tumor phenotype were proven to be mutated in different cancers such as ovarian, breast, colorectal, liver, stomach, lung, endometrial, thyroid cancer. Among them, the blood plasma levels of miR-16-5p and hsa_piR_022437 can be used to diagnose PGR-negative tumor phenotype with 86% sensitivity before surgery and chemotherapy to choose the treatment strategy for this most aggressive type of ovarian cancer (for instance, neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy) to increase the effectiveness of treatment and longevity of the patient.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

This paper explores the challenges faced by blue-collared international migrants in adapting to new and unfamiliar climates while pursuing job opportunities, with a focus on poverty alleviation. Drawing on existing research and empirical evidence, the study investigates the trials encountered by these migrants as they navigate climate shocks and assesses the potential impacts on poverty reduction efforts. The findings underscore the significant difficulties blue-collared migrants experience when confronted with abrupt changes in climate conditions, adversely affecting their physical and mental well-being, as well as their employment prospects. The process of adjustment involves not only acclimating to new climate patterns but also navigating cultural nuances and social dynamics, exacerbating stress and feelings of isolation. Consequently, these challenges can perpetuate poverty by disrupting employment stability and limiting opportunities for career advancement. To address these issues, the paper proposes comprehensive support measures, including targeted pre-departure training programs, access to retraining opportunities, and assistance in securing sustainable livelihoods. By prioritizing climate resilience and empowering blue-collared migrants to adapt effectively to new climates, it becomes possible to enhance their livelihood prospects, reduce poverty levels, and foster sustainable development. The paper concludes by highlighting the significance of integrating climate adaptation strategies with poverty alleviation efforts to create a more inclusive and resilient future for blue-collared migrants in their pursuit of sustainable livelihoods.

Forest carbon sequestration is a widely accepted natural climate solution, however, methods to determine net carbon offsets are limited to commercial carbon proxies and CO2 eddy covariance research. Non-CO2 greenhouse gases (GHG) (e.g., CH4, N2O) receive less attention in the context of forests, in part, due to emphasis on CO2 and the operational requirements and cost for three-gas eddy covariance platforms. In this study, Howland forest flux tower (CO2, CH4) and soil flux data (CO2, CH4, N2O), representing net emission reductions, are linked to their respective social costs to estimate commercial revenue if sold as a GHG social cost forest offset product (GHG-SCF). Estimated annual revenue for GHG-SCF products, applicable to realization of a Green New Deal, range from 120,000 covering the site area of 557 acres in 2021, to 12,000,000 for extrapolation to 40,000 acres in 2040, assuming a 3% discount rate. The Howland Forest CO2 flux record for two adjacent towers is compared to California Air Resources Board forest carbon proxy data for compliance sequestration offsets, the only project site where these approaches overlap. Overcrediting, incomplete carbon accounting with annual errors of up to 2,256%, inadequate third-party verification, and limited application to non-CO2 GHG’s are established. In contrast, direct measurement of one or more GHG’s offers new forest products and revenue incentives to restore and conserve forests worldwide.

This article addresses the question why initiatives in the field of green business and sustainable development often fail. Therefore, it dismantles some typical patterns of failure and shows – as a case study – how these patterns can be challenged through an innovative educational concept: the green business and sustainable development school. The applied methodology is a real-life project that is designed through blended, interdisciplinary elements from business model canvas, Theory U, participation and design thinking. The results of the school initiative are discussed and evaluated by four distinctive stakeholder groups and outline the school’s supporting potential to overcome typical patterns of failure by the younger generation in the future. This article concludes with ideas to enhance the school concept reaching out to even more stakeholder-groups to increase its reliability and viability.

While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.

The use of New-age (Nano) Modified Emulsions (NME) for the stabilisation of marginal materials for use in the upper-pavement layers of roads have been proven in laboratories, through Accelerated Pavement Tests (APT) and in practice. In addition, material design methods have been developed based on the scientific analysis of granular material mineralogy and the chemical interaction with the binder to design a material compatible NME stabilising agent for naturally available (often marginal) materials. However, the introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology enables the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In practice, few road construction projects are without any problems. The introduction of new-technologies obviously makes it an easy target to blame for any non-related problem that may arise during construction. This article aims to assist in pre-empting, recognising, preventing and resolving material or non-material related construction problems through the correct identification of the cause of the problem and recommending the best, most cost-effective way to correct any deficiencies on site.

The use of naturally available materials not conforming to traditional specifications or standards, in the base and sub-base layers of road pavement structures, stabilised with New-age (Nano) Modified Emulsions (NME), have been tested, implemented and successfully verified through Accelerated Pavement Testing (APT) in South Africa. This was made possible through the development and use of a design procedure addressing fundamental principles and based on scientific concepts, which are universally applicable. The understanding of and incorporation of the chemical interaction between the mineralogy of the materials and a NME stabilising agent (compatibility between the chemistry of the reactive agents and material mineralogy) into the design approach is key to achieving the required engineering properties. Stabilised materials evaluation is done using tests indicative of the basic engineering properties (physics) of compressive strengths, tensile strengths and durability. This article describes the basic materials design approach developed to ensure that organofunctional nano-silane modified emulsions can successfully be used for pavement layer construction utilising naturally available materials, at a low risk. The enablement of the use of naturally available materials in all pavement layers can have a considerable impact on the unit cost and life-cycle costs of road transportation infrastructure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

: Nanotechnology options to road surface maintenance offers several advantages compared to traditionally used materials. The small particle sizer of hydrophobic Nano-Silane modified Nano-Polymers (NSNP) enables these nanotechnology products to deeply penetrate existing road surfaces, sealing micro-cracks and render surfacings to be water-resistant for extended periods of time. In comparison, traditionally used products contain minimum partial sizes of about 1 – 5 microns, that provide a superficial protection that wears off in a relatively short period of time. These traditional products are often associated with vehicle contamination while drying and requires the re-instatement of road markings. None of these disadvantages are associated with applicable NSNP technologies that are quick drying, with no vehicle contamination risks and is equivalent to a “clear-seal” requiring no reinstatement of road markings. In a similar vein, pot-hole repairs can be done using applicable, easy to use, pre-packed and treated pot-hole repair kits that are water-repellent and quick-drying at a fraction of the costs of conventional cold-mix products. Resurfacing using NME binder slurries can be done labour-intensively on a pre-treated NSNP surfacing, restoring cracked surfacing and providing a water-resistant long-lasting protective layer without the removal of existing cracked areas. The implementation of nanotechnology solutions for road surface maintenance operations is directly associated with ease of use, labour-intensive operations, prevention of considerable deterioration in riding quality due to removal and manual re-instatement of cracked surfaces, time and cost savings and a reduction in the risk of water damage to the sub-structure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

There are many molecules used as drug carrier. TUD-1 is a newly synthesized mesoporous silica (SM) molecule possess two important features; consists of mesoporous so it is very suitable to be drug carrier in addition to that it has the ability to induce apoptosis in cancer cells. However, the effect of TUD-1 appears to act as cell death inducer, regardless of whether it is necrosis or apoptosis. Unfortunately, recent studies indicate that a proportion of cells undergo necrosis rather than apoptosis, which limits the use of TUD-1 as a secure treatment. On the other hand, lithium considered as necrosis inhibitor element. Hence, current study based on the idea of production a new Li/TUD-1 by incorporated mesoporous silica (TUD-1 type) with lithium in order to produce a new compound that has the ability to activate apoptosis by mesoporous silica (TUD-1 type) and at the same time can inhibit the activity of necrosis by lithium. Herein, lithium was incorporated in TUD-1 mesoporous silica by using sol-gel technique in one step synthesis procedure. Moreover, lithium was incorporated in TUD-1 with different loading in order to form different active sites such as isolated lithium ions, nanoparticles of Li2O, and bulky crystals of Li2O. The ability of the new compounds to induce apoptosis and prevent necrosis was evaluated on three different types of cancer cell lines which are; liver HepG-2, Breast MCF-7 and colon HCT116. The obtained results show that Li/TUD-1has the ability to control necrosis and thus reduce the side effects of treatments containing silica in the case of lithium has been added to them, especially in chronic cases. This has been demonstrated by the significant increase in the IC50 value and cell viability comparing to control groups. Consequently, the idea is new, so it definitely needs more develop and test with materials that have more apoptotic impact than silica in order to induce apoptosis without induction of necrosis.