The acquisition of regional, 1 metre resolution LIDAR in the PNG Highlands combined with 3D modelling in MoveTM has revolutionized our understanding of the evolution of the Porgera gold mine and areas of new potential. The new 3D model demonstrates active pull-apart basins along a regional transfer during ongoing fold and thrust deformation. When overlain on regional aeromagnetic data, new potential is revealed. The Porgera gold mine is one of the richest in the world and lies in a wide valley at an elevation of 2800m surrounded by mountains up to 4000m high in the middle of the PNG Highlands. It lies along a major lineament, the Porgera Transfer Zone (PTZ), cutting across the orogen that is associated with a 50 km offset of the ophiolite belt. To the NW of the mine there is an extensive belt of low- to high-grade metasediments that formed in deep water during Jurassic rifting, but were metamorphosed during Eocene subduction to the north. Subduction ceased due to accretion of the Sepik Terrane which caused inversion and mild erosion of the Porgera area. The Late Oligocene onset of wrenching in the Mobile Belt to the north placed that area into extension, emplacing metamorphic core complexes, and led to regional subsidence in the Early Miocene. Collision of the margin with the Melanesian Arc in the Middle Miocene caused Late Miocene to Pliocene orogenesis creating the broad mountain belt that we see today, that is still active, as shown by the 2018 MW 7.5 earthquake. Regional mapping of the area using high resolution LIDAR in association with limited field mapping, analysis of gravity and magnetics data and drilling of 300-500m deep core-holes has allowed development of a detailed 3D structural model. The Porgera valley is constrained laterally by the Eastern Boundary and Western Boundary dextral strike-slip faults that lie along the PTZ cutting across the orogeny. However, whilst the position and nature of the faults is clear, due to bending, fracturing and offset of major synclines and anticlines, the faults do not crop-out as significant through-going features. Rather, the dextral offset of basement is soft-linked to the Tertiary limestones at surface due to intervening thick, ductile Cretaceous shales. Fold and thrust structures are ubiquitous in the Tertiary limestones, but the youngest structural features are large extensional faults, particularly around the Porgera valley. The intrusive underlying the Porgera ore-body was emplaced at 6.0+-0.3 Ma, the time of maximum compression during orogenesis. At this time the Eastern Boundary fault and Western Boundary fault were both active allowing a pull-apart basin to form locally along the PTZ at the south-eastern boundary of the Jurassic metasediments. This enabled emplacement of the intrusive. The gold-bearing fluids from the intrusive and metasediments were brought up through the Mesozoic muds to the contact with the Paleogene carbonates where the Porgera ore body was emplaced.

Many cancers utilize L-glutamine as a major energy source. This “L-glutamine addiction” involves a well-characterized pathway whereby L-glutamine is hydrolyzed by a glutaminase (GLS) to L-glutamate, which is then converted to α-ketoglutarate, the carbons of which enter the tricarboxylic acid (TCA) cycle. However, mammalian tissues/cancers possess a rarely mentioned alternative pathway (the glutaminase II pathway): L-Glutamine is transaminated to α-ketoglutaramate (KGM), followed by ω-amidase (ωA)-catalyzed hydrolysis of KGM to α-ketoglutarate. Uncertainty may prevail over the name glutaminase II which may be confused with the enzyme named glutaminase 2 (GLS2). Thus, we recently suggested a new name for the glutaminase II pathway, namely the glutamine transaminase-ω-amidase (GTωA) pathway. Herein, we 1) evaluate three recent articles that mention L-glutamine addiction, but not the GTωA pathway, 2) summarize the metabolic importance of the GTωA pathway, including its role in closing the methionine salvage pathway, and 3) as a source of anaplerotic α-ketoglutarate. An advantage of the GTωA pathway [i.e., L-glutamine + α-keto acid + H2O α-ketoglutarate + L-amino acid + +NH4] is that it is irreversible and that there is no net change in redox status, permitting α-ketoglutarate production during hypoxia. Finally, we discuss possible clinical benefits of GTωA pathway inhibitors.

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Although many small molecules have been proposed as inhibitors of amyloid formation, few have been successful in clinical trials. Amyloid formation is complex and several individual steps could be targeted by small molecules. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light chain dimers, the precursor proteins for AL amyloidosis are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidogenesis.

This paper has three objectives, the first is to present a detailed overview in the form of a tutorial for the developments of several key quantile time series modelling approaches. The second objective is to develop a general framework to represent such quantile models in a unifying manner in order to easily develop extensions and connections between existing models that can then be developed to further extend these models in practice. In this regard, the core theme of the paper is to provide perspectives to a general audience of core components that go into construction of a quantile time series model and then to explore each of these core components in detail. The paper is not addressing the concerns of estimation of these models, as there is existing literature on these aspects in many settings, we provide references to relevant works on these aspects in several classes of model. Instead, the focus is rather to provide a unified framework to construct such models for practitioners, therefore the focus is instead on the properties of the models and links between such models from a constructive perspective. The third objective is to compare and discuss the application of the different quantile time series models on several sets of interesting demographic and mortality based time series data sets of relevance to life insurance analysis. The exploration included detailed mortality, fertility, births and morbidity data in several countries with more detailed analysis of regional data in England, Wales and Scotland.

This research hypothesised that the use of Virtual Reality (VR) applications can be used to train people in the ability to acquire targets faster, with greater accuracy when using motion controllers than compared with a traditional pointing device (mouse) on a 2D display. User performance was defined and measured using Reaction Time and Accuracy. The research findings suggests that the use of motion controllers in VR improved Reaction Time but not Accuracy when compared against the traditional pointing device and 2D display. This suggests that VR can be used specifically in training scenarios where Reaction Times are more important than Accuracy. It is recommended that further research is conducted using a wider range of hardware and software configurations with a stratified sample that takes into account age and gender to expand the collective understanding of factors that impact on VR aiming and target acquisition in VR.

We suppose that a Cooper pair (CP) will experience a damping force exerted by the condensed matter. A Langevin equation of a CP in two dimensional condensed matter is established. Following a method similar to Nelson's stochastic mechanics, generalized Schr\"{o}dinger equation of a CP in condensed matter is derived. If the CPs move with a constant velocity, then the corresponding direct current (DC) electrical conductivity can be calculated. Therefore, a Drude like formula of resistivity of CPs is derived. We suppose that the damping coefficient of CPs in two dimensional cuprate superconductors is a linear function of temperature. Then the resistivity and scattering rate of CPs turn out to be also linear-in-temperature. The origin of linear-in-temperature resistivity and Planckian dissipation in cuprate superconductors may be the linear temperature dependence of the damping coefficient of CPs.

The novelty of this study consists in: i) synthesis and characterization of electrode materials recycled from a spent car battery and doped with MnO2 and CuO by the analysis of X-ray diffraction (XRD), Infrared (IR) and Electron Paramagnetic Resonance (EPR) data and ii) the investigation of electrochemical properties of prepared materials in view of new applications as electrode materials for battery. Electron Paramagnetic Resonance (EPR) data indicate that the intensity of the resonance line corresponding to the Cu+2 ion was modified with the increase of the dopant content. The analysis of X-ray Absorption Spectroscopy (XAS) data indicates that by increasing the dopant content there is a process of ordering the oxygen atoms around the lead similar to the PbO2 theoretical model. The electrochemical performances of the recycled and manganese-copper-doped materials are optimized for applications as new anodic electrode for the car battery.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

This qualitative research explores negotiation dynamics within procurement, focusing on strategies, challenges, and outcomes in contemporary business environments. Negotiation in procurement plays a crucial role in shaping organizational strategies, supplier relationships, and operational efficiencies. In a globalized economy characterized by rapid technological advancements and market uncertainties, effective negotiation practices are essential for organizations seeking competitive advantage and sustainable growth. Through semi-structured interviews with procurement professionals, supply chain executives, and industry experts, this study examines the nuanced strategies employed in negotiation processes. Thematic analysis of the data reveals key themes including negotiation strategies (e.g., preparation, flexibility), challenges (e.g., price volatility, regulatory constraints), and outcomes (e.g., cost savings, innovation incentives). Relationship management emerges as pivotal, highlighting the importance of trust, transparency, and mutual respect in fostering collaborative supplier partnerships. The study also explores contextual factors (e.g., organizational culture, industry dynamics) and emotional dimensions (e.g., emotional intelligence, interpersonal dynamics) that influence negotiation effectiveness.

Supplier collaboration and partnership in procurement are essential elements for enhancing organizational efficiency, innovation, and resilience in today's globalized markets. This qualitative study investigates the dynamics of effective supplier relationships, focusing on trust, communication, innovation, quality, cost savings, and resilience as critical factors. Data were gathered through semi-structured interviews, case studies, and document analysis across diverse industries, highlighting insights from procurement professionals and supplier representatives. Key findings underscore the foundational role of trust and communication in fostering successful collaborations. Establishing transparent, ongoing communication channels facilitates mutual understanding, reduces conflicts, and enhances overall satisfaction. Collaborative innovation emerged as pivotal, enabling organizations to pool resources and expertise for product development and process improvement. Quality and reliability were identified as significant outcomes of close partnerships, particularly in industries with stringent standards such as aerospace and healthcare. Furthermore, the study reveals substantial cost savings and efficiency gains through collaborative efforts in process optimization and waste reduction. Effective risk management practices within these partnerships enhance supply chain resilience, enabling organizations to anticipate and mitigate disruptions proactively. Despite these benefits, challenges such as cultural differences, technological integration, and regulatory compliance require strategic mitigation strategies. In conclusion, organizations can optimize supplier collaborations by prioritizing trust-building, fostering a culture of innovation, and investing in robust relationship management practices. This approach not only enhances operational performance but also positions organizations to navigate market uncertainties and achieve sustainable growth in a competitive landscape.

Implementing ethical procurement standards is increasingly recognized as pivotal for organizations aiming to align their practices with principles of social responsibility and sustainability. This qualitative research explores the experiences, challenges, strategies, and impacts associated with ethical procurement across diverse sectors. Motivations for adopting ethical procurement include enhancing corporate reputation, meeting stakeholder expectations, and complying with regulatory frameworks. However, organizations face significant challenges such as balancing ethical considerations with cost-efficiency pressures, navigating complex regulatory landscapes, and ensuring transparency across global supply chains. Strategies for overcoming these challenges emphasize effective supplier relationship management, leveraging technological innovations for transparency, and investing in supplier capacity-building. The study reveals that ethical procurement practices contribute to organizational resilience by improving risk management, enhancing stakeholder engagement, and fostering innovation in procurement processes. Moreover, ethical procurement supports sustainable development goals by promoting environmental sustainability, supporting social equity through fair labor practices, and contributing to economic development. Future research directions include exploring the impact of emerging technologies on ethical procurement, promoting global collaboration for unified standards, and evaluating the long-term sustainability of ethical procurement initiatives.

This qualitative study explores the challenges and successes in supplier development from the perspectives of procurement managers across diverse industries. Through in-depth interviews, key themes emerged, highlighting the critical role of communication, trust, performance measurement, capacity building, risk management, innovation, regulatory compliance, and technology integration in supplier relationship management. Procurement managers emphasized the importance of clear, continuous communication and trust-building activities to align objectives and foster collaborative partnerships. Performance measurement was crucial for evaluating and improving supplier performance, supported by capacity-building initiatives to enhance supplier capabilities. Risk management strategies focused on identifying and mitigating risks, while compliance efforts aimed to ensure adherence to industry standards. Innovation and technological integration were pivotal for driving efficiency and competitiveness, enabling faster time-to-market and improved product quality. Cultural sensitivity and relationship strengthening emerged as essential for navigating diverse cultural contexts and enhancing partnership effectiveness. Overall, the findings underscored positive outcomes including enhanced quality, cost efficiencies, and increased resilience within supply chains. This research contributes valuable insights into effective supplier management practices, emphasizing the strategic importance of supplier development initiatives for sustainable growth and competitive advantage in today's dynamic business environment.

This qualitative research investigates sustainable procurement practices, focusing on the integration of environmental and social criteria in supplier evaluation processes. The study explores how organizations, ranging from large multinational corporations to smaller enterprises, navigate sustainability challenges and opportunities within their procurement strategies. Data were gathered through semi-structured interviews with procurement professionals and sustainability managers across diverse industries. Themes identified include varying organizational commitments to sustainability, from structured policies and resource allocation in larger firms to reactive approaches constrained by resource limitations in smaller entities. Effective supplier relationship management emerged as crucial, facilitating collaborative partnerships aimed at improving environmental and social performance across supply chains. Motivations for sustainable procurement practices encompass regulatory compliance and responding to consumer demands for eco-friendly products, shaping procurement decisions to enhance market competitiveness and stakeholder satisfaction. Environmental and social criteria integration in supplier evaluations highlighted strategies such as lifecycle assessments and sustainable sourcing practices, aimed at minimizing environmental footprints and promoting ethical labor practices. Benefits included cost savings and enhanced brand reputation, tempered by challenges such as higher procurement costs and supplier resistance. Leadership commitment and organizational culture were identified as critical enablers of sustainable procurement, influencing strategic alignment and fostering a culture of sustainability within organizations. The study underscores the transformative potential of sustainable procurement in achieving organizational resilience and contributing to global sustainability goals.

Agile procurement has emerged as a transformative strategy for organizations striving to maintain competitiveness in a rapidly evolving marketplace. This qualitative research investigates the implementation, benefits, challenges, and outcomes of agile procurement practices in supply chain management. Through semi-structured interviews and case studies across diverse industries, this study explores how agile procurement enhances organizational adaptability and responsiveness. Key findings reveal that agile procurement enables organizations to swiftly adjust strategies in response to market fluctuations and customer demands, fostering increased customer satisfaction and loyalty. The integration of advanced technologies, including AI and blockchain, facilitates real-time data analysis, optimizing procurement processes and enhancing supply chain efficiency. Organizational culture emerges as a critical factor in successful agile procurement, with leadership support and a collaborative environment driving cultural change towards agility and innovation. Despite its benefits, challenges such as resistance to change and the need for significant technology investments are identified, requiring careful change management and strategic alignment. Case studies illustrate the versatility of agile procurement across sectors, showcasing its role in enhancing operational efficiencies, innovation capabilities, and overall supply chain performance. In conclusion, agile procurement offers organizations a strategic framework to navigate complexities and uncertainties effectively, capitalizing on market opportunities while mitigating risks. Embracing agile principles fosters a resilient organizational culture capable of adapting to dynamic market conditions. Future research should focus on further refining agile procurement strategies to address emerging challenges and sustain competitive advantage in the global marketplace.

Accurate evaluation of health status of lithium-ion batteries must be deemed as of great significance, insofar as utility and safety of batteries are of concern. Lithium plating, in particular, is notoriously known to be a chemical reaction that can cause deterioration in, or even fatal hazards to, the health of lithium-ion batteries. Electrochemical impedance spectroscopy (EIS), which has distinct advantages such as fast or non-destructive over its competitors, suffices in detecting lithium plating and thus has been attracting increasing attention in the field of battery management, but its ability of assessing quantitatively the degree of lithium plating remains largely unexplored hitherto. On this point, this work seeks to narrow that gap, by proposing an EIS-based method that can quantify the degree of lithium plating. The core conception is to eventually circumvent the reliance on state-of-health measurement, and use instead the impedance spectrum, to acquire an estimate on battery capacity loss. To do so, the effects of solid electrolyte interphase formation and lithium plating on battery capacity must be first decoupled, so that the mass of lithium plating can be quantified. Then, based on an impedance spectrum measurement, the parameters of the fractional equivalent circuit model (ECM) of the battery can be identified. These fractional ECM parameters are received as inputs by an artificial neural network, which is tasked to establish a correspondence between the model parameters and the mass of lithium plating. The empirical part of the work revolves around the data collected from an aging experiment, and the validity of the proposed method is truthfully attested by dismantling the batteries, which is otherwise not needed during the actual uptake of the method.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Abstract Epilepsy is a disorder of the brain and a seriously debilitating condition, which has been associated with injury, social stigmatisation and in some cases, sudden unexpected and premature death. A sense of profound isolation is felt by many individuals with epilepsy, and this community has expressed an urgent desire for an early warning system to allow them time to prepare for seizure onset. Surveys of dog owners with epilepsy have previously reported that some dogs can predict the onset of a seizure. The current study used an experimental design to investigate the alleged propensity of untrained pet dogs to react to human epileptic seizures. We hypothesised that seizures are associated with specific volatile organic compounds resulting in detectable odours which are the biomarker that triggers these reported behavioural changes in the dogs. Here we provide details of the first empirical test to demonstrate that pet dogs display several significant behavioural changes when they are exposed to seizure-related odours that apparently emanate from their owners. Using a repeated measures design experiment, recordings were made of the reactions of 19 untrained pet dogs to odours from sweat samples provided by three people with epilepsy and by two people without epilepsy (controls). The seizure-associated sweat samples were captured pre-seizure, during seizure and post-seizure. All samples were randomly delivered to individual dogs in a test area, using two bespoke pieces of apparatus called Remote Odour Delivery Mechanisms (RODM). One RODM delivered only experimental odours, the other delivered only control odours. Behavioural changes by the dogs on encountering the odour samples were recorded by video for later analysis. Consistent with our hypothesis, seizure-associated odours evoked significant behavioural changes in the dogs which were affiliative in nature and directed at their owners.

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

A class of models for non-Gaussian spatial random fields is explored for spatial field reconstruction in environmental and sensor network monitoring. The family of models explored utilises a class of transformation functions known as the Tukey g-and-h transformations to create a family of warped spatial Gaussian process models which can support various desirable features such as flexible marginal distributions, which can be skewed, leptokurtic and/or heavy-tailed. The resulting model is widely applicable in a range of spatial field reconstruction applications. To utilise the model in applications in practice, it is important to carefully characterise the statistical properties of the Tukey g-and-h random fields. In this work, we both study the properties of the resulting warped Gaussian processes as well as using the characterising statistical properties of the warped processes to obtain flexible spatial field reconstructions. In this regard, we derive five different estimators for various important quantities often considered in spatial field reconstruction problems. These include the multi-point Minimum Mean Squared Error (MMSE) estimators; the multiple point Maximum A-Posteriori (MAP) estimators; an efficient class of multiple-point linear estimators based on the Spatial-Best Linear Unbiased (S-BLUE) estimators; and two multi-point threshold exceedance based estimators, namely the Spatial Regional and Level Exceedance estimators. Simulation results and real data examples show the benefits of using the Tukey g-and-h transformation as opposed to standard Gaussian spatial random fields in a real data application for environmental monitoring.

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. It’s elegantly simplicity was an inspired development by Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

The ability to simulate realistically the electronic structure of superconducting materials is important to understand and predict various properties emerging in both the superconducting topological and spintronics realms. We introduce a tight-binding implementation of the Bogoliubov-de Gennes method, parameterized from density functional theory, which we utilize to explore the bulk and thin films of Nb, known to host a significant superconducting gap. The latter is useful for various applications such as the exploration of trivial and topological in-gap states. Here, we focus on the simulations aspects of superconductivity and study the impact of temperature, Cooper-pair coupling and dimensionality on the size of the superconducting order parameter.

This qualitative study explores the pivotal role of trust in supplier relationships from the perspectives of procurement professionals. Through in-depth interviews with diverse industry stakeholders, the research examines the multifaceted nature of trust, its antecedents, dynamics, challenges, and strategic implications within modern supply chain management. Trust is conceptualized as a cornerstone that fosters collaborative exchanges, mitigates risks, and enhances organizational resilience in a competitive global marketplace. Findings highlight key factors influencing trust formation, including effective communication, ethical conduct, relationship history, transparency, and cultural alignment. Challenges such as perceived opportunism, communication breakdowns, and regulatory compliance issues are identified as barriers requiring proactive management strategies. Strategies for building and maintaining trust emphasize proactive engagement, transparent decision-making, performance evaluation, mutual benefit alignment, and effective conflict management. The study further explores the impact of trust on procurement decisions, supplier performance, innovation capabilities, cost efficiencies, and long-term sustainability. Practically, the research underscores the importance of integrating trust-building initiatives into supplier relationship management strategies to optimize operational efficiencies, foster innovation, and achieve sustainable growth. By aligning procurement practices with supplier capabilities and market dynamics, organizations can navigate complexities, seize opportunities, and enhance strategic partnerships that drive mutual value creation. Future research directions include exploring emerging trends such as digitalization, sustainability, and ethical considerations in trust-based supply chain interactions.

This qualitative study investigates the influence of organizational culture on procurement practices across multiple industries, aiming to enrich understanding of how cultural dynamics shape decision-making, supplier relationships, and strategic outcomes within procurement departments. Through semi-structured interviews with procurement professionals, organizational leaders, and industry experts, data were gathered to explore the impact of leadership styles, ethical frameworks, industry dynamics, and external influences on procurement strategies. Findings reveal that transformational leadership fosters innovation, strategic alignment, and long-term partnerships in procurement, whereas transactional and autocratic styles may prioritize cost efficiency over broader strategic goals. Ethical cultures within organizations significantly influence supplier selection criteria and procurement decisions, highlighting the importance of integrating ethical standards consistently to mitigate risks and enhance organizational reputation. Industry-specific dynamics necessitate adaptive procurement strategies tailored to technological advancements, regulatory requirements, and market conditions. Effective supplier relationship management practices, emphasizing trust, transparency, and mutual value creation, enhance procurement effectiveness and resilience. Organizational structures, including centralized, decentralized, and hybrid models, play crucial roles in optimizing procurement operations. Learning cultures promoting continuous improvement and knowledge sharing foster innovation and resilience in procurement practices. External factors such as market volatility, regulatory changes, and geopolitical risks underscore the need for adaptive procurement strategies and robust risk management practices. This study contributes to theoretical insights and practical implications for aligning organizational culture with strategic procurement objectives to optimize effectiveness, mitigate risks, and drive sustainable value creation across supply chains.

Supplier diversity initiatives in procurement have emerged as strategic imperatives for organizations aiming to enhance competitiveness and foster socio-economic equity. This research investigates the impact of supplier diversity initiatives across various industries, analyzing implementation strategies, challenges, and outcomes through a mixed-methods approach. Qualitative data, including interviews with procurement professionals and case studies of exemplary organizations, reveal diverse approaches to implementing supplier diversity—from formalized programs with dedicated resources to ad hoc initiatives driven by regulatory compliance or social responsibility goals. Challenges identified include the identification and qualification of diverse suppliers, scalability issues, and internal resistance within procurement teams. Quantitative analysis of survey data highlights positive impacts on organizational performance metrics, such as procurement spend allocation towards diverse suppliers, supplier-driven innovation, and enhanced supply chain resilience. Best practices in successful supplier diversity programs underscore strategic alignment with overall procurement strategies, effective supplier relationship management, and strong leadership commitment. Socio-economic impacts encompass economic inclusion, community engagement, and skills development among diverse supplier networks, contributing to local economic growth and broader social benefits. Despite these benefits, challenges remain in measuring qualitative outcomes and overcoming systemic barriers to implementation. Cultivating an inclusive organizational culture and leveraging leadership support are crucial for sustaining supplier diversity efforts. Continued collaboration and innovation in supplier diversity practices are recommended to maximize benefits and drive meaningful socio-economic impact globally.

This qualitative study explores supplier selection criteria from the perspectives of procurement professionals across diverse industries. Supplier selection is crucial for organizational efficiency and performance, influenced by factors beyond traditional cost considerations. The research aims to uncover nuanced criteria such as quality assurance, supplier reliability, innovation capability, sustainability practices, strategic alignment, relational dynamics, and risk management strategies. These criteria reflect a shift towards holistic evaluation frameworks that integrate economic, social, and environmental dimensions in procurement decision-making. Methodologically, the study employed semi-structured interviews with 30 procurement professionals, ensuring depth and diversity in perspectives. Thematic analysis was used to identify recurring themes and patterns, illuminating the complexities and strategic importance of supplier selection processes. Findings highlight the strategic role of suppliers in driving innovation, enhancing supply chain resilience, and supporting organizational goals. Moreover, the study underscores the significance of sustainable sourcing practices, ethical considerations, and effective supplier relationships in fostering long-term partnerships and mitigating operational risks. Practical implications suggest that organizations should adopt integrated approaches to supplier selection, leveraging data-driven insights and technological advancements to optimize decision-making. By prioritizing strategic alignment, fostering collaborative partnerships, and implementing robust risk management strategies, organizations can navigate uncertainties, capitalize on market opportunities, and sustain competitive advantage.

This qualitative study explores the intricate impact of cultural differences on global procurement practices within multinational supply chains. Cultural dimensions profoundly influence communication dynamics, negotiation strategies, decision-making processes, and supplier relationship management in diverse global contexts. Effective cross-cultural communication is crucial for fostering trust and clarity across different cultural norms, while negotiation strategies vary based on cultural preferences for collaboration or competition. Decision-making processes are shaped by cultural attitudes towards risk tolerance, time orientation, and decision authority, influencing procurement agility and resilience. Strategic implications of cultural diversity include opportunities for innovation and localized adaptation in procurement practices, tempered by challenges such as adaptation costs and regulatory compliance. Emotional intelligence (EI) emerges as pivotal in navigating cultural complexities, enhancing stakeholder engagement, conflict resolution, and collaborative partnerships critical for sustainable procurement practices in multicultural settings. Economic factors, including stability, currency fluctuations, and market volatility, impact procurement strategies and supply chain resilience, necessitating proactive risk management and adaptive approaches. Barriers to growth in global procurement, such as regulatory complexities and geopolitical risks, require strategic planning, stakeholder collaboration, and infrastructural investments for operational continuity. By understanding and addressing cultural influences, multinational corporations can enhance cross-cultural competence, strategic decision-making, and capitalize on global market opportunities. This study contributes insights and recommendations to enhance procurement effectiveness and competitiveness in an interconnected global economy, supporting ongoing efforts to optimize global procurement practices.

This qualitative research explores the integration of sustainability into procurement practices through the perspectives of supply chain practitioners. The study examines key challenges, strategies, and perceived benefits associated with sustainable procurement across diverse industries. Data were collected via semi-structured interviews with purposively sampled participants renowned for their expertise in procurement and sustainability. Thematic analysis revealed that while regulatory compliance, supplier engagement, and cost considerations pose significant challenges, strategies such as collaborative partnerships, embedding sustainability criteria into procurement contracts, and leveraging technology are pivotal in promoting sustainable procurement. Participants highlighted benefits including enhanced brand reputation, improved operational efficiencies, and strengthened stakeholder trust. Leadership commitment and organizational culture emerged as critical drivers of successful sustainable procurement initiatives, influencing employee engagement and organizational resilience. Looking forward, emerging trends such as circular economy principles and the integration of sustainability into corporate strategies are identified as transformative for future procurement practices. The study underscores the strategic importance of sustainability in enhancing organizational resilience, mitigating risks, and creating long-term economic, environmental, and social value. By addressing challenges, leveraging effective strategies, and embracing emerging trends, organizations can position themselves as leaders in sustainable procurement, contributing positively to global sustainability goals and gaining competitive advantage.

This qualitative study explores the multifaceted strategies organizations employ to build resilient supply chains through effective procurement risk management. Conducted over a six-month period in 2024, the research involved semi-structured interviews with 25 industry professionals from sectors including manufacturing, retail, healthcare, and technology, alongside document analysis and case studies. The study identifies four key themes: risk identification and assessment, supplier relationship management, digitalization in risk management, and strategic resilience practices. The findings reveal that organizations face diverse risks, including supplier, supply market, and external environmental risks, necessitating comprehensive risk assessment methodologies. Supplier relationship management emerges as a critical factor in mitigating risks, with practices such as regular audits, collaborative risk management, long-term partnerships, and supplier diversification being crucial. The adoption of digital technologies like predictive analytics, blockchain, advanced analytics, and artificial intelligence enhances risk management capabilities, providing data-driven insights and fostering transparency. Strategic resilience practices, including inventory buffering, flexible sourcing, redundancy, and scenario planning, are essential for maintaining supply chain continuity amidst disruptions. The study underscores the importance of an integrated and proactive approach to procurement risk management that leverages robust assessment, strong supplier relationships, digital tools, and strategic planning. These findings contribute to a deeper understanding of how organizations can effectively manage procurement risks and build resilient supply chains in a dynamic global environment. The insights offer valuable guidance for procurement professionals and organizational leaders in developing resilient and adaptable supply chain strategies to navigate the complexities of today's market.

Strategic procurement practices within global supply chains are crucial for organizations aiming to navigate complex challenges and achieve sustainable competitive advantage. This qualitative research explores how procurement has evolved from a cost-centric function to a strategic enabler of broader organizational objectives, including risk management, sustainability, and innovation. Through semi-structured interviews with procurement managers and supply chain executives across diverse industries, the study investigates key themes such as supplier relationship management, technological integration, and the impact of sustainability considerations on procurement decision-making. Findings indicate that effective procurement strategies, such as strategic sourcing and collaborative supplier partnerships, are pivotal in enhancing supply chain resilience and operational efficiency. Technological advancements, particularly artificial intelligence and big data analytics, are transforming procurement operations by optimizing processes and enhancing decision-making capabilities. However, the study identifies significant challenges, including regulatory complexities, geopolitical uncertainties, and internal resistance to change, which require adaptive approaches to procurement management. Sustainability emerges as a critical driver, with organizations adopting ethical sourcing practices, reducing carbon footprints, and promoting supplier diversity to meet environmental and social responsibility goals. Leadership qualities such as visionary thinking and emotional intelligence are essential for navigating these challenges and driving innovation within procurement practices. Overall, this research contributes to a deeper understanding of strategic procurement's role in organizational strategy and offers practical insights for enhancing procurement effectiveness and resilience in a competitive global market landscape.

This qualitative research explores the role of digital transformation in procurement through insights gathered from interviews with industry leaders. Digital technologies such as Robotic Process Automation (RPA), Big Data Analytics, Artificial Intelligence (AI), and Blockchain are examined for their impact on operational efficiency, strategic procurement management, supplier relationships, and sustainability practices. Findings reveal that these technologies streamline processes, enhance decision-making capabilities, and improve transparency, thereby enabling organizations to achieve greater agility and competitive advantage. Strategic factors including leadership commitment, strategic investments, and digital skills development emerge as crucial for navigating challenges such as organizational resistance, data security, and integration complexities. The study underscores the transformative potential of digital transformation in procurement, emphasizing its role in driving innovation, fostering sustainability, and aligning procurement practices with broader organizational goals. Looking forward, the research suggests that organizations must continue to innovate and adapt to technological advancements to maintain resilience and leadership in a digital economy. By integrating digital strategies effectively, organizations can enhance operational efficiencies, strengthen supplier relationships, and promote ethical business practices, ultimately positioning themselves for sustained success.

This study investigates how organizations adapt their procurement practices in response to supply chain disruptions, aiming to enhance resilience and ensure operational continuity. Through qualitative research involving interviews with procurement professionals and industry experts, the study identifies key adaptive strategies employed by organizations, including supplier diversification, enhanced inventory management, digital transformation, supplier collaboration, and contingency planning. These strategies are explored in depth, highlighting their implementation challenges and the outcomes achieved. Despite facing obstacles such as financial constraints, technological barriers, and supplier resistance, organizations have demonstrated a proactive approach in leveraging these strategies to mitigate risks and improve supply chain resilience. The findings reveal that adaptive procurement strategies have led to significant outcomes, including strengthened supplier relationships, increased operational efficiency, better risk management, and competitive advantage. These outcomes underscore the strategic importance of agility, technological integration, collaborative partnerships, and effective leadership in responding to disruptions and maintaining competitiveness. The study also discusses implications for practice and policy, emphasizing the need for continued investment in technology, collaboration, and resilience-building initiatives across supply chains. Overall, this research contributes to the understanding of how organizations can adapt and innovate in the face of dynamic supply chain challenges, providing insights that can guide future research and inform strategic decision-making in procurement and supply chain management.

This study investigates the adoption of emerging technologies in procurement within supply chain management, focusing on the transformative potential of artificial intelligence (AI) and blockchain. Through a qualitative approach, involving semi-structured interviews with procurement professionals and technology experts, the study explores how these technologies enhance operational efficiency, optimize inventory management, and improve supply chain transparency and trust. AI-driven predictive analytics were found to significantly enhance demand forecasting, inventory optimization, and supplier performance evaluation, fostering data-driven decision-making and proactive risk management. Blockchain technology ensures secure and transparent transactions, facilitating compliance with ethical sourcing standards and reducing risks associated with counterfeit goods. Despite these benefits, organizations face substantial challenges in adopting these technologies, including data security concerns, integration complexities with existing IT infrastructure, and skills shortages in AI and blockchain expertise. Leadership commitment and organizational readiness are identified as crucial enablers for overcoming these barriers and driving successful technology adoption. The study also highlights the strategic importance of supplier relationship management, emphasizing how emerging technologies enhance real-time collaboration, performance insights, and contractual transparency. By addressing these challenges and leveraging technological innovations strategically, organizations can achieve sustainable growth, resilience, and competitive advantage in an increasingly digital and interconnected global economy. The findings contribute to advancing knowledge on procurement innovation and offer valuable insights for organizations seeking to navigate the complexities of technology-driven procurement practices. Future research directions may explore the long-term impact of technology adoption on supply chain dynamics, sustainability initiatives, and organizational performance.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Foundational and state-of-the-art anomaly detection methods through power system state estimation are reviewed. The traditional components for bad data detection such as chi-square testing, residual-based methods, and hypothesis testing are discussed to explain the motivations for recent anomaly detection methods given the increasing complexity of power grids, energy management systems, and cyber-threats. In particular, state estimation anomaly detection based on data-driven quickest change detection and artificial intelligence are discussed and directions for research are suggested with particular emphasis on considerations of the future smart grid.

In recent years, a range of problems under the broad umbrella of computer vision based analysis of ancient coins have been attracting an increasing amount of attention. Notwithstanding this research effort, the results achieved by the state of the art in published literature remain poor and far from sufficiently well performing for any practical purpose. In the present paper we present a series of contributions which we believe will benefit the interested community. We explain that the approach of visual matching of coins, universally adopted in existing published papers on the topic, is not of practical interest because the number of ancient coin types exceeds by far the number of those types which have been imaged, be it in digital form (e.g., online) or otherwise (traditional film, in print, etc.). Rather, we argue that the focus should be on understanding the semantic content of coins. Hence, we describe a novel approach—to first extract semantic concepts from real-world multimodal input and associate them with their corresponding coin images, and then to train a convolutional neural network to learn the appearance of these concepts. On a real-world data set, we demonstrate highly promising results, correctly identifying a range of visual elements on unseen coins with up to 84% accuracy.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important parameter for diagnostics as well as a promising target for therapeutic interventions in birth defects, injury, and cancer. However, despite much progress in cell and molecular biology, little is known about bioelectric states in human stem cells. Here, we present simple methods to simultaneously track ion dynamics, membrane voltage, cell morphology, and cell activity (pH and ROS), using fluorescent reporter dyes in living human neurons derived from induced neural stem cells (hiNSC). We developed and tested functional protocols for manipulating ion fluxes, membrane potential, and cell activity, and tracking neural responses to wounding and re-innervation in vitro. Finally, using morphology sensor, we tested and quantified the ability of physiological actuators (neurotransmitters and pH) to manipulate nerve wound re-innervation. These methods are not specific to a particular cell type and should be broadly applicable to the study of bioelectrical controls across a wide range of combinations of models and endpoints.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Sorting nexins (SNXs) are a highly conserved membrane-associated protein family that plays a role in regulating protein homeostasis. This family of proteins is unified by their characteristic phox (PX) phosphoinositides binding domain. Along with binding to membranes, this family of SNXs also comprises a diverse array of protein-protein interaction motifs that are required for cellular sorting and protein trafficking. SNXs play a role in maintaining the integrity of the proteome which is essential for regulating multiple fundamental processes such as cell cycle progression, transcription, metabolism, and stress response. To tightly regulate these processes proteins must be expressed and degraded in the correct location and at the correct time. The cell employs several proteolysis mechanisms to ensure that proteins are selectively degraded at the appropriate spatiotemporal conditions. SNXs play a role in ubiquitin-mediated protein homeostasis at multiple levels including cargo localization, recycling, degradation, and function. In this review, we will discuss the role of SNXs in three different protein homeostasis systems: endocytosis lysosomal, the ubiquitin-proteasomal, and the autophagy-lysosomal system. The highly conserved nature of this protein family by beginning with the early research on SNXs and protein trafficking in yeast and lead into their important roles in mammalian systems. Underlying the importance of SNXs in protein homeostasis, genetic defects in SNXs have been linked with a variety of human diseases such as cancer, cardiovascular disease, neurogenerative disease, and viral infections.

The Greenland Ice Sheet is now the largest land ice contributor to global sea level rise, largely driven by increased surface meltwater runoff from the ablation zone, i.e. areas of the ice sheet where annual mass losses exceed gains. This small but critically important area of the ice sheet has expanded in size by ~50% since the early 1960s, and satellite remote sensing is a powerful tool for monitoring the physical processes that influence its surface mass balance. This review synthesizes key remote sensing methods and scientific findings from satellite remote sensing of the Greenland Ice Sheet ablation zone, covering progress in 1) radar altimetry, 2) laser (lidar) altimetry, 3) gravimetry, 4) multispectral optical imagery and, 5) microwave and thermal imagery. Physical characteristics and quantities examined include surface elevation change, gravimetric mass balance, reflectance, albedo, and mapping of surface melt extent and glaciological facies and zones. The review concludes that future progress will benefit most from methods that combine multi-sensor, multi-wavelength, and cross-platform datasets designed to discriminate the widely varying surface processes in the ablation zone. Specific examples include fusing laser altimetry, radar altimetry, and optical stereophotogrammetry to enhance spatial measurement density, cross-validate surface elevation change, and diagnose radar elevation bias; fusing optical imagery, radar imagery, and microwave scatterometry to discriminate between snow, liquid water, refrozen meltwater, and bare ice near the equilibrium line altitude; combining optical reflectance with laser altimetry to map supraglacial lake, stream, and crevasse bathymetry; and monitoring the inland migration of snowlines, surface melt extent, and supraglacial hydrologic features.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

Remote sensing technologies are critical for analyzing the escalating impacts of global climate change and increasing urbanization, providing vital insights into land surface temperature (LST), land use and cover (LULC) changes, and the identification of urban heat island (UHI) and surface urban heat island (SUHI) phenomena. This research focuses on the nexus between LULC alterations and variations in LST and air temperature (Tair), with a specific emphasis on the intensified SUHI effect in Kharkiv, Ukraine. Employing an integrated approach, the study analyzes time-series data from Landsat and MODIS satellites, alongside Tair climate records, utilizing machine learning techniques and linear regression analysis. Key findings indicate a statistically significant upward trend in Tair and LST during summer months from 1984 to 2023, with a notable positive correlation between Tair and LST across both datasets. MODIS data exhibit a stronger correlation R² = 0.879, compared to Landsat R² = 0.663. The application of supervised classification through Random Forest algorithms and vegetation indices on LULC data reveals significant alterations, manifested as a 70.3% increase in urban land, concurrently with a decrement in vegetative cover, especially 15.5% reduction in dense vegetation and a 62.9% decrease in sparse vegetation. Change detection analysis elucidates a 24.6% conversion of sparse vegetation into urban land, underscoring a pronounced trajectory towards urbanization. Temporal and seasonal LST variations across different LULC classes were analyzed using kernel density estimation (KDE) and boxplot analysis. Urban areas and sparse vegetation had the smallest average LST fluctuations, at 2.09°C and 2.16°C, respectively, but recorded the most extreme LST values. Water and dense vegetation classes exhibited slightly larger fluctuations of 2.30°C and 2.24°C, with the bare land class showing the highest fluctuation 2.46°C, but fewer extremes. Quantitative analysis with the application of Kolmogorov-Smirnov tests across various LULC classes substantiated the normality of LST distributions p > 0.05 for both monthly and annual data sets. Conversely, the Shapiro-Wilk test validated the normal distribution hypothesis exclusively for monthly data, indicating deviations from normality in the annual data. Thresholded LST classifies urban and bare lands as warmest classes with 39.51°C, 38.20°C and water by 35.96°C and dense vegetation 35.52°C, sparse vegetation 37.71°C as coldest, a trend consistent annually and monthly. The analysis of SUHI effects demonstrates an increasing trend in UHI intensity, with statistical trends indicating a growth in average SUHI values over time. This comprehensive study underscores the critical role of remote sensing in understanding and addressing the impacts of climate change and urbanization on local and global climates, emphasizing the need for sustainable urban planning and green infrastructure to mitigate UHI effects.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

The elevated or depressed transition temperatures observed in cuprate and pnictide superconductors and other exotic superconductors pose a challenge in the context of explaining them through the traditional Bardeen-Cooper-Schrieffer (BCS) models of superconductivity. A significant obstacle in understanding this phenomenon can be addressed by considering an alternative electron distribution. Our investigation has identified an anyonic distribution, where the occupancy of a site created by removing a hole is filled by an electron. In heavy fermion superconductors (HFSs) block spins must be included in the distribution. The interplay, that is, resonance between superconducting electrons within the conventional BCS framework and independent charge density waves (CDWs) might contribute to driving the high-transition-temperature superconductors (HTSCs).

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

At the Rio Conference in 1992, the sustainable development agenda promised a new era for natural resource management, where the well-being of human society would be enhanced through the sustainable use of natural capital. Several decades on, economic growth continues unabated at the expense of natural capital, as evidenced by biodiversity loss, climate change and further environmental issues. Why is this happening and what can be done about it? In this research, we present three Agent-Based Models that explore the social, economic and governance factors driving (un)sustainability in complex social-ecological systems. Our modelling results reinforce the idea that the current economic system does not protect the natural capital on which it depends. This is due to a disjunction between the economic and environmental elements upon which the sustainable development paradigm is founded. Additionally, various factors appear to enhance social-ecological system unsustainability: the role of financial entities and monetary debt; economic speculation; technological development and efficiency; lack of long-term views and late government interventions; inefficient tipping point management; and the absence of strong top-down and bottom-up conservation forces. Interestingly, alternative scenarios showed that these same factors could be redirected to enhance sustainable development. The current economic system may, therefore, not be inherently unsustainable, but rather specific economic mechanisms, agents’ decision-making, and the kinds of links between economic and natural systems could be at the root of the problem. We argue that short- and medium-term sustainability can be enhanced by implementing mechanisms that shift capitalist forces to support environmental conservation. Long-term sustainability, however, requires further paradigm change: where the economy integrates, and fully accounts for, externalities and recognises the actual value of natural capital.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

Despite the increase of seminary training, Black clergywomen continuously undergo subjugation, degradation, and humiliation in ministry leadership due to gender and race bias (Leslie, 2013) by clergymen. This article reports the findings of a qualitative study that examined the experiences of Black clergywomen regarding obstacles in ministry leadership and how these clergywomen ascribed meaning to their experiences. The two primary research questions were, “What are the experiences of Black clergywomen regarding obstacles in ministry leadership?” and “How do Black clergywomen attribute meaning to their experiences regarding obstacles in ministry leadership?” The results of the study indicated that bias of gender and inequality exists among clergymen; however, the Black clergywomen learned to embrace the experiences and learned from them. The conclusion of this article includes a discussion regarding practical implications of the education of clergy; and the re-evaluation of the perception of Black clergywomen and their experiences. The purpose of this qualitative study was to explore the experiences of Black clergywomen pertaining to challenges in clergy leadership and to explore how Black clergywomen attributed meaning to their experiences regarding challenges in ministry leadership.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Escherichia coli phage Eco_BIFF was isolated from several laboratory stocks of E. coli K-12 MG1655 derivatives. The source of the contamination is unknown. Eco_BIFF is a lytic phage that shows effective growth inhibition of E. coli K-12. Here, we announce the complete genome sequence of Eco_BIFF, and major findings from its genome annotation.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

The pig is an important source of meat production and provides a valuable model for certain human diseases. MicroRNA (miRNA), which is non-coding RNA and regulates gene expression at the posttranscriptional level, plays a critical role in various biological processes. Studies on identification and function of mature miRNAs in multiple pig tissues are increasing, yet the literature is limited. Therefore, we reviewed current research to determine the miRNAs expressed in specific pig tissues that are involved in carcass values (including muscle and adipocytes), reproduction (including pituitary, testis, and ovary), and development of some solid organs (e.g., brain, lung, kidney, and liver). We also discuss the possible regulating mechanisms of miRNA. Finally, as pig organs are suitable candidates for xenotransplantation, biomarkers of their miRNA in xenotransplantation were evaluated.

Subversion of programmed cell death-based host defence systems is a prominent feature of infections by large DNA viruses. African swine fever virus (ASFV) is a large DNA virus and sole member of the Asfarviridae family that harbors the B-cell lymphoma 2 or Bcl-2 homolog A179L. A179L has been shown to bind to a range of cell death inducing host proteins including pro-apoptotic Bcl-2 proteins as well as the autophagy regulator Beclin. Here we report the crystal structure of A179L bound to the Beclin BH3 motif. A179L engages Beclin using the same canonical ligand binding groove that is utilized to bind to pro-apoptotic Bcl-2 proteins. The mode of binding of Beclin to A179L mirrors that of Beclin binding to human Bcl-2 and Bcl-xL as well as murine gamma-herpesvirus 68. Introduction of bulky hydrophobic residues into the A179L ligand binding groove via site directed mutagenesis ablates binding of Beclin to A179L, leading to a loss of ability of A179L to modulate autophagosome formation in Vero cells during starvation. Our findings provide a mechanistic understanding for the potent autophagy inhibitory activity of A179L and serve as a platform for more detailed investigations into the role of autophagy during ASFV infection.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

While referral-level medicine is important in the veterinary curriculum, students also need a solid base knowledge of clinically relevant routine surgery and diagnostic skills. Veterinary hospitals must maintain a steady caseload that provides wellness cases and commonly encountered conditions. Shelter Medicine programs can create the opportunities to meet these challenges. Students can gain quantifiable surgical experience in spay/neuter with measured growth in surgical efficiency and competency while providing needed community service for animal shelters. Students can directly interact with shelter animals by performing examinations, diagnostic testing, and development of treatment protocols and recommendations for commonly encountered problems. Furthermore, students can obtain a working knowledge of biosecurity on a population level to minimize risk of infectious diseases spreading to healthy populations.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

We present a discussion and analysis regarding the benefits and limitations of open and non-anonymized peer review based on literature results and responses to a survey on the reviewing process of alt.chi, a more or less open-review track within the CHI conference, the predominant conference in the field of human-computer interaction (HCI). This track currently is the only implementation of an open-peer-review process in the field of HCI while, with the recent increase in interest in open science practices, open review is now being considered and used in other fields. We collected 30 responses from alt.chi authors and reviewers and found that, while the benefits are quite clear and the system is generally well liked by alt.chi participants, they are reluctant to see it used in other venues. This concurs with a number of recent studies that suggest a divergence between support for a more open review process and its practical implementation. The data and scripts are available on https://osf.io/vuw7h/, and the figures and follow-up work on http://tiny.cc/OpenReviews.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Fertility preservation technologies have existed for decades, and the field is rapidly advancing; limited data exist regarding the use of these technologies by transgender patients. Many options are available for transgender patients who wish to preserve fertility before transitioning. These options include the cryopreservation of gametes, ovarian tissue, or embryos. Currently, ejaculated, or testicular sperm, immature oocytes, and ovarian tissue can be preserved for later use, but no such use option exists for immature testicular tissue. Many financial, sociological, and legal barriers and a lack of awareness among physicians and patients also hindered the utilization of these fertility preservation services. While options are abundant, usage rates are relatively low. The initial data regarding the successful use of preserved tissues appears promising, with birth rates not dissimilar to non-transgender patients. Further investigations into this area are needed. In addition, counseling regarding fertility preservation options should become a significant part of the provider-patient conversation before transitioning therapies.; fertility; transgender; reproductive technology.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

On February 28, 2023, the Facebook page of the United Nations Children's Fund (UNICEF) South Africa, announced the beginning of the HPV vaccination campaign for 2023. The aim of this study was to examine the attitudes of Facebook users, who commented on the UNICEF South Africa post, towards HPV vaccination to inform the development and implementation of interventions that can increase HPV vaccine acceptance and uptake. Several comments were questions regarding the eligible criteria for vaccination, side effects, consent form, and vaccination strategies. Many Facebook users were hesitant towards HPV vaccination due to various reasons including concerns around side effects, religious beliefs, vaccine stock outs, and their distrust in the institutions or systems involved in vaccination programmes. Few users accepted HPV vaccination because they believed that it was very important thing to do, beneficial for the children’s health, and they have vaccinated they children before. Our findings of the current study contribute to the promotion of acceptance and uptake of HPV vaccination by developing and implementing interventions tailored to address identified barriers that are associated with hesitant to HPV vaccination.

This review article seeks to provide relevant information about the applicability of cell-based assays in assessing cytotoxicity of phytochemicals in light of several traditional methods available. Phenolic compounds and other phytochemicals are significant resources for drug discovery and development, thus underlining the enormous potentials of plant-derived natural products for the prevention and management of oxidative stress associated with cancer and other diseases. These effects have been linked to the content of phytochemicals such as phenolic compounds and their antioxidant properties. The abundance and complexity of these bio-constituents highlight the need for well-defined methods for the in vitro characterization and quantification of extracts and/or preparations that can translate to in vivo effects. Cell culture systems provide a useful model for basic research and a wide range of clinical in vitro studies and physiological processes as well as assessing the toxicity and therapeutic potential of compounds including plant extracts with potential medicinal benefits. Their use in cancer research provide a useful insight into possible therapeutic properties of phytochemicals at the cellular level. This approach has been instrumental in the initial stages of developing chemotherapeutic agents where human cancer cell lines are used as experimental models. These models have continued to contribute to elucidating specific requirements for certain biochemical events associated with proliferation, metabolism, loss of cell viability/apoptosis. Cell culture systems remain a promising tool in natural product development.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Understanding the strength of the associations between perceived risk and individuals’ behavioral intentions to protect their health is important for determining appropriate risk communication strategies in communities impacted by lead contamination. We conducted a survey within communities of northern Idaho, USA (n = 306) near a Superfund megasite with legacy mining contamination. We empirically test a theoretical model based on the Health Belief Model. Survey respondents had higher intentions to practice health protective behaviors when they perceived the risk of lead contamination as severe, recognized the benefits of health protective behaviors, and considered the risks of lead contamination. Women reported higher behavioral intentions than men, but age and mining affiliation did not have an association. Survey comments indicated that perceptions about the long-term environmental remediation in the region influenced risk perceptions. Understanding risk perceptions, behavioral intentions, and related factors can aid public health agencies in tailoring risk communication for increasing protective behaviors in mining-impacted communities internationally.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

We investigated 328 SARS-CoV-2 cases in Barwon South West Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data from three sequential questionnaires on case characteristics and symptom progression were examined. Multivariable logistic regression were used to model associations between demographic profile and symptoms. Asymptomatic cases were more than three times as likely to be from ethnic minority groups [OR 3.2, 95% CI 1.5 – 6.7, p&lt;0.01], and approximately seven times more likely to be seniors (≥ 65 years) [OR 7.3, 95% CI 1.0 – 50.1] after adjusting for sex and occupation. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross protection from other coronaviruses in the early stages of the COVID-19 pandemic. This research should be repeated post-vaccination to reassess symptom expression according to ethnicity, and better comprehend case ascertainment impacts of cultural biases in testing and infection reporting, and the reliance on symptoms to trigger testing. These findings may in part reflect differences in testing patterns by ethnicity and true differences in disease expression, both important for appropriate transmission prevention strategies, and tailoring testing messaging towards ethnic minority communities.

The article explores the concept of 'synthetic man' (SM) in the context of 'synthetic biology' (SB), analysing the potential, challenges, and ethical implications of these achievements. Through dialogue with ChatGPT 4, an in-depth understanding of the evolution, contributions of SM, ChatGPT's contribution, and concerns associated with SM is sought, providing insight into how this technology could affect our society. Our study uses a structured dialogue framework with ChatGPT that addresses essential SM questions regarding SM history, contributions, challenges, and concerns. ChatGPT responses are analysed to extract relevant information and identify trends and insights. The ChatGPT dialogue reveals that MS is still a theoretical and speculative concept with significant advances in gene therapy and genetic engineering. The potential contributions of SM in addressing global challenges such as health, environment and education are identified. Ethical and social concerns such as health risks and psychological impact are also highlighted. Differences in ChatGPT responses were observed between different sessions or even within the same session, which highlighted the limitations in the replicability of the research and sometimes the need for clarification of the questions. The article is distinguished by its unique approach of using an advanced language model to explore a complex and speculative topic. The LLM Dialogue Framework on Technology (LLM-DFonTech) framework proposal for structured dialogue with ChatGPT on various technological topics related to the original contribution provides an adaptable tool for interdisciplinary research in emerging technologies. This methodology opens up new possibilities for analyzing and developing trends in technology and society.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Communication is a key method of expressing one's thoughts and opinions. Amongst many modalities, speech and writing are the most powerful and common forms of human communication. Analysing what and how people think has inherently been an interesting and progressive research domain. This includes bimodal sentiment analysis which is an emerging area in natural language processing (NLP) and has received a great deal of attention in recent years in a variety of areas including social opinion mining, health care, banking, and so on. At present, there are limited studies on bimodal conversational sentiment analysis as it proves to be a challenging area given the complex nature of the way humans express sentiment cues across various modalities. To address this gap, a comparison of the performance of multiple data modality models has been conducted on the MELD dataset, a widely-used dataset for benchmarking sentiment analysis within the research community. Our work then demonstrates the results of combining acoustic and linguistic representations. Lastly, our proposed neural network-based ensemble learning technique is employed over six transformer and deep learning-based models, achieving a State-Of-The-Art (SOTA) accuracy.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

The recent growth of high-resolution spatial data, especially in developing urban environments, is enabling new approaches to civic activism, urban planning and the provision of services necessary for sustainable development. A special area of great potential and urgent need deals with urban expansion through informal settlements (slums). These neighborhoods are too often characterized by a lack of connections, both physical and socioeconomic, with detrimental effects to residents and their cities. Here, we show how a scalable computational approach based on the topological properties of digital maps can identify local infrastructural deficits and propose context-appropriate minimal solutions. We analyze 1 terabyte of OpenStreetMap (OSM) crowdsourced data to create worldwide indices of street block accessibility and local cadastral maps and propose infrastructure extensions with a focus on 120 Low and Middle Income Countries (LMIC) in the Global South. We illustrate how the lack of physical accessibility can be identified in detail, how the complexity and costs of solutions can be assessed and how detailed spatial proposals are generated. We discuss how these diagnostics and solutions provide a multiscalar set of new capabilities – from individual neighborhoods to global regions – that can coordinate local community knowledge with political agency, technical capability, and further research.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

In 2023, the Bureau of Land Management (BLM) estimated that there were 68,928 mustangs living on United States public lands in 10 western states. The agency uses Appropriate Management Levels to determine the number of mustangs who need to be removed from the land. Once removed and processed, mustangs are sent to adoptions or sales events or retained in short-or long-term holding facilities. Adoptions and sales are the leading avenues for rehoming mustangs; however, the number of horses the BLM can place fluctuates annually and never approaches the greater number removed from the range. To explore opportunities for increasing the number of mustang adoptions, we conducted in-depth interviews with 23 horse trainers located on the U.S. East Coast, asking about participants’ training programs, relationships with horses, perceptions of mustangs, and challenges that mustangs face in the dressage and eventing industries. Participants had varying experiences with mustangs; however, all were willing to work with a mustang in some capacity. Participants voiced the need for more satellite adoption locations on the East Coast to decrease barriers to acquiring a mustang, notably cost and time, and for expanding existing training programs to include eventing and dressage.

The COVID-19 pandemic of 2020 changed the way we interact and engage in commerce at a fundamental level. Social distancing and stay-at-home orders leave businesses and cities wondering what economic activity will look like in the future. Given a likely reduction in face-to-face interactions, it is important to better understand how social interactivity influences economic outcomes. Here we measure the effect of social interactions in the workforce on patent production and economic efficiency. We decompose U.S. occupations into individual work activities, determine which of those activities are associated with face-to-face interactions, and reaggregate the labor force of each U.S. metropolitan statistical area (MSA) into a metric of social interactiveness. We then calculate each MSA’s density of social work activities and find that this measure is more highly correlated with an MSA’s per capita patent production than simple population density. This suggests that density of face-to-face interactions is the important driver of a city’s rate of invention. We close by exploring analogies between the development of cities and the development of stars, suggesting ways these analogies may help frame future research on cities.