Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

This comprehensive critical review shows how green buildings and energy optimization solutions improve indoor air quality as well as environmental quality (IEQ) and human health. Electricity-efficient green buildings create a better indoor atmosphere and save electricity. Green buildings improve occupant well-being through IAQ, thermal comfort, acoustics, and lighting. Renewable energy, green construction materials, and intelligent technologies increase sustainability and reduce environmental impact. Environmental hazards, architectural design, and societal variables can improve indoor air quality and subsequently reduce health risks linked with poor air quality. The evaluation highlights the pros and cons of low-cost IAQ sensors and equipment. These devices provide valuable insights, but calibration and validation using reference equipment are necessary to ensure accuracy and reliability. Architects, engineers, environmentalists, and policymakers are essential in creating green buildings with high IEQ. Prioritizing occupant comfort, health, and productivity ensures a sustainable and healthy future for future generations. However, continual monitoring and research are needed to improve green building practices and overcome construction problems. Intelligent models for continual on-field calibration of low-cost sensors may improve performance. Green buildings benefit occupants and the environment by optimizing energy use and using IAQ monitoring technologies.

The field dynamics of neutral and charged matter (treated as gauge fields) beyond the event horizon of black holes are investigated. As an extension of the work done in Ganesan (2023) [1], the analysis was done using the combined dynamics of the two-dimensional Yang-Mills and Liouville gravity fields beyond the event horizon. The quantum interactions and symmetry breaking mechanisms of the combined two-dimensional fields are discussed. The second part of this paper explores the quantum dynamics occurring at the event horizon. By considering the structure of the event horizon as a Möbius strip (embedded in three-dimensional space), a formulation for the lower bound of the first energy eigenvalue of a quantum particle (electron) at the event horizon is obtained.

Bimetallic Ni/Cu core-shell and Cu-Ni heterostructural micro- and nanoparticles were prepared using two simple successive reduction procedures. Monometallic Ni and Cu particles were synthesized for comparison. The phase constitutions and morphological features of the particles were studied by means of X-ray diffraction, energy-dispersive X-ray spectroscopy and scanning electron microscopy methods. All the obtained mono- and bimetallic particles were applied as electrocatalysts in the electrohydrogenation of p-nitrophenol (p-NPh). An additional electrochemical reduction of copper cations during the hydrogen saturation of Cu-containing particles was established. Some of the prepared particles exhibited high catalytic activity with an increase in the hydrogenation rate of p-NPh by more than 3 times compared to its electrochemical reduction on the non-activated cathode, and p-NPh conversion yielded the maximum values. The main product of p-NPh electrocatalytic hydrogenation over Ni-Cu particles is p-aminophenol, which is an intermediate in the synthesis of many drugs. p-Aminophenol formation is confirmed by UV-Vis spectra.

Analyzing urban-rural spatial structures and changes are of great significance for under-standing the urban-rural relationship evolution. While previous studies mostly focused on the urban internal spatial structure evolution, less from the regional scale to explore the urban and rural evolution. Here, taking Dezhou city, a rapidly urbanization city in China as a case study, we employed the local contour tree method and nighttime light data to map urban and active rural regions’ range during 2012-2020, and further explored the respective development processes of them. This study found that different from rural regions, internal structures of urban regions are more complex, and there are often multiple hot spots inside them. The urban-rural regions’ area had increased significantly by 39.3% during 2012-2020 (p<0.05). The urban and rural region rankings of the identified counties are basically consistent with the urban and rural population rankings. Particularly, different from perspectives of earlier land use (i.e., built-up land or impervious surface), this study identified urban and active rural regions in view of the scope of active human activities. This study therefore found populations were greatly responsible for affecting changes of urban and active rural region structures. These findings could be helpful for understanding urban-rural dynamics.

Introduction SARS-CoV-2 infection normally damages respiratory system but may likewise impair endocrine organs’ function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. Onset of T1D and associated complications including DKA, hospitalization and death, are thought to be increased during the COVID-19 pandemic. The aim of this study is to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Methods: A systematic review was conducted using electronic databases PubMed and Google Scholar. The keywords “T1D, T1DM, Type 1 DM or Type 1 Diabetes”, “Coronavirus, SARS-CoV-2 or COVID-19” were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Result: we selected 21 manuscripts out of 296 identified studies. Data about the incidence rate of T1D, hospitalization and death are not consistent across countries, but DKA incidence and severity seem to be higher during the COVID-19 pandemic. Conclusion: Our data collection demonstrated that COVID-19 may or may not increase the incidence of type 1 diabetes. Nevertheless, it is associated with higher incidence and severity of DKA in T1D patients. Antivirals are not fully protective against endocrine complications of SARS-CoV-2 infection. Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.

Taking a certain type of test centrifuge as the research object, the finite element model of the test centrifuge is established, the vibration characteristics and aerodynamic performance of the test centrifuge are analyzed, and the structural optimization design of the test centrifuge is carried out. In this paper, the load is applied according to the actual working condition of a certain type of test centrifuge. The vibration of the mounting seat of the test centrifuge is analyzed and the structure of the mounting seat is optimized. After optimization, the vibration of the mounting seat is 77.38 % lower than that of the original mounting seat. Then, the aerodynamic analysis of the test centrifuge is carried out. The analysis results show that the test centrifuge moves more smoothly under the whole package shell and the steady flow shell, and the resistance decreases and the shaft load decreases. Finally, the steady flow shell of the test centrifuge is optimized. The analysis shows that the increase of the width of the steady flow shell can reduce the resistance coefficient, which is helpful to the stability of the test centrifuge during operation and reduces the unbalanced response of the system caused by air resistance.

The constant increase in current density in electrical wires leads to increasingly significant heat losses due to Joule effect. Therefore, reducing the electrical resistivity of copper wires becomes necessary. To achieve this goal, the development of a composite material incorporating a more conductive reinforcement, the graphene, is a promising way. The design of a copper/graphene composite using a powder metallurgy-based method is presented. This synthesis method allows for interface control through the growth of CuO(Cu) nanoparticles tightly bonded to the reinforcement. It also involves the dispersion of graphene through ultrasonic treatment and its alignment within the matrix using a uniaxial pressing densification method. The increase in the hardness (+12 HV) demonstrates the effective dispersion and separation of graphene layers. The impact on the electrical properties of dendritic copper (ρe = 2.30 µΩ.cm) remains limited, with a decrease in electrical resistance of approximately 1.4%. However, for copper with higher electrical resistivity, flake copper (at 2.71 µΩ.cm) and brass at (7.66 µΩ.cm), reductions of 2.7% and 10% have been achieved, respectively. With the improvement of graphene quality, there is more room to improve the electrical properties. This work paves the way for the development of composites with improved electrical resistivity.

Extraocular eye muscles (EOMs) are innervated by axons of three ocular motor nuclei, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the EOMs, pro-vide an overview of vestibular pathway inputs to ocular motor nuclei, and describe congenital disorders that alter the development of ocular motor neurons. Oculomotor neurons originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae which are contra-laterally innervated. Trochlear motor neurons originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons originate variously in the rhombomeres r4-6 and innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow yielding a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. The ocular motor neurons are innervating somites, which receive innervates vestibular nuclei that connects with the brainstem motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders.

Several studies show that air pollution has become a major problem and a source of great concern. Part of the observed poor air quality can be attributed to the levels of ultrafine particles (UFP), generally defined as the fraction of particles with diameter less than 100 nm which, by their size, are able to enter the blood circulation causing adverse health effects. As the main route of entry into the body is inhalation, several epidemiological studies associate the presence of UFP to total mortality, cardiovascular and respiratory problems. Since there are apparently no worldwide normative references for the control of these particles, this global study aimed to characterise the methods and techniques used worldwide regarding the monitoring and management of UFP. For this purpose, a survey was carried out based on a questionnaire applied at global scale. The questionnaire design was based on a preliminary literature review on the main search engines for scientific publications to establish the state of the art. As a result of the application of the questionnaire, a total of 51 responses were obtained from 20 different countries on five continents, which provided an insight into the global profile of professionals interested in the control/study of UFP, the measurement methodologies they follow and the guideline values they apply, if any. Among them are public health professionals, academics and health engineers from various institutions, such as education, hospitals, research centers and regulators in the health sector. Most responses said are no specific methodologies for the measurement of UFP, nor national standards for it. Through the results obtained in this study, it can be concluded that it is urgent to adopt regulations to standardize the assessments as well as to establish guide values for the protection of the human health.

As a novel post-harvesting strategy, edible films and coatings for fruits and vegetables offer preservation measures to meet the growing needs of hunger and agricultural management. Albeit edible films and coatings would differ in their processing and physio-mechanical characteristics, but functionality is distinctly the same as they are designed to improve shelf-life, barrier, and nutritional properties of the food. With emerging concerns on sustainability, biomacromolecules have been widely considered for preparing edible films and coatings, which are Generally Recognized as Safe (GRAS) substances. Biopolymers, including polysaccharides, proteins, and lipids are the main sources of preparing edible films and coatings. These biomacromolecules make stable colloidal dispersions that deliver processing convenience with various formulation, blending, casting, coating, and film-forming methods. However, biopolymers based edible films and coating require improvements for their extended performance due to several structural and barrier limitations. Therefore, preparing blends and composites, incorporating target molecules to introduce different functionalities, and designing complex multilayers are among the many recent research approaches developed to overcome those limitations. Thereby ensuring enhanced food preservation and extended shelf-life, essential requirements of food waste management without or with minimal influence on the texture, flavor, and nutritional value of food and vegetables.

Since Darwin’s “Power of movement in plants” the precise mechanism of oscillatory plant growth remains elusive. Hence the search continues for the hypothetical growth oscillator that regulates a huge range of growth phenomena ranging from circumnutation to pollen tube tip growth and stomatal movements. Oscillators are essentially simple devices with few components. A universal growth oscillator with only four major components became apparent recently with the discovery of a missing component, notably arabinogalactan glycoproteins (AGPs) that store dynamic Ca2+ at the cell surface. Demonstrably, auxin-activated proton pumps, AGPs, Ca2+ channels and auxin efflux “PIN” proteins, embedded in the plasma membrane, combine to generate cytosolic Ca2+ oscillations that ultimately regulate oscillatory growth: Hechtian adhesion of the plasma membrane to the cell wall and auxin-activated proton pumps trigger the release of dynamic Ca2+ stored in periplasmic AGP monolayers. These four major components represent a molecular PINball machine a strong visual metaphor that also recognizes auxin efflux “PIN” proteins as an essential component. Proton “pinballs” dissociate Ca2+ ions bound by paired glucuronic acid residues of AGP glycomodules, hence reassesses the role of proton pumps. It shifts the prevalent paradigm away from the recalcitrant “acid growth” theory that proposes direct action on cell wall properties, with an alternative explanation that connects proton pumps to Ca2+ signaling with dynamic Ca2+ storage by AGPs, auxin transport by auxin-efflux PIN proteins and Ca2+ channels. The extensive Ca2+ signalling literature of plants ignores arabinogalactan proteins (AGPs). Such scepticism leads us to reconsider the validity of the universal growth oscillator proposed here with some exceptions that involve marine plants and perhaps the most complex stress-test, stomatal regulation.

The purpose of this original study is to critically analyze the emergence and development of the national models of financial regulation; international standards and codes; regional and national financial regulation and supervision (the case of UK, USA, Sweden, EU and Finland). The research raises both academic and regulatory concerns. It aims at shaping changes (innovations) in the supervisory practices of national and international regulators in response to new developments in FinTech markets, digital products, financial instruments and risks. Secondly, it will stimulate more systematic work on regulatory databases, registration and reporting procedures in various economies in different financial markets. The author identifies five main systems of national financial regulatory markets: the multi-tiered, multi-agency US system; the Twin Peaks model (UK); the mega-regulatory model (Sweden). There is a thorough review of international standards and institutions that work for the stability of financial systems. The analysis of regional and national systems of financial regulation and supervision is based on the examples of the EU and Finnish institutions. National macro and microeconomic regulation and supervision have been examined with a focus on the US Federal Reserve and the US Treasury. National and international regulatory institutions have been evolving along several lines. First, minimum capital and credit risk requirements for banks (80s of the 20th century) are complemented in the 21st century by buffer reserves, liquidity and leverage standards. Second, regulation focuses on ensuring the sustainability of the national economy. The regulatory focus is on ensuring the sustainability of national and global financial systems. Third, there is an increase in the number of supervised institutions. Fourth, there is a division of functions between central banks (macroeconomic regulation) and one or two mega-regulators (microeconomic regulation and supervision). Fifth, there is a division of labour between the international financial institutions (BIS, IMF, WB) and national regulators. Sixth, the focus is on protecting consumers and investors, and countering money laundering and the financing of terrorism. Seventh, there is an understanding for a common approach by central banks to new financial technologies and cybersecurity.

The notion of luck clustering has gained traction in recent years due to its potential influence on performance and decision-making across a range of domains. This study concentrates on the application of luck clustering in sports, with an emphasis on its consequences for performance metrics and strategic decision-making. We employ time series analysis to investigate the presence of luck clustering in sports data, such as win-loss records, scoring, and player rankings, while considering the role of the Principle of Luck Conservation in the observed clustering patterns. Our findings provide evidence of luck clustering in sports, implying that periods of high luck tend to be followed by more high luck events, and vice versa for low luck events. These insights carry significant implications for coaches, players, and teams, who can utilize the understanding of luck clustering to develop more effective strategies, manage resources efficiently, and ultimately enhance their performance. By enriching our comprehension of luck's nature and its effects on sports outcomes, this study contributes valuable knowledge for practitioners and researchers in sports analytics and performance management.

An inter- and transdisciplinary concept has been developed, focusing on the scaling of industrial circular construction using innovative compacted mineral mixtures (CMM) derived from various soil types (sand, silt, clay) and recycled mineral waste. The concept aims to accelerate the systemic transformation of the construction industry towards carbon neutrality by promoting the large-scale adoption and automation of CMM-based construction materials, which incorporate natural mineral components and recycled aggregates or industrial by-products. In close collaboration with international and domestic stakeholders in the construction sector, the concept explores the integration of various CMM-based construction methods for producing wall elements in conventional building construction. Leveraging a digital urban mining platform, the concept aims to standardize the production process and enable mass-scale production. The ultimate goal is to fully harness the potential of automated CMM-based wall elements as a fast, competitive, emission-free, and recyclable alternative to traditional masonry and concrete construction techniques. To achieve this objective, the concept draws upon the latest advances in soil mechanics, rheology, and automation and incorporates open-source digital platform technologies to enhance data accessibility, processing, and knowledge acquisition. This will bolster confidence in CMM-based technologies and facilitate their widespread adoption. The extraordinary transfer potential of this approach necessitates both basic and applied research. As such, the proposed transformative, inter- and transdisciplinary concept will be conducted and synthesized using a comprehensive, holistic, and transfer-oriented methodology.

Cognitive functions are based on neuronal plasticity, which is provided by various mechanisms involving numerous bioactive molecules, the most important of which are endocannabinoids (eCBs). Over the past three decades, a lot of data have been accumulated on the involvement of eCBs in the mechanisms of memory and other cognitive functions. These functions are impaired in neurodegenerative diseases such as Alzheimer's disease (AD) and temporal lobe epilepsy (TLE). The main pathological feature of neurons in AD and TLE is increased excitability; therefore, an activation of the endocannabinoid system, which controls cellular excitation, may be a promising approach in their therapy. The available information about the effect of (endo)cannabinoids on cognitive functions is contradictory, which may depend on the drugs used, their dose, and the experimental conditions. There is an extensive literature indicating a protective effect of cannabinoids in the treatment of neurodegenerative diseases in humans and in animal models of cognitive deficits. This review, focusing on the recent researches, is devoted to the analysis of the effects of endocannabinoid system activation on cognitive functions in norm and in the brain with neurodegeneration that occurs in AD and TLE diseases. Possible reasons for inconsistencies in the available data are discussed.

The mutation databases have vital importance in detecting genetic mutation and their corresponding phenotypes. The emergence of next generation sequencing genetic technologies has accelerated this process, and the growth of genetic disease identification has created a need for quality control and documentation of mutation-related information. Ethnic-specific mutation databases offer valuable information for researchers, and the article evaluates the homogeneity and effectiveness of these databases. The aim to raise awareness of NEMDBs to healthcare professionals, the general public, and researchers studying genetic disorders. The article also recommendations to improve the effectiveness of these databases.

There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides’ fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest methods to analyze the lipids in biological samples. Finally, we discuss the drug development strategies focusing on the ceramide synthases and ceramides as future therapeutic approaches in cancer therapy.

Objective: To visualize and analyze the published literature on diabetes and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field. Methods: This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic. Results: A total of 139 literature on research related to diabetes and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first authorSchmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations; Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high impact journals with 4 articles and 29 citations; among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes and pyroptosis (67 articles), diabetes and pyroptosis (60 articles), and diabetes combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles. Conclusions: Based on a comprehensive analysis of published literature in the field of diabetes and pyroptosis from 2011-2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes and pyroptosis related research in the future.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements, Spencer-Smith elements (in N. gonorrhoeae), Neisserial intergenic mosaic elements, IS elements of IS5, IS30, IS110, IS1595 groups, Nf1-Nf3 prophages, NgoФ1-NgoФ9 prophages, Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.

The COVID-19 pandemic has highlighted the vitalness of telehealth in our medical world, where considering a restructuring of healthcare services has become paramount. In fact, telemedicine has recently earned a valuable place in many specialties; and its implications in cardiology and cardiovascular medicine were among the leading interests. In this letter, we gathered previous evidence supporting the merit of telemedicine in the fields of cardiology and cardiovascular medicine—medical branches in which patients require meticulous care and continuous monitoring—as well as protrusions of concerns about the uncertainty regarding the efficacy of telemedicine’s future implications and technologies. In sum, in the context of this still on-going pandemic, medical institutions must strive to improve telehealth technologies and implement solid future research directions in this growing field—to be able to persevere in meeting the needs of the patients. As long as no conclusive evidence exists regarding the fields where telemedicine is most worthwhile, healthcare systems will always keep the dread of wasting resources on developing ineffective programs. We conclude that telemedicine has been attributed a considerable attention in managing cardiac and cardiovascular conditions; nevertheless, further studies with solid designs are still needed to confirm its validity and utility in those specialties.

Mining is an important industry, accounting for 6.9% of global GDP. However, global development promotes accelerated demand, resulting in the accumulation of hazardous waste in land, sea, and air environments. It reached 7 billion tonnes of mine tailings generated yearly worldwide, and 19 billion solid tailings will be accumulated by 2025. Adding to this, the legacy of environmental damage from abandoned mines is worrying; in Canada there are around 10,000 abandoned mines, 50,000 in Australia, 6,000 in South Africa, and 9,500 coal mines in China, reaching 15,000 by 2050. In this scenario, restoration techniques from mining tailing have become increasingly discussed among scholars due to their potential to offer benefits towards reducing tailings levels, thereby reducing environmental pressure for the correct management and adding value to previously discarded waste. This review paper explores available literature on the main techniques of mining tailing recycling and reuse and discusses leading technologies, including the benefits and limitations, as well as emerging prospects. The findings of this review serve as a supporting reference for decision-makers concerning the related sustainability issues associated with mining, mineral processing, and solid waste management.

Event-based vision is an emerging field of computer vision that offers unique properties such as asynchronous visual output, high temporal resolutions, and dependence on brightness changes to generate data. These properties can enable robust high-temporal-resolution object detection and tracking when combined with frame-based vision. In this paper, we present a hybrid, high-temporal-resolution, object detection and tracking approach, that combines learned and classical methods using synchronized images and event data. Off-the-shelf frame-based object detectors are used for initial object detection and classification. Then, event masks, generated per each detection, are used to enable inter-frame tracking at varying temporal resolutions using the event data. Detections are associated across time using a simple low-cost association metric. Moreover, we collect and label a traffic dataset using the hybrid sensor DAVIS 240c. This dataset is utilized for quantitative evaluation using state-of-the-art detection and tracking metrics. We provide ground truth bounding boxes and object IDs for each vehicle annotation. Further, we generate high-temporal-resolution ground truth data to analyze the tracking performance at different temporal rates. Our approach shows promising results with minimal performance deterioration at higher temporal resolutions (48 – 384 Hz) when compared with the baseline frame-based performance at 24 Hz.

Thin films of BiFeO3 (BFO), VO2 and BFO/VO2 were grown on SrTiO3(100) and Al2O3(0001) monocrystalline substrates using the RF and DC sputtering techniques. The surface of the films was characterized by profilometry, AFM, and XPS. The heterostructures have roughnesses between 0.2 and 16 nm and a grain size between 20 nm and 67 nm. XPS measurements show a higher proportion of the V4+ and Bi3+ oxides. In the Fe region, a higher proportion of Fe3+ is shown in the films. The homogeneous ordering, low roughnesses, and the oxidation states on the obtained surface show a good coupling in these films. The I-V curves show ohmic behavior at room temperature and change with increasing temperature. The effect of coupling these materials in a thin film shows the appearance of hysteresis cycles I-V and R-T, typical of materials with high potential in applications such as resistive memories and solar cells.

All living organisms require some metal ions for their energy production as well as metabolic and biosynthetic processes. Within cells, metal ions are involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been a tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted also by the successful applications of neural networks and deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarize recent DL applications enhancing the functional interpretation of metalloprotein structures.

The global increase of road infrastructure and its impact on the environment requires serious attention to develop sustainable and environmentally friendly road materials. One group of those materials is produced by using bitumen emulsion. However, there are still scientific and technical obstacles standing against its regular application. The bitumen emulsion formulation process and compositional optimization are subjected to a high number of degrees of freedom. Consequently, obtaining the desired product is mostly based on a series of random and tedious trials because of the enormous number of tests to be carried out. The current review of the physicochemical formulation may indeed be extensively used in helping to reduce the number of unnecessary experimentations as well as discuss the vital aspects in the bitumen emulsion production process. Among these, emulsion stability, viscosity, droplet size (and distribution), bitumen emulsion chemistry, the function of the emulsion components, surfactant type, acids or alkalis, and additives are all discussed and used to define the emulsion's physical properties and reactivity. Besides, current developments in the mechanisms of breaking and setting processes are also summarized. It is discussed how emulsions are graded based on their reactivity, particle charge, and physical features. Two emulsification techniques are outlined namely the colloid mill method and the High Internal Phase Ratio (HIPR) method. Furthermore, some emulsion formulation tools/theories were identified and are explained. In that way, optimized formulations can be used to offer a practical guide for bitumen emulsion manufacturers when trying to formulate a well-defined bitumen emulsion for its use in pavement infrastructure rather than simply to meet standard specifications. This review paper aims to enable the ultimate potential of the bitumen emulsion in the field of cold recycling technology by further following up the research progress of bitumen emulsion manufacturing, therefore, this paper reviews and discusses the literature available up to now on this topic, in road engineering and emulsion chemistry.

Sustainability is pivotal in the urban transformation strategy in order to reach more resource-efficient, resilient and smarter cities. The goal of being a sustainable city should drive the decisions for city interventions. Nonetheless, impacts need to be quantified, lacking of standard and/or common methodologies that could be replicable across multiple cities. There exist many initiatives aiming at defining indicators and assessment procedures, but without convergence in the definition of terms and application methodologies, making complex its real implementation. Within mySMARTLife project (GA#731297), a KPI-driven evaluation framework is defined with the aim of covering the multiple pillars of a city (i.e. energy, mobility, citizens, economy) in a holistic way. This methodology also defines the concepts and terms to guide urban planners and/or experts at time of implementing the framework in a specific city. The evaluation framework has been deployed in the three cities of Nantes, Hamburg and Helsinki and some lessons learnt have been extracted, such as the necessity of providing a definition of measurement boundary to avoid interpretations. Thanks to a co-creation strategy, the main difficulties and issues from the cities have been taken into consideration for increasing the replicability.

Cells that experience high levels of oxidative stress respond with the induction of antioxidant proteins through the activation of the transcription factor Nrf2. Nrf2 is negatively regulated by Keap1 which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we study protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptible to protein misfolding and inclusion formation upon oxidative stress. We propose that the intrinsically disordered regions within Nrf2 and the high cysteine content of Keap1 contribute to their oxidation and the ensuing misfolding. Our work reveals previously unexplored aspects of Nrf2 and Keap1 regulation and dysregulation by oxidation-induced protein misfolding.

Cannabis is among the oldest human domesticates and has been subjected to intensive artificial (human-mediated) selection throughout history to create a wide array of varieties and biotypes for diverse uses, including fibre, food, biofuel, medicine and drugs. This paper briefly reviews the available literature on the taxonomy, evolutionary origin and domestication of this plant, as well as its worldwide dispersal, in both its wild and cultivated forms. Emphasis is placed on Europe and especially on the Iberian Peninsula. Today, it is accepted that Cannabis is a monospecific genus with two subspecies, C. sativa subsp. sativa and C. sativa subsp. indica, originating in Europe and Asia, respectively, by allopatric differentiation after geographic isolation fostered by Pleistocene glacial-interglacial cycles. Palynological and phylogeographic evidence situates the Cannabis ancestor on the NE Tibetan Plateau during the mid-Oligocene. The timing and place of domestication is still a matter of debate between contrasting views that defend single or multiple Neolithic domestication centres situated in different parts of the Eurasian supercontinent, notably central/southeastern China and the Caucasus region. Recent meta-analyses have suggested that wild Cannabis may have already been spread across Europe in the Pleistocene, and its domestication could have occurred during the European Copper/Bronze ages. According to the available reviews and meta-analyses, pre-anthropic dispersal of Cannabis into the Iberian Peninsula seems to have occurred only in postglacial times, and the earlier signs of cultivation date to the Early Medieval Ages. However, the palynological and archaeological evidence used to date is insufficient for a sound assessment, and the development of thorough Iberian databases to address further meta-analysis is essential for more robust conclusions. Some clues are provided for these achievements to be fulfilled.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

Impure and pure casts have collected reasonable attentions over all the world. In this paper, Aluminum (Al) and Copper (Cu) cast alloys are considered to be studied. Multiple impure and pure Al-Cu cast alloys are established under the condition of very high temperatures. Then, all of the established alloys are examined by applying mechanical tests. More specifically, tests of hardness are exploited. Moreover, different quenching conditions are employed and analyzed. These are the water, air and oil. Consistent results are separately obtained for the impure and pure materials.

Applications in high-performance computing (HPC) may not use all available computational resources, leaving some of them underutilized. By co-scheduling, i.e. running more than one application on the same computational node, it is possible to improve resource utilization and overall throughput. Some applications may have conflicting requirements on resources and co-scheduling may cause performance degradation, so it is important to take it into account in scheduling decisions. In this paper, we formalized co-scheduling problem and proposed multiple scheduling strategies to solve it: an optimal strategy, an online strategy and heuristic strategies. These strategies vary in terms of the optimality of the solution they produce and a priori information about the system they require. We showed theoretically that the online strategy provides schedules with a competitive ratio that has a constant upper limit. This allowed us to solve the co-scheduling problem using heuristic strategies that approximate this online strategy. Numerical simulations showed how heuristic strategies compare to the optimal strategy for different input systems. We proposed a method for measuring input parameters of the model in practice and evaluated this method on HPC benchmark applications. We showed high accuracy of measurement method, which allows to apply proposed scheduling strategies in scheduler implementation.

It is shown that the 5D geodetic equations and 5D Ricci identities give us a way to create a new viewpoint on some problems of Modern Physics, Astrophysics, and Cosmology. Specifically, the application of the 5D geodetic equations in (4+1) and (3+1+1) splintered forms obtained with the help of the monad and dyad methods made it possible to introduce a new, effective generalized concept of the rest mass of the elementary particle. The latter leads one to novel connections between the General Relativity and quantum field theories, as well as all of that, including the (4+1) splitting of the 5D Ricci identities, brings about a better understanding of the magnetic monopole problem and the vital difference in the origins of the Maxwell equations and gives rise to surprising connections between them. The obtained results also provide new insight into the mechanism of the 4D Universe’s expansion and its following acceleration.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.

The impact of organizational accreditation and professional certification and the evidence-based measurable impact of those for both academic programs and affiliates is one of specific interest to universities and individuals in the healthcare management field [1]. The authors’ analysis examined the impact of hiring graduates from higher education programs that held external accreditation from the Commission on Accreditation of Healthcare Management Education (CAHME). Graduates’ affiliation with the American College of Healthcare Executives (ACHE) professional healthcare leadership organization was also assessed as an independent variable. Study outcomes focused on these graduates’ respective healthcare organization’s performance measures (cost, quality, and access) to assess the researchers’ inquiry into the perceived value of a CAHME-accredited graduate degree in healthcare administration and a professional ACHE affiliation [2]. The results from this study found no effect of CAHME accreditation or ACHE affiliation on healthcare organization performance outcomes. The study findings support the need for future research surrounding healthcare administration professional graduate degree program characteristics and leader development affiliations, as perceived by various industry stakeholders.

During the past few decades, hybrid nanoparticles (HNPs) based on a magnetic material and gold have attracted interest for applications in catalysis, diagnostics and nanomedicine. In this paper, magnetic CoFe2O4/Au HNPs with an average particle size of 10–20 nm decorated with 2-nm gold clusters were prepared using methionine as a reducer and an anchor between CoFe2O4 and gold. The obtained nanoparticles were studied by X-Ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy and X-Ray photoelectron spectroscopy (XPS) and UV-Vis spectroscopy techniques. The TEM images of the HNPs obtained after one, six and ten gold deposition cycles showed that the surface of cobalt ferrite was covered with gold nanoclusters, which slightly increased with an increase in the number of gold deposition cycles (from 2.12 ± 0.15 nm after one cycle to 2.46 ± 0.13 nm after ten cycles) without any change in surface density. The magnetic measurements showed that the obtained HNPs possessed typical ferrimagnetic behaviour, which corresponds to that of CoFe2O4 nanoparticles. The toxicity evaluation of the synthesised HNPs on Chlorella vulgaris indicated that they can be applied to biomedical applications such as magnetic hyperthermia, photothermal therapy, drug delivery, bioimaging and biosensing.

Gender Identity Dysphoria (GID) is a condition characterized by a strong and persistent identification with the opposite sex. These people consider themselves victims of a sort of biological accident: "a soul in a wrong body". There are numerous theories on the origin of transsexualism: genetic, hormonal and psychological causes have been hypothesized, but those currently most accredited are the neuroanatomical ones. The cornerstones of hormone conversion therapy (Gender Affirming Hormone Therapy, GAHT) are feminizing hormones for transgender women (MtFs) and virilizing for transgender males (FtMs). GID can be present among adolescents and older people. For adolescents is now accepted reversible treatment of puberty withdrawal with hormones that stops the progression of pubertal development in the biological direction not accepted; for elderly people is suggested GAHT in reduced doses. Physicians should consider and discuss with people with GID about fertility preservation, general and cancer risks. We present also data of 127 transsexual patients enrolled at the Garibaldi-Nesima Andrology Clinic in Catania (Italy) from 2003 to 2020. To optimize the conversion treatment with sex hormones, transsexuals require long-term follow-up. GAHT must be performed by a doctor who is familiar with these problems. Therefore, the “do-it-yourself” trend and the lack of medical and laboratory checks over time should be absolutely discouraged. Before proceeding with the surgical sex reassignment, it is recommended to refer to an endocrinologist and psychologist or psychiatrist for a period of 2-3 years. The transition surgical conclusion process must be practiced by a quality surgical team.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Issues presented by the application of monoclonal antibodies in diagnostic assays and as curative agents can make the use of such molecules cost-prohibitive and sometimes even unsafe. This has warranted the development of short single-stranded oligonucleotides known as Aptamers. The structural malleability of these short DNA or RNA nucleotide segments allows them to exist in distinct conformations. SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a multi-step process for synthesis of aptamers. Each step of this procedure is governed by a diverse set of factors that influence production efficiency, binding affinity, and specificity of the oligonucleotides. Headway in aptamer research has been made in recent years by the introduction of newer iterations of the SELEX process. A greater number of studies are now being carried out to incorporate aptamers into existing disease detection tools and therapies. An overview has been given first on the key aptamer properties and the process of their production (with its newer iterations), contrasting each of them with that of monoclonal antibodies. Possible manifold applications afforded due to unique aptamer characteristics are also discussed. A keen review is further provided on the design, development and use of fluorescent aptamers in bioimaging, sequencing or profiling, and treatment of pathogenic bacteria and tumor cells.

Information and Communication Technology (ICT) is at the heart of the Smart City approach, which constitutes the next level of cities’ and communities’ development across the globe. Thereby, ICT serves as the gluing component enabling different domains to interact with each other and facilitating the management and processing of vast amounts of data and information towards intelligently steering the cities infrastructure and processes, engaging the citizens and facilitating new services and applications on various aspects of urban life - e.g. supply chains, mobility, transportation, energy, citizens’ participation, public safety, interactions between citizens and the public administration, water management, parking and many other use cases and domains. Hence, given the fundamental role of ICT in cities in the near future, it is of paramount importance to lay the ground for a sustainable and reliable ICT infrastructure, which can enable a city/community to respond in a resilient way to upcoming challenges whilst increasing the quality of life for its citizens. This paper constitutes a continuation of a series of research documents and standardization activities, which relate to the concept of Open Urban Platforms (OUP) and the way they serve as a blueprint for each city/community towards the establishment of an ICT backbone. Thereby, the current paper emphasizes on the aspects of sustainability and resilient ICT, whilst reporting on our latest activities and related developments in the research area.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Carbohydrate and menthol mouth-swilling have been used to enhance exercise performance in the heat. However, these strategies differ in mechanism and subjective experience. Participants (n=12) sat for 60 min in hot conditions (35°C; 15±2%), following a 15 min control period, participants undertook three 15 min testing blocks. A randomised swill (Carbohydrate; Menthol; Water) was administered per testing block (one swill every three minutes within each block). Heart rate, tympanic temperature, thermal comfort, thermal sensation and thirst were recorded every three minutes. Data were analysed by ANOVA, with carbohydrate intake controlled for via ANCOVA. Small elevations in heart rate were observed after carbohydrate (ES: 0.22 ± 90% CI: -0.09 to 0.52) and water swilling (0.26; -0.04 to 0.54). Menthol showed small improvements in thermal comfort relative to carbohydrate (-0.33; -0.63 to 0.03) and water (-0.40; -0.70 to -0.10), and induced moderate reductions in thermal sensation (-0.71; -1.01 to -0.40 and -0.66; -0.97 to -0.35, respectively). Menthol reduced thirst by a small to moderate extent. These effects persisted when controlling for dietary carbohydrate intake. Carbohydrate and water may elevate heart rate, whereas menthol elicits small improvements in thermal comfort, moderately improves thermal sensation and may mitigate thirst; these effects persist when dietary carbohydrate intake is controlled for.

Upon inbreeding, the architecture of the inbreeding load shifts as selection purges strongly deleterious recessive mutations and drift fixes many milder ones. Most small inbred populations show limited genetic variation while crosses between such populations commonly express pronounced heterosis, confirming fixation. In contrast, purging appears to be limited in that inbred populations often retain substantial inbreeding depression. In addition we have the enigma Darwin noted: purely selfing taxa are unknown. Because both purging and fixation reduce inbreeding depression and load, another mechanism must exist to sustain these. Background selection and the associations that develop among alleles in small inbred populations will shift the architecture of the load potentially creating blocks of recessive mutations linked in repulsion. This would generate pseudo-overdominance that could sustain these “PODs” and inbreeding load. Recombination and crosses between lineages could erode PODs. Crosses between populations fixed for different mutations would generate high pseudo-overdominance, enhancing heterosis and potentially POD formation. New recessive mutations arising within PODs would reinforce overdominance. PODs should generate clear genetic signatures including genomic hotspots of heterozygosity and linkage disequilibrium containing alleles at intermediate frequency generating segregating load. Results from several simulation and empirical studies match these predictions. Further simulations and comparative genomic analyses are needed to rigorously test whether PODs exist in sufficient strength and number to generate persistent inbreeding depression and load in inbred lineages.

Cellular communications play pivotal roles in multi-cellular species, but they do so also in uni-cellular species. Moreover, cells communicate with each other not only within the same individual but also with cells in other individuals belonging to the same or other species. These communications occur between two unicellular species, two multicellular species, or between unicellular and multicellular species. The molecular mechanisms involved exhibit diversity and specificity, but they share common basic features which allow common pathways of communication between different, and sometimes very different species. These interactions have been made possible by the high degree of conservation of the basic molecular mechanisms of interaction of many ligand-receptor pairs in evolutionary remote species. These inter-species cellular communications played crucial roles during Evolution and must have been positively selected, particularly when collectively beneficial in hostile environments. We think that communications between cells did not arise after their emergence but was part of the very nature of first cells. Synchronization of populations of non-living protocells through chemical communications may have been a mandatory step towards their emergence as populations of living cells and explain the large commonality of cell communication mechanisms among microorganisms, plants, and animals.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Innovative interventions in the planning and design of stair and escalator facilities call for understanding their effects on stair use. This study considers five planning variables for the twinned stair and escalator facilities–stair pitch and width, angle of deviation, height and separating distance. Public sites were identified in 8 commercial districts in Beijing. Facilities (n=21) presenting heterogeneously across variables were sampled for simultaneous up and down pedestrian counts in 18 5-minute video segments middays, for a total of 1464 counts. Stair width accounts for 20% of the variance in ascending rate and 10% in descending. Plan angle accounts for 2% in ascending and 5% in descending, while pitch accounts for 1% in ascending and 5% in descending. The study confirms the effects of layout and design of stairway and escalator facilities on facility choice. The results point directly to interventions in support of higher stair-climbing rates.

We are proposing, for any interested investigator, a randomized open clinical trial for mild and mild-to-moderate Covid-19 comparing a treatment regimen with standard of care, and eventually with another investigational regimen, if ongoing or will be implemented. The patients could be hospitalized or ambulatory but not requiring admission to intensive care units and mechanical ventilation. The proposed therapeutic regimen consists of doxycycline (an antimicrobial having also anti-inflammatory properties, probable antioxidant and possible some antiviral effects), and pentoxifylline, a hemorheological compound used in occlusive arterial diseases but also having proven anti-inflammatory properties. Doxycycline is included in the WHO’s list of essential medicine being an effective, safe, widely available, and inexpensive medication and widely accessible. It will be administered at a dosage of 100 mg orally twice daily for ten days. Pentoxifylline, in clinical use since 1972, and also widely accessible, will be given at a dosage of 400 mg orally, also twice daily, for ten days. The primary outcome measures are: 1) Progression of disease to a severe form requiring intensive care admission and mechanical ventilation; 2) Fatality rates and 3) Time to clinical recovery.This proposal was presented to the National Directors and Core Leads meeting of the Canadian Trials Network (CTN) on May 6, 2020. The interventional trial template suggested by CTN was used for designing the trial.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

The world is puzzling over the origin of the current outbreak of the coronavirus disease (COVID-19) that is caused by a novel coronavirus-2019 (2019-nCoV). As of 26^th March 2020, the World Health Organization has reported 46,2,684 confirmed cases and 20,834 confirmed deaths in total due to COVID-19. To this end, two unique mammals namely bats and pangolins are being investigated for their potential link to COVID-19. However, the evidence so far gathered in this context is far from clear. This paper aimed to: (i) enlighten the major aspects of life of bats and pangolins; (ii) briefly discusses their potential link to COVID-19; and also (iii) to highlight the way forward. The outcomes may contribute to future research on the subject.

The ability to replicate scientific experiments is a cornerstone of the scientific method. Sharing ideas, workflows, data, and protocols facilitates testing the generalizability of results, increases the speed that science progresses, and enhances quality control of published work. Fields of science such as medicine, the social sciences, and the physical sciences have embraced practices designed to increase replicability. Granting agencies, for example, may require data management plans and journals may require data and code availability statements along with the deposition of data and code in publicly available repositories. While many tools commonly used in replicable workflows such as distributed version control systems (e.g. “git”) or scripted programming languages for data cleaning and analysis may have a steep learning curve, their adoption can increase individual efficiency and facilitate collaborations both within entomology and across disciplines. The open science movement is developing within the discipline of entomology, but practitioners of these concepts or those desiring to work more collaboratively across disciplines may be unsure where or how to embrace these initiatives. This article is meant to introduce some of the tools entomologists can incorporate into their workflows to increase the replicability and openness of their work. We describe these tools and others, recommend additional resources for learning more about these tools, and discuss the benefits to both individuals and the scientific community and potential drawbacks associated with implementing a replicable workflow.

As a part of our ongoing effort in the search for promising antileishmanial agents based on the thiochroman scaffold, we prepared a series of substituted 2H-thiochromenes. Thirty-three compounds were evaluated against intracellular amastigotes forms of L. (V) panamensis. Twelve compounds were active with EC₅₀ values lower than 40 μM, and among those three compounds displayed the highest antileishmanial activity with EC₅₀ values below 10 uM. Cytotoxicity was determined against human U-937 macrophages; thus, compounds having electrophilic alkenes (α,β-unsaturated carbonyl, or nitriles) displayed the highest antileishmanial activity but also moderate to high cytotoxicities. Based on SAR analysis, compounds 8d and 10, which differ only in the hydroxy group at C4, were selected as the most promising compounds in this library because good antiparasitic activity and Selectivity Index.

Two desirable functions of healthy soil are nutrient cycling and pest suppression. We review recent literature on the contributions of soil microarthropods to soil health through their intersecting roles in decomposition and nutrient cycling and direct and indirect suppression of plant pests. Microarthropods can impact soil and plant health directly by feeding on pest organisms or serving as alternate prey for larger predatory arthropods, and indirectly, by mediating the ability of crop plants to resist or tolerate insect pests and diseases through interactions with the decomposition food web in support of plant nutrition. Soil fauna, including microarthropods, are key regulators of decomposition at local scales but their role at larger scales is unresolved. Future research priorities include the incorporation of multi-channel omnivory into food web modeling and understanding the vulnerability of our soil carbon to increased global temperatures.

The procedures for the extraction and separation of lipids and nutraceutics from microalgae using classic solvents have been used many times. However, these production methods usually require expensive and toxic solvents. Based on our studies involving the use of eco-sustainable methodologies and alternative solvents, we select ethanol (EtOH) and cyclopentyl methyl ether (CPME) for extracting bio-oil and lipids from algae. Different percentage of EtOH in CPME favors the production of an oil rich of SFA useful to production biofuel or rich of compounds bioactive. The proposed method for obtain a rich extract of saturated or unsaturated fatty acids from dry algal biomass is disclosed is eco-friendly and allows a good extraction yield. The method is compared both in extracted oil percentage yield and in extracted fatty acids selectivity to extraction by supercritical carbon dioxide.

Residential dust is recognized as a major source of environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs). To characterize the thoracic dust fraction (PM10), a sampling campaign was carried out with an in-situ resuspension chamber in three rooms (kitchen, living room and bedroom) of four Spanish houses. Two samples per room were collected with, at least, a one-week interval. The PM₁₀ samples were analyzed for their carbonaceous content by a thermo-optical technique and, after solvent extraction, for 20 PAHs, 8 phthalate plasticizers (PAEs) and one non-phthalate plasticizer (DEHA) by gas chromatography-mass spectrometry. In general, higher dust loads were observed for parquet flooring compared with tile. The highest dust loads were obtained for rugs. Total carbon accounted for 9.3 to 51%wt of the PM₁₀ mass. Plasticizer mass fractions varied from 5 µg g-1 to 17 mg g^-1 PM₁₀, whereas lower contributions were registered for PAHs (0.98–116 µg g^-1). The plasticizer and PAH daily intakes for children and adults via dust ingestion were estimated to be 3–4 orders of magnitude higher than those via inhalation and dermal contact. Potential carcinogenic and negligible non-carcinogenic risks arising from exposure to PAHs were found.

We present a high-throughput nanoindentation study of in-situ bending effects on incipient plastic deformation behavior of polycrystalline and single-crystalline pure aluminum and pure copper at ultra-nano depths (<200nm). We find that hardness displays a statistically inverse dependence on in-plane stress for indentation depths smaller than 10nm, and the dependence disappears for larger indentation depths. In addition, plastic noise in the nanoindentation force and displacement displays statistically robust noise features, independently of applied stresses. Our experimental results suggest the existence of a regime in FCC crystals where ultra-nano hardness is sensitive to residual applied stresses, but plasticity pop-in noise is insensitive to it.

Glyphosate-based herbicide products are the most widely used broad-spectrum herbicides in the world for post-emergent weed control. There are ever-increasing concerns that glyphosate, if not used judiciously, may cause adverse non-target impacts in agroecosystems. The purpose of this brief review is to present and discuss the state of knowledge with respect to its persistence in the environment, possible effects on crop health, and impacts on crop nutrition.

Previous evidence in support of a slowly acting (scale of 100s of seconds) and volume-transmitted component of cholinergic signaling was based largely on studies using measures of extracellular brain acetylcholine (ACh) levels which required several minutes to generate a single data point and typically employed AChEsterase inhibitors (AChEIs) to foster the measurement of ACh. Moreover, collecting such data points in correlation with relatively stable behavioral states has supported the view that extracellular ACh levels vary at a relatively slow rate. Here we argue that forebrain cholinergic signaling is exclusively phasic (milliseconds to perhaps seconds), unlikely to be volume-transmitted, and that previous neurochemical evidence and associated behavioral correlates may be re-interpreted in terms of integrated phasic cholinergic activity and specific behavioral and cognitive operations. The highly potent catalytic enzyme for ACh, AChE, limits the presence of an ambient extracellular ACh level and thus renders it unlikely that ACh influences target regions via relatively slow changes in extracellular ACh concentrations. Real-time amperometric recordings of cholinergic signaling have suggested a specific function of rapid, phasic or transient cholinergic signaling in attentional contexts. Optogenetic studies support a causal relationship between these transients on behavior. Combined electrochemical and neurophysiological recordings revealed that the powerful behavioral control by cholinergic transients involves the generation of high-frequency oscillations. Such oscillations are thought to recruit efferent circuitry to (re)activate dormant task sets. Evidence showing the impact of genetic variations of the capacity of cholinergic synapses likewise can be interpreted in terms of their impact on the ability to sustain generation of repeated phasic cholinergic signals, as opposed to effects on ambient ACh levels. Further, while notions of slowly-changing, sleep stage-associated variations in extracellular ACh levels and their functions are widely accepted, the evidence is in fact limited. An alternative hypothesis offers a role for high-frequency cholinergic transient signaling during REM sleep. By employing a theoretical framework that focuses on the phasic and causative characteristics and functions of cholinergic signaling, results from human cognitive neuroscience studies of cholinergic function may be substantially clarified and simplified. Compared to the current treatment of cholinergic deficits using AChEIs, the conceptualization of forebrain cholinergic signaling as wired, phasic, and causative predicts that drugs that either rescue transient presynaptic signaling or amplify or rescue the postsynaptic impact of phasic signals will be more efficacious in treating age- and dementia-related cognitive and cognitive-motor disorders.

The paper presents Jonathan Swift's Gulliver's Travels as the first attempt to claim that thought experiments, namely the close analysis of contrived counterfactual scenarios, are the only way we challenge normative framework assumptions and learn anything significantly new in and outside science. The standard epistemologies of his day – Baconian empiricism and Cartesian rationalism –fiercely ridiculed in the course of Gulliver's third voyage, are cruelly dismissed as powerless to advance knowledge, and keep it in normative check. The transformative effect of the clever thought experiments presented in the three other voyages (of imagining London shrunk to a twelfth of its size and enlarged to giant proportions, and a more responsible and intelligent race of beings inserted above (normally sized) humans) enable Swift to obtain critical normative distance from several major assumptions about politics, religion, aesthetics, ethics, and much more, including the limits of the thought experiment itself. In the second part of the paper, the impressivre use to which the Talmudic literature puts such imagined counterfactual scenarios, is examined, with special reference to ethics and law.

Nanocrystalline La_1-xNd_xFeO₃ powders with different concentrations of Nd³⁺ have been synthesized by modified Pechini method. Their structure was studied by X-ray powder diffraction (XRD). Further, La_1-xNd_xFeO₃ nanoceramics were prepared by high pressure sintering technique. The luminescence spectra of the powders were investigated as a function of concentration of active dopant to check the possible energy transfers observed due to Nd³⁺ concentration changes. The electrical and magnetic properties of the powders and ceramics were investigated to determine the effect of Nd³⁺ doping on the dielectric permittivity and magnetization in the wide frequency range.

Academic interest in social and human capital is growing significantly. Similarly, their relationship with sustainability is increasing, especially compared to sustainability’s relationship with natural capital and financial and economic capital. Bibliometric and visualization research on these relationships is nonetheless insufficient. This study analyzes the evolution of the literature on natural capital, financial and economic capital, and social and human capital related to sustainability. On the other hand, the study presents a bibliometric analysis on social capital and human capital (SHC) related to sustainability. The article studies 635 references collected from the Web of Science (WoS) Core Collection database and utilizes visualization of similarities (VOS) viewer program to graphically map the material. The analysis involves co-occurrence of keywords, co-citation, and co-authorship. The results reveal not only the state of the art and the leading trends, but also the evolution regarding impact, main journals, documents, topics, authors, institutions, and countries. The study provides researchers and practitioners with a visual and schematic frame of the research on this topic.

Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare neuroendocrine tumors characterized by catecholamine production in the adrenal medulla and extra-adrenal paraganglia. PPGL with metastasis was termed malignant PPGL. However, the distinction between “benign” and “malignant” PPGLs has been debated. Currently, all PPGLs are believed to have some metastatic potential and are assigned malignant tumors (ICD-O/3) by the WHO Classification of Endocrine Organs (2017, 4th edition). Therefore, the previous categories benign and malignant PPGL have been eliminated in favor of a risk stratification approach. The Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) is a tool for risk stratification for predicting metastasis and the prognosis of patients. At least 30% of PPGLs are hereditary, with 20 genes identified and genotype-phenotype correlations clarified. Of these, VHL, RET, and NF1 have been well investigated and are the primary cause of bilateral PCC. In addition, succinate dehydrogenase gene subunits SDHB and SDHD are strongly correlated with extra-adrenal location, younger age, multiple tumors, metastasis, and poor prognosis. Disease stratification by catecholamine phenotype and molecular profiling correlates with histological grading by GAPP. PPGLs should be understood comprehensively based on clinical, biochemical, molecular, and pathological data for patient care. A flow chart for pathological diagnosis is included.

Ghrelin and obestatin, two antagonist peptide hormones, are purportedly involved in stimulating appetite and controlling energy balance in humans. Serum ghrelin level is also associated with iron deficiency anemia (IDA), but no study has yet been made of the obestatin level in patients with IDA, even though both hormones are a single gene product. Therefore, the purpose of this investigation is to see whether there is a link between IDA and these two hormones among other hematological parameters in patients with IDA. To measure ghrelin and obestatin, human saliva and serum were collected from 30 women with IDA, aged 31.7 ± 10.7 years, and 30 control women, aged 30.2 ± 8.0 years, with repeated collection of samples over a period of 1 week and 1 month. Saliva and serum ghrelin levels were measured by ELISA. Serum hemoglobin, ferritin, hematocrit and total iron-binding capacity (TIBC) values were determined with an Olympus AU2700. Saliva and serum ghrelin and obestatin levels were significantly lower in the IDA group compared with controls; these levels increased slightly above baseline with iron treatment, but remained below the control values. Furthermore, and as expected, serum hemoglobin, ferritin, and hematocrit levels were significantly increased with iron treatment, while total iron-binding capacity decreased compared to baseline concentrations. The findings suggest that IDA might be linked to imbalance of circulating (serum) and non-circulating (saliva) ghrelin and obestatin levels. Decreased ghrelin and obestatin might destroy iron homeostasis through its effect on intestinal absorption. Measuring these hormone levels might be useful for monitoring the response to iron treatment. Also, serum and saliva levels for both hormones were well correlated. Thus, using saliva in place of serum for monitoring the two hormones should minimize inconvenience and patient discomfort.

Intermediate-luminosity-optical-transients (ILOTs) are stellar outbursts with luminosity between those of classical novae and supernovae. They are divided into a number of sub-groups depending on the erupting progenitor and the properties of the eruption. Many of the ILOTs sit on the slanted Optical Transient Stripe (OTS) in the Energy-Time Diagram (ETD) that shows their total energy vs. duration of their eruption. We describe the different kinds of ILOTs that populate the OTS and other parts of the ETD. We also stand on similarities between Planetary Nebulae (PN) to ILOTs, and suggest that some PNe were formed in an ILOT event. The high energy part of the OTS is reserved to the supernova impostors -- giant eruption of very massive stars. We show results of 3D hydrodynamical simulations of supernova impostors that expose the mechanism behind these giant eruptions, and present new models for recent ILOTs. We stand on the connection between different kinds of ILOTs, and suggest that they are powered by a similar source of energy -- gravitational energy released by mass transfer.

Alternative fuels available at low cost, friendly to natural environments and meet the energy needs and demands, have witnessed a growing demand and use today. Ethanol is an attractive renewable energy source with a high content of oxygen. Ethanol can be produced through ethanolisis, however for this work direct blending of conventional diesel, waste plastic pyrolysis oil and ethanol with commercial fuel improver CI-0808 purchased from Innospec company was attempted. The primary purpose of adding a cetane improver was to improve the combustion characteristics of the blends by at least 1- 3 ignition quality points. Five mixing ratios were chosen in the following order, 50:25:25, 60: 20:20, 70: 15:15, 80: 10:10 and 90: 5:5 for Waste Plastic Pyrolysis Oil (WPPO), ethanol and conventional diesel (CD) respectively. However, for the fuel additive mixing ratio the total volume percentage was considered and the ratio put at 0.01% of the total quantity of blended fuel. In this work WPPO, diesel blends and fuel additives improvers were used as alternative fuel. This was to evaluate their performance and emission characteristics in a stationary single cylinder water cooled experimental diesel engine. The CI-0808 was added due to its potential power to reduce emissions of CO, UHC, NO_X, PM and improved engine performance. The results obtained were compared carefully to ASTM standards and discussed using graph curves figures and tabulated values. The conclusion was that ethanol and WPPO blends can be used in diesel engines as alternative fuel without modification. Used in combination with cetane improvers the emissions reduce significantly and performance improved equalling that of conventional diesel fuel.

The present work is concerned with the study of the generalized Langevin equation and its link to the physical theories of statistical mechanics and scale relativity. It is demonstrated that the form of the coefficients of Langevin equation depend critically on the assumption of continuity of the reconstructed trajectory. This in turn demands for the fluctuations of the diffusion term to be discontinuous in time. This paper further investigates the connection between the scale-relativistic and stochastic mechanics approaches, respectively, with the study of the Burgers equation, which in this case appears as a stochastic geodesic equation. By further demanding time reversibility of the drift the Langevin equation can also describe equivalent quantum-mechanical systems in a path-wise manner. The resulting statistical description obeys the Fokker-Plank equation of the probability density of the differential system, which can be readily estimated from Monte Carlo simulations of the random paths. Based on the Fokker-Plank formalism a new derivation of the transient probability densities is presented. Finally, stochastic simulations are compared to the theoretical results.

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.

The effects of buckwheat intake on cardiovascular diseases (CVD) have not been systematically investigated. The aim of the present study was to comprehensively summarise studies in humans and animals evaluating the impact of buckwheat consumption on CVD risk markers and to conduct a meta-analysis of relevant data. Thirteen randomised, controlled human studies, two cross-sectional human studies and twenty-one animal studies were identified. Using random effects models, the weighted mean difference of post-intervention concentrations of blood glucose, total cholesterol and triglycerides were significantly decreased following buckwheat intervention compared with controls [differences in blood glucose: -0.85 mmol/L (95% CI: -1.31, -0.39), total cholesterol: 0.50 mmol/L (95% CI: -0.80, -0.20) and triglycerides: 0.25 mmol/L (95% CI: -0.49, -0.02)]. Responses of a similar magnitude were seen in two cross-sectional studies. For animal studies, nineteen of twenty-one studies showed a significant reduction in total cholesterol of between 12 and 54%, and fourteen of twenty studies showed a significant reduction in triglycerides of between 2 and 74%. All exhibited high unexplained heterogeneity. There was inconsistency in HDL cholesterol outcomes in both human and animal studies. It remains unclear whether increased buckwheat intake significantly benefits other markers of CVD risk, such as weight, blood pressure, insulin, and LDL-cholesterol, and underlying mechanisms responsible for any effects are unclear.

This paper addresses the atmospheric emissions from oil and gas extraction and production in Greece. The study was carried out in 2014 in the Kavala gulf, which currently is the only location of oil and gas production in Greece and where the exploration activities for hydrocarbons started in the late ‘60’s. This study presents the qualitative and quantitative characteristics of atmospheric emissions, in relation also to the emissions’ control management system. Particular reference is made to sulphur compounds since the existence of volcanic rocks results to increased amounts of H₂S. The results shows that, currently, atmospheric emissions of pollutants during extraction and production of hydrocarbons in Greece are very low and do not have any significant effect on air quality and climate change. Since it is expected that exploitation of hydrocarbons and oil and gas extraction and production will increase in the future, appropriate measures should be taken to ensure environmental protection, such as the development of integrated monitoring systems and the use of up to date emission control technologies.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

We explored the dynamics of the two interacting information systems. We show that for the Markovian marginal systems the driving force for information dynamics is determined by both the information landscape and information flux. While the information landscape can be used to construct the driving force to describe the equilibrium time reversible information system dynamics, the information flux can be used to describe the nonequilibrium time-irreversible behaviours of the information system dynamics. The information flux explicitly breaks the detailed balance and is a direct measure of the degree of the nonequilibriumness or time irreversibility. We further demonstrate that the mutual information rate between the two subsystems can be decomposed into the equilibrium time-reversible and nonequilibrium time-irreversible parts respectively. This decomposition of the mutual information rate (MIR) corresponds to the information landscape-flux decomposition explicitly when the two subsystems behave as Markov chains. Finally, we uncover the intimate relationship between the nonequilibrium thermodynamics in terms of the entropy production rates and the time-irreversible part of the mutual information rate. We found that this relationship and MIR decomposition still hold for the more general stationary and ergodic cases. We demonstrate the above features with two examples of the bivariate Markov chains.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-кB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-кB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-кB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-кB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-кB crosstalk.

The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This study provides the methodological foundation for the prospective CONCORDIA trial, which will generate this data for the first time. In this preliminary work, we evaluated the proposed measurement tool for the CONCORDIA study -the System-Causability-Scale (SCS) and its modified version (mSCS) - based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer-scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen’s K &gt; 0.74), and internal consistency (all Cronbach’s Alpha &gt; 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p&lt;0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.

Background: Immune evasion in cancer is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Recent developments have immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy effectively impede this process but benefit a limited patient cohort. This investigation introduces a systemic immunotherapeutic strategy by inhibition of master-regulators of immune evasion (MR-IE). Methods: We utilized the TCGA PanCancer Atlas transcriptomic data to subset and stratify cancer samples based on IC expression levels and CIBERSORT to estimate immune cell infiltration. Differential gene expression analysis was conducted to unravel pathways associated with the immune evasion. Transcription Factor Enrichment Analysis and Survival Analysis was conducted to identify and rank candidate MR-IE per cancer type. The top-ranking candidate MR-IE of cholangiocarcinoma (CCA) was validated for its regulation of ICs using quantitative PCR and western blots. Orbitrap Proteomics was employed to assess changes in the immune-related proteome of CCA cells after MR-IE is inhibited or knocked-down. Lastly, CCA cell viability and immune-mediated cell death was assessed after MR-IE inhibition in combination with fourth-generation anti-folate receptor alpha (FRɑ) CAR-T cell therapy. Results: This workflow ranked and identified candidate MR-IE for 33 tumor types. MYC was identified as the high-ranking candidate MR-IE for CCA. MYC modulated PD-L1 expression adn key markers of inflammation and IC expression in CCA cells. Moreover, MYC inhibition was able to potentiate CAR-T mediated cell death in CCA cells. Conclusions: Cumulatively, these results offer a candidate list of MR-IE immunotherapeutic targets per cancer type that can be further explored and validated. This study also highlights the promise of MR-IE inhibition as a novel potent immunotherapeutic strategy for the treatment of CCA.

The rapid urbanization process in recent decades has altered the carbon cycle and exacerbated the impact of climate change, prompting many cities to develop tree planting and green area preservation as mitigation and adaptation measures. While numerous studies have estimated the carbon stocks of urban trees in temperate and subtropical cities, data from tropical regions, including tropical botanic gardens, are scarce. This study aimed to quantify the aboveground biomass and carbon (AGB and AGC, respectively) stocks in trees at the Rio de Janeiro Botanical Garden arboretum, Rio de Janeiro, Brazil. Our survey included 6793 stems with a diameter at breast height (DBH) ≥ 10 cm. The total AGB was 8,047.24 Mg, representing 4,023.62 Mg of AGC. The AGB density was 207.4 Mg.ha-1 (AGC = 103.7 Mg.ha-1), which is slightly lower than the density stored in Brazil's main forest complexes: the Atlantic and Amazon forests, but much higher than in many cities worldwide. Our results suggest that, in addition to their global importance for plant conservation, tropical botanic gardens could function as significant carbon sinks within the urban matrix.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

We consider spontaneous quark transitions between the Λ0 baryon and its resonant states, and (anti)quark transitions between the neutral kaon K0 and the two heavy ηq-mesons (q = c, b). We use the measured differences in mass deficits to calculate the binding energy levels of valence c and b (anti)quarks in these transitions. In the process, we account for isospin energy release in K0 transitions and for the work done by the strong force in suppressing Coulomb repulsions in the charged Λc+-baryon. We find that the flips s→c and s¯→c¯ both release energy back to the strong field; and that the overall range of quark energy levels above their u-ground is 100-MeV wider than that of antiquark energy levels above their d¯-ground. The wider quark range stems from the flip s→b, which costs 283 MeV more (or 3× more) than the corresponding antiquark flip s¯→b¯. At the same time, transitions from the respective ground states to the s and s¯ states (or the c and c¯ states) point to a clear origin of the elusive charge-parity (CP) violation. The determined binding energy levels of (anti)quarks allow us to analyze in depth the (anti)quark transitions in Λ-baryons and B-mesons.

Surfing is a growing, high participation recreational and competitive activity. It is relatively unique being performed on, in, and through water with a range of temperatures. In other sports, warm-up and heat retention have proved useful at augmenting performance and ameliorating injury risk. Little work has been done examining this in surfing. The purpose of this work was to measure thermal profiles in surfers with and without warm-up and passive heat retention, and secondarily to assess any potential influence on free surfing. A repeated measures pre- and post- design was adopted whereby participants surfed in an artificial wave pool following an active warm-up combined with passive heat retention (experimental condition), and after no warm-up (control). Core body temperature was measured both occasions. Our results showed a clear advantage to body temperature for the experimental condition versus control. Both groups showed a warm-up effect in the water itself, presumably due to further activity (e.g. paddling) and wetsuit properties. Finally, performance trended to being superior following warm-up. We conclude, body warmth in surfers may be facilitated by an active warm-up and passive heat retention. In free surfing this is associated with a trend towards better performance; it may also reduce injury risk.

During our digital transition, Docker containers have become essential for adaptable application deployment, although posing inherent security threats. This study utilizes Trivy for static analysis and Falco for dynamic analysis to identify and address vulnerabilities in Docker environments before deployment and in real-time. The IoT sector is now dealing with security issues that are made more severe by extensive connectivity and the prevalence of WiFi. This research promotes the use of AWS cloud security technologies such as IoT Core, CloudWatch, and GuardDuty to protect IoT devices from threats, with the goal of maintaining user privacy and ensuring safety in our interconnected digital world. This comprehensive strategy aims to enhance security measures in both Docker and IoT sectors, strengthening the security framework in our interconnected world.

Some evidence supports the influence of the implant macro-design and primary stability. Additionally, tactile perception can be used to assess implant stability when placing the implant. This research aimed to quantify the primary and secondary stability of three implant systems with two different macro geometries (cylindrical and conical) determined through the insertion torque and the implant stability quotient (ISQ) at the moment of implant placement as a function of implant-related factors (length, width, dental arch, and implant location in the arch), intraoperative factors (bone density determined subjectively by the clinician's tactile perception), and patient-related factors (age, gender and bone density determined objectively in the cone beam computed tomography (CBCT). Methods: 102 implants of three implant systems with two different macro geometries (conical and cylindrical) were placed in 53 patients. The insertion torque, the ISQ at the implant placement (ISQ0), and bone quality according to the clinician's tactile sensation were recorded on the day of the surgery. After a three-month healing period, the ISQ was re-evaluated (ISQ3). Results: Cylindrical implants exhibited significantly higher insertion torque and ISQ at the moment of the surgery and after three months than conical implants. Cylindrical implants also showed significantly lower indices of tactile evaluation of bone quality during the implant placement surgery. However, no differences were demonstrated in the bone density measured objectively in the CBCT. (4) Conclusions: The cylindrical implants achieved the highest values for primary stability (Ncm and ISQ) and secondary stability (ISQ after three months). Insertion torque was the variable that most influenced ISQ on the day of the surgery. Implant location (incisors-canines, bicuspids-molars) and the implant macro geometry were the variables that most influenced the secondary stability (ISQ at three months).

Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics chamazulene is exploited as a natural coloring and soothing agent. CA is unstable and tends to spontaneous degradation accelerated by light. We studied the photodegradation of CA upon controlled exposure to UVB-UVA irradiation by multi-ple techniques, including GC-MS, UHPLC-PDA-ESI-MS/MS and by direct infusion in ESI-MSn, which were matched to in silico mass spectral simulations to identify degra-dation products. Seven byproducts formed upon UVA exposure for 3 h at 70mW/cm2 (blue-to-green color change) were identified, including CA dimers and CA benzenoid which were not found on extended 6 h irradiation (green-to-yellow fading). Photosta-bility tests with reduced irradiance conducted in various solvents in the pres-ence/absence of air indicated highest degradation in acetonitrile in the presence of ox-ygen, suggesting a photo-oxidative mechanism. Testing in the presence of antioxidants (tocopherol, ascorbyl palmitate, hydroxytyrosol, bakuchiol, γ-terpinene, TEMPO and their combinations) indicated highest protection by tocopherol and TEMPO. Sun-screens ethylhexyl methoxycinnamate and particularly Tinosorb® S (but not octo-crylene) showed good CA photoprotection. Thermal stability tests indicated no degra-dation of CA in acetonitrile at 50°C in the dark for 50 days; however, accelerated deg-radation occurred in the presence of ascrorbyl palmitate.

Two new Mn(II) and Zn(II) metal-organic compounds of 1,10-phenanthroline and methyl benzoates viz. [Mn(phen)2Cl2]2-ClBzH (1) and [Zn(4-MeBz)2(2-AmPy)2] (2) (where, 4-MeBz = 4-methylbenzoate, 2-AmPy = 2-aminopyridine, phen = 1,10-phenanthroline, 2-ClBzH = 2-chlorobenzoic acid) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FTIR, electronic) and single crystal X-ray diffraction techniques. Crystal structure analysis of the compounds reveals the presence of various non-covalent interactions which provides stability to the crystal structures. Crystal structure analysis of the compound 1 reveals the formation of supramolecular dimer of 2-ClBzH enclathrated within the hexameric host cavity formed by the neighboring monomeric units. Compound 2 is a mononuclear compound of Zn(II) where flexible binding topologies of 4-CH3Bz is observed with the metal centre. Moreover various non-covalent interactions such as lp(O)-π, lp(Cl)-π, C‒H∙∙∙Cl, π-stacking interactions as well as N‒H∙∙∙O, C‒H∙∙∙O and C‒H∙∙∙π hydrogen bonding interactions are found to be involved in plateauing the molecular self-association of the compounds. The remarkable enclathration of the H-bonded 2-ClBzH dimer into a supramolecular cavity formed by two [Mn(phen)2Cl2] complexes has been further studied theoretically using density functional theory (DFT) calculations, non-covalent interaction (NCI) plot index and quantum theory of atoms in molecules (QTAIM) computational tools. Synergistic effects have been also analysed using molecular electrostatic potential (MEP) surface analysis.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

The present study evaluated the antioxidant, antidiabetic properties, and biocompatibility of Medicago sativa and Solidago virgaurea extracts enriched in flavonoid and isoflavonoid compounds. The extracts were obtained by accelerated solvent extraction and laser irradiation. Then, nanofiltration was used for the concentration of flavonoid and isoflavonoid compounds from extracts. The extracts were analyzed for antioxidant capacity using DPPH radical scavenging and reducing power methods, while the antidiabetic property was tested by α-amylase and α-glucosidase inhibition and in vitro on a murine insulinoma cell line (β-TC-6). M. sativa obtained by laser irradiation and concentrated by nanofiltration had the highest DPPH• scavenging (IC50 = 105.2±1.1 and reducing power activities (IC50 = 40.98±0.2 µg/mL). M. sativa extracts had higher inhibition on α-amylase (IC50 = 23.9±1.2, respectively 26.8±1.1), while S. virgaurea had the highest α-glucosidase inhibition (9.3±0.9 ?g/mL respectively 8.6±0.7 ?g/mL). The results obtained after evaluating the antidiabetic in vitro activity showed that the treatment with M. sativa and S. virgaurea flavonoid- and isoflavonoid-rich extracts stimulated the insulin secretion of β-TC-6 cells, both under normal conditions as well as in hyperglycemic conditions. This paper argued that M. sativa and S. virgaurea flavonoid-rich and isoflavonoid-rich extracts could be an excellent natural source with promising antidiabetic potential.

Herein are reported the main pros and cons of using the conversational Artificial Intelligence (AI) called “ChatGPT” as a tool to write essays in the academic and scientific community. Also, selected mathematical and scientific problems were solved to determine the effectiveness of this platform. To this end, a systematic case study was designed and conducted to obtain data generated by the chatbot that was further analyzed. Six different topics were chosen for the essay evaluation, and the introduction section was created using this AI. Meanwhile, six mathematical problems related to integrals, z-transform, Laplace transform, and resolution of ordinary differential equations were solved. Furthermore, a scientific problem associated with the structural properties of material was also solved. After data analysis, we concluded that the conversational platform could quickly create written essays with well-structured words. Nonetheless, in almost all cases, the chatbot only used basic information to complete the introduction, and no critical writing was obtained. For the mathematical case study, we observed that under the current status of the ChatGPT, this platform has no ability or skills to solve complex equations. Thus, significant changes need to be conducted to improve the performance of ChatGPT for mathematical solutions.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

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

Tribological testing of moving shaft/sealing pairs in complex environments is at the frontline of research. Machines working in abrasive conditions are subject to different wear effects. It is valid not only on the Earth but especially valid for rovers and future robots used in Mars and Moon missions. The aim of our joint research with the European Space Agency is to study the abrasion phenomena of moving machine elements on Mars and the Moon, by using artificial soil samples (“simulants”). This review detail the available simulant sources and recommend a selection of the most suitable ones for tribological testing. Moreover, the potential mating structural materials subjected to abrasive space applications are reviewed. The tribological tests are exploring the features of the rotary shaft/seal relationship that is subject to dry friction and intense abrasion. By using the simulants, measurements are performed under laboratory conditions with both a sample test and a real shaft/seal connection. Parameters of the selection criteria have been defined and classification of the simulant sources were made. It was found that simulant particle size distribution and chemical substance content is detailed enough only for a limited type of available artificial Moon and Mars soil samples. 4 simulants have been identified and applied later in the tribological testing. For the shaft materials, based on a detailed case study of polymers, steel and aluminium alloys, a high-strength aluminium alloy with a hard anodized surface and a stainless steel were selected for further abrasion tests.

China promotes nature-based solutions (NbS) as key approaches to addressing climate change, ecosystem damage, and biodiversity loss. However, indigenous and local knowledge (ILK), which is recognized by international scholars as an essential element of successful NbS, has not been thoroughly studied in the Chinese context. By conducting a comprehensive review of Chinese central governmental policies and semi-structured interviews with typical cases, this study finds out diversified sources of ILK and five pathways of ILK integration, including education, supervision, participation, knowledge preservation, and knowledge adoption. An increasing emphasis on community engagement has been driven by central policies such as the ecological civilization, carbon peaking and carbon neutrality goals. From a practical perspective, consistent core ideas of ILK exist in selected typical Chinese cases and studies in other countries, namely co-existence and reciprocity with nature. While supportive central policies can set the scene, ILK integration could not be realized without local governmental endorsement, context-based implementation, and long-term multi-stakeholder participation. Furthermore, this study also figures out a potential deficiency in terms of realizing effective ILK integration in mainstream and conventional practices, which can be further investigated by future studies.

Stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V exhibit properties for bio-medical applications; however their tribocorrosion associated with metallosis is still a major concern. Therefore smoothing DLC coatings aiming for the improvement of tri-bocorrosion and cell viability of stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V with and without DLC coatings were compared. The motivation was due to many papers detailing metallosis caused by metal debris in the body's soft tissues. Nowadays, metallosis is responsible for almost of prosthesis replacement surgeries. DLC coatings were produced using the Plasma Enhanced Chemical Vapor Deposition (PECVD) technique; acetylene gas was used as a carbon precursor, and silane gas produced an amorphous silicon interface between the DLC coating and metal substrate. A combined setup of techniques thoroughly evaluated the coatings considering chemical composition, coatings adhesion at a metallic substrate, scratch resistance, and tribocorrosion susceptibility. The cytotoxicity and genotoxicity of metallic samples with and without DLC coatings were analyzed, considering cell viability and its correlation with coatings’ chemical composition

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%), and in 15% of cases, the primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques, and early detection have shown improvement in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of Gastrointestinal and pancreatic (GEPs) NETs grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed, and pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. The forest plots were created using random-effects models and sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusion: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve mortality.

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.

Using density functional theory (DFT) and the information-theoretic approach (ITA) quantities to appreciate the energetics and properties of biopolymers is still an unaccomplished and ongoing task. To this end, we studied the building blocks of nucleic acid base pairs and small peptides. For base pairs, we have dissected the relative importance of energetic components by using two energy partition schemes in DFT. Our results convincingly show that the exchange-correlation effect predominantly governs the molecular stability of base pairs while the electrostatic potential plays a minor but indispensable role, and the steric effect is trivial. Furthermore, we have revealed that simple density-based ITA functions are in good relationships with molecular polarizabilities for a series of 30 hydrogen-bonded base pairs and all 20 natural α-amino acids, 400 dipeptides, and 8000 tripeptides. Based on these lines, one can easily predict the molecular polarizabilities of larger peptides, even proteins as long as the total molecular wavefunction is available, rather than solving the computationally demanding coupled-perturbed Hartree-Fock (CPHF) equation or its DFT counterpart coupled-perturbed Kohn-Sham (CPKS) equation.

Erosion caused by the repeated impact of particles on a substance surface is a usual wear method resulting in gradual and continual loss of objects. It is a crucial problem in several modern industries because their surfaces are frequently subjected to destructive erosive situations. Polymers and their hybrid materials include several applications to be used as a coating in the form of powder for different applications. This review paper aims to provide extensive information on the erosion behavior of thermoset and thermoplastic neat resin and their hybrid materials composites. Focus is specifically paid to highlight the influence of properties of selected materials, impingnation parameters such as incident Angle of erodent, impact velocity of erodent, erodent nature, and the erosion mechanism. The review further extends the information about the erosion techniques and numerical simulation methods used for wear studies of surfaces. An investigation has been carried out for researchers to explore the selection of materials and methods in terms of conditions and parameters to meet the current and future needs and challenges for the protection of surfaces of the advanced industries. During review according to the findings achieved from the literature of the past fifty years, it has been noted that the thermoplastic nature of the composite is a key component to determine the anti-wear properties, the composites with lower glass transition, higher ductility, and greater crystallinity can provide better protection to erosion in advance surface applications.

The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). “Superwobbling” or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.

Meat tenderness, water holding capacity (WHC) and colour attributes of six muscles (Longissimus thoracis et lumborum (LTL), Semimembranosus (SM), Biceps femoris (BF), Supraspinatus (SS), Infraspinatus (IS), Semitendinosus (ST)) from large frame Indigenous Veld Goats (IVG) and Boer Goats (BG) were studied. Weaner male Boer Goats (BG; n = 18; 10 bucks and 8 wethers) and large frame Indigenous Veld Goats (IVG; n = 19; 9 bucks and 10 wethers) were raised on hay and natural grass, and on a commercial pelleted diet to a live weight of 30 - 35 kg. All goats were slaughtered at a commercial abattoir and the dressed carcasses chilled at 4°C within 1-hour post-mortem. The muscles were dissected from both sides 24-hours post-mortem and aged for 1-day and 4-days. Variations in meat characteristics such as ultimate pH, WHC, percentage purge, myofibril fragment length, intramuscular fat, connective tissue characteristics, and Warner-Bratzler shear force. Bucks had higher L* and Hue-angle values, whereas wethers had increased a* and Chroma values. The muscle baseline-data will allow informed decisions to support muscle-specific marketing strategies, which may be used to improve consumer acceptability of chevon.

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There are no data whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS pathways (SMD: 0.796; CI: 0.503; 1.089), an immune-inflammatory response (SMD: 1.409; CI: 0.637; 1.462), inflammation (SMD: 1.200; CI: 0.584; 1.816), and neurotoxicity (SMD: 0.904; CI: 0.431; 1.378). The effects sizes of the IO&NS, immune-inflammatory response and inflammatory profile were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection may explain at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.