The nonlinear dynamics exhibited by aircraft flying at high angle of attack (AOA) pose great challenges to the design of flight control. The control design based on nonlinear dynamic inversion (NDI) is to reversely find the required control input based on the current nonlinear dynamics of the aircraft and the control objectives to be achieved. Since it is derived from the nonlinear dynamics of the aircraft, a single NDI controller can cover the entire flight envelope without the need for controller switching or gain scheduling. This paper employs the layered structure of the flight control loop to implement the NDI controller through the combination of aerodynamic control and thrust vectoring control (TVC). The resulting NDI controller is applied to an experimental F-16 installed with TVC to verify its high AOA maneuverability in the post-stall region. The verification simulation shows that the experimental F-16 under the NDI control can effectively track the high AOA command and successfully demonstrate the Herbst maneuver by performing the heading reversal with 70° AOA.

The surface thermodynamic properties of polymers and copolymers modified by supramolecular structures are very used in several industrial processes, such as selective adsorption, paints, coatings, colloids, and adhesion applications. Background: Inverse gas chromatography at infinite dilution was proved to be the best technique to determine the surface properties of solid surfaces by studying the adsorption of some model polar and non-polar organic molecules adsorbed on solid surfaces by varying the temperature. Methods: The retention volume of adsorbed solvents is a precious parameter to obtain the London dispersive and polar free energies and the London dispersive surface energy of styrene–divinylbenzene copolymer modified by supramolecular structure of melamine using the Hamieh thermal model and our new methodology consisting in the separation of the two polar and dispersive free energy of interaction. This led to the determination of the polar acid and base surface energy, and the Lewis’s acid-base constants of the various solid materials. Results: all surface energetic properties of styrene–divinylbenzene copolymer modified by melamine at different percentages were determined as a function of temperature, following our new methodology. Conclusions: It was observed that the styrene–divinylbenzene copolymer exhibited the highest London dispersive surface energy which decreased when the melamine percentage increased. All materials presented higher Lewis’s basicity and this Lewis’s basicity increased with the percentage of melamine.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

This narrative review examines the crucial role of physical activity in managing long COVID, characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 focusing on long-term COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like CERT, and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity programs in standard care for long COVID to improve patient outcomes and quality of life.

While digitization can make the health industry faster and more efficient, there are many financial, social and organizational obstacles and barriers to its implementation. This article offers a systematic review of the main troubles detected from the literature review. Also there is a proposal of new kind of restrictions to pay attention. Finally, its offer an heterodox reading about the problem analyzed.

Few prior works study self-driving cars by deep learning with IoT collaboration. SDC-Net, which is an end-to-end multitask self-driving car camera cocoon IoT-based system, is one of the research that tackles this direction. However, by design SDC-Net is not able to identify the accident locations, it only classifies if it is a crash scene or not. In this work, we introduce an enhanced design for the SDC-Net system by 1) replacing the classification network with a detection one, 2) adapting our benchmark dataset labels built on the CARLA simulator to include the vehicles bounding boxes while keeping the same training, validation, and testing samples, 3) modifying the shared information via IoT to include the accident location. We keep the same path planning and automatic emergency braking network, the digital automation platform, and the input representations to formulate the comparative study. SDC-Net++ system is proposed to 1) output the relevant control actions, especially in case of accidents: accelerate, decelerate, maneuver, and brake, and 2) share the most critical information to the connected vehicles via IoT, especially the accident locations. A comparative study is also conducted between SDC-Net and SDC-Net++ with the same input representations: front camera only, panorama and bird-eye views, and with single-task networks: crash avoidance only, and multitask networks. Multitask network with a BEV input representation outperforms the nearest representation in precision, recall, f1-score, and accuracy by more than 15.134%, 12.046%, 13.593%, and 5%, respectively. SDC-Net++ multitask network with BEV outperforms SDC-Net multitask with BEV in precision, recall, f1-score, accuracy, and average MSE by more than 2.201%, 2.8%, 2.505%, 2%, and 18.677% respectively.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

The tumor necrosis factor receptor associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-B activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1 secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we show that intraarticular injection of TRAF1 deficient macrophages into knee joints of wildtype (WT) mice subjected to the collagen antibody induced arthritis (CAIA) model of RA significantly exacerbated joint inflammation, immune cell infiltration and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

In the present work, a predictive modelling and optimization with the adaptive network based fuzzy inference system(ANFIS) modelling of mechanical properties of laser-coated NB/SiC/Ni welds was studied based on Taguchi design by laser cladding. An ANFIS model based on a Sugeno type fuzzy inference system was developed for predicting the hardness properties of SiC/BN/Ni welds by laser cladding with experimental data required for network training and prediction. Based on analysis of variance, three important factors were taken as inputs for the fuzzy logic inferences, while the hardness properties was taken as the output of the ANFIS. The microstructure of welds were analysed using scanning electron microscopy with an energy dispersive X-Ray spectrometer. Highly developed leaf-like dendrites and eutectic crystals were found in some areas of the melting zone for the BN/SiC/Ni weld, which was significantly hardened. The ANFIS model based on Taguchi's design provides a better pattern of response because the predicted and experimental values were highly similar. As a result, a satisfactory result was achieved between the predicted and experimental values of hardness in laser-coated NB/SiC/Ni welds, whereby the success and validity of the method was verified.

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.

Personal protective equipment (P PE) rules must be respected and followed to the letter of healthcare professionals in Cameroon to avoid the transmission of infectious diseases. This research proposes solutions to the problems of non-adherence and non-compliance among healthcare workers in Cameroon towards PPE rules. Inadequate access to suitable PPE, discomfort when wearing PPE during poor quality, and a lack of training on correct PPE use are just a few of these obstacles amongst HCWs in Cameroon. Hospitals and healthcare facilities should prioritize offering thorough instruction on PPE use and pinpoint the need to adhere consistently to PPE rules to remove these obstacles. They should also ensure that all healthcare personnel have access to and a sufficient supply of the proper PPE. Through the organization of impromptu visits by surveillance teams to identify areas of support and training, there is a need for assistance from government bodies and public health groups in creating awareness of the security value of PPE use among healthcare professionals. There is a lack of PPE in health care settings in rural areas in Cameroon, thus a need for an adequate supply. Then can we put appropriate PPE policies and practices for HCWs in Cameroon, as they will keep to it.Healthcare professionals in Cameroon must comprehend that following PPE standards protects not just their selves from diseases but also their patients, coworkers, and communities. We are accountable for ensuring everyone's safety and well-being, and adhering to PPE regulations is an essential first step.

This paper undertakes a comprehensive review to underscore the central role of sustainability in the evaluation and innovation of jet grouting technologies. It meticulously traces the evolution of evaluation methodologies, emphasizing the imperative of sustainable practices throughout history. Traditional evaluation paradigms are examined alongside contemporary trends, with a particular focus on sustainability metrics and visualization techniques. Through an examination of innovative jet grouting technologies, this paper illustrates how sustainability principles have driven advancements aimed at improving the efficiency and environmental impact of jet grouting methods. Central to this review is an assessment of sustainability across multiple dimensions, including method applicability, installation and operational compatibility, and the performance of the resulting jet grouted piles. By emphasizing sustainability considerations, the paper highlights the intrinsic link between environmental integrity and technological innovation in the field of jet grouting. In addition, it discusses analytical evaluation methods designed to proactively address sustainability concerns prior to construction, thereby promoting a more environmentally responsible approach. Finally, this paper presents a pioneering evaluation framework that integrates real-time monitoring and visualization tools, allowing stakeholders to track sustainability milestones throughout the construction process. By emphasizing sustainability as a guiding principle, this review advocates for a paradigm shift toward more ecologically sound and resilient jet grouting practices.

The vast array of interconnected microbes across earth’s ecosystems and within holobionts has been called the “Internet of Microbes.” Research into the fundamental microbial properties has demonstrated that bacteria and archaea are masters of energy and information collection, storage, transformation, and dissemination using both “wired” and wireless (at a distance) capacities. These features suggest that microbes are quantum entangled within and between earth’s holobionts, and that specific tools affecting energy and information functions could provide an effective strategy for managing microbial populations. Microbes use four critically important microbial networking functions (sound, light, electricity, and magnetism). This narrative review focuses on microbial management based on two of the four: sound and light (as well as related vibrations). These are examined as: 1) tools for managing microbial populations, 2) tools to support new technologies, and 3) tools for healing humans and other holobionts. Given microbial sensitivity to sound, light, and vibrations, it is critical that microbial populations and microbe-laden holobionts are protected from potentially damaging exposures. We conclude that sound, light, and vibrations are useful therapeutic tools that can help support useful microbial populations and help to address ongoing challenges of holobiont disease.

Being forced to live in an area following a catastrophic landslide may adversely impact people's mental well-being. Unprivileged communities such as Adivasis, Dalits, plantation workers, and people with low incomes in Kerala's hilly districts are forced to live in landslide-affected areas despite their fear. This paper examines the fears and concerns of landslide survivors from the marginalized sections of society from a broader framework of the political economy of mental health. This approach aligns with the assertion made by the World Health Organisation that individual factors do not solely determine mental health but are intricately linked to broader social, political, and economic circumstances. Data were collected through in-depth interviews with fatal landslide survivors and key informants [ ]. The study employed thematic data analysis from in-depth interviews of various fatal landslide survivors since 2018. The three major themes unveiled in the analysis are: 1. post-disaster fears, 2. The factors that triggered fear and concern and 3. Socio-economic marginality and mental health. The study asserts that individuals who are poor and unprivileged are highly susceptible to mental health issues associated with landslides.

This research investigates the complex transformation of the Baltic Clean and Dirty Tankers markets from 1998 to 2023. Our study quantifies the market multifractality in two distinct periods, from 1998 to 2010 and 2010 to 2023. We compare multifractal measures of the original, surrogated, and shuffled data, which indicate high multifractality and a complex market structure influenced by temporal organization and inherent volatility. Shuffled data analysis emphasizes the critical role of temporal sequences within market behaviour. Additionally, the study delves into external factors such as regulatory changes, economic disturbances, technological innovation, and environmental concerns contributing to market complexity. A distinct shift in multifractal values between the two periods suggests an evolution from crisis-induced complexities to a market influenced by diversified and modern dynamics. Our findings offer a concise understanding of the multifractal nature of the tanker markets and how global crises can impact the markets, emphasizing the importance of considering systemic risks in freight market analysis.

This study delves into the intricate interplay of economic growth components, specifically focusing on Consumption and investment in Saudi Arabia from 2000 to 2022. Employing vector error correction models and cointegration techniques, we analyze the short- and long-term dynamics within the relationship of Consumption, investment, and economic growth. Granger causality analysis is also used to discern these pivotal variables' causal connections. Our empirical analysis reveals a persistent long-term cointegration relationship among the variables, underscoring the enduring nature of their interdependency. Furthermore, our findings highlight Consumption and investment's statistically significant positive impact on economic growth. Notably, the short-term analysis unveils a stable model characterized by an annual adjustment to equilibrium of 100%.Moreover, the Granger causality study demonstrates unidirectional causal linkages between Consumption, investment, and economic growth. These findings hold substantial implications for policy formulation in Saudi Arabia. Policymakers must grasp the ramifications of burgeoning prosperity and evolving private consumption patterns on future environmental outcomes. Achieving sustainable long-term results necessitates equal emphasis on bolstering private Consumption and fostering other facets of economic growth.

In this work, an innovative numerical approach for polylinear approximation (polylinearization) of non-self-intersecting compact sensor characteristics (transfer functions) specified either pointwise or analytically is introduced. The goal is to optimally partition the sensor characteristic, i.e. to select the vertices of the approximating polyline (approximant) along with their positions on, the sensor characteristics so that the distance (i.e. the separation) between the approximant and the characteristic is rendered below a certain problem-specific tolerance. To achieve this goal, two alternative non-linear optimization problems are solved, whose essential difference is in the adopted quantitative measure of the separation between the transfer function and the approximant. In the first problem, which relates to absolutely integrable sensor characteristics (their energy is not necessarily finite, but they can be represented in terms of convergent Fourier series), the polylinearization is constructed by numerical minimization of the L^1--metric (a distance-based separation measure), concerning the number of polyline vertices and their locations. In the second problem which covers the quadratically integrable sensor characteristics (whose energy is finite, but they do not necessarily admit a representation in terms of convergent Fourier series), the polylinearization is constructed by minimizing numerically the L^2-metric (area-, or energy-based separation measure) for the same set of optimization variables –the locations, and the number of polyline vertices.

The hyper-arid environment is characterized by high inter-annual climatic fluctuations. The yearly average rainfall can change substantially for several years, forming wet or dry sub-periods. Observing rainfall trends over a sub-period can lead to a false perception of a change in the trend but may in fact represent a periodic cycle when examined on a larger time scale. We aimed to better characterize the rainfall regime prevailing in the hyper-arid Arava Valley (Israel/Jordan), and to examine the response of vegetation to annual rainfall. We hypothesized that annual and perennial vegetation would respond differently to wet and dry sub-periods, and that grazing activities will impact vegetation growth. We used a time series of monthly rainfall, from which we calculated Standard Precipitation Index (SPI), and calculated proxies of perennial and annual vegetation over the last four decades using Landsat-derived Normalized Difference Vegetation Index (NDVI). We found no clear trend in rainfall amounts during this period, however we did identify wet and dry sub-periods which were statistically distinct in rain and in vegetation patterns from each other. The highest levels of correlation between rainfall and the NDVI derived proxies were found when examining average rainfall over a period of two- three years for the annual vegetation and over four years for perennial vegetation. Using the Mann-Kendall test, we identified a time lag of two to four years, with the proxies of annual vegetation responding faster than the proxies of perennial vegetation, to shifts between wet and dry sub-period. In addition, we found a consistent difference between natural vegetation cover in Jordan (grazed) and Israel (non-grazed), favoring the development of natural vegetation on the Israeli side. We conclude that integrating between long-term remote sensing satellite imagery and climatic records revealed the greater resilience of perennial vegetation in the hyper-arid region to climatic fluctuation, and enabled us to identify the vegetation’s sensitivity to anthropogenic impact.

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versa-tile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for under-standing the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other, non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer’s, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal com-plexes have potential applications as radiopharmaceuticals. The examination of these complexes was done by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood. The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments. HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dl), triglycerides (45.45 ± 0.39 mg/dl), LDL-c (66.12 ± 0.10 mg/dl), VLDL-c (19.34 ± 0.16 mg/dl), and a decrease in HDL-c (10.34 ± 0.18 mg/dl). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dl), triglycerides (32.33 ± 0.16 mg/dl), LDL-c (50.34 ± 0.15 mg/dl) and VLDL-c (13.15 ± 0.45 mg/dl) respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dl). 15-oxo ursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol). It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats which might lead to new medication with significant hypolipidemic potential.

Since the creation of the first parallel electrical power systems around the world, the rotor angle stability of synchronously operating generators has been one of the most crucial and challenging problems. In modern electricity networks, involving Kazakhstani, where the renewable energy technologies are rapidly penetrating, and the issue of stability takes on even greater importance due to the technical shortcomings of inverter-based generation. In this framework, an analysis of rotor angle transient stability was carried out when replacing existing synchronous generators with doubly fed induction generators under a certain pre-emergency mode. A critical proportion of active power generation by DFIG units was identified at which transient stability can still be maintained due to the sufficient stored kinetic energy of the synchronous machines remaining in operation. In addition, 2 simple solutions were investigated to improve transient stability, such as an increased time of the automatic reclosure operation and the use of special load shedding automation. For the analysis, a real power system of Mangystau region in Kazakhstan was considered, and the PowerWorld software was used.

Water networks are critical infrastructure components, ensuring the continuous supply of high-quality drinking water to consumers. To secure such water supply, regular maintenance, including the replacement of deteriorating pipelines, is essential. In this study, a methodology has been developed for determining optimal pipeline replacement solutions in water supply systems at water utilities with limited data availability. Hydraulic analysis has been conducted on the segment of 25 km of the water supply network using the free software EPANET. Applying water network optimization, eight pipeline replacement projects according to 13 pre-defined criteria have been identified and evaluated. The paper outlines the methods for evaluating the criteria, including defining specific quantitative limits. The Analytical Hierarchical Process (AHP) method was used in the paper to determine the weights of the criteria. The reason for applying this method refers to problems that involve a set of criteria with a mixed structure, including both quantitative and qualitative aspects. Also, the paper describes the steps of the multi-criteria optimization method VIKOR, used to select the optimal project. This paper, considered as case studie, describes a method, i.e. application of a new principles and an innovative way to solve a problem for developing countries.

A problem of efficacy of crystal growth methods for crystallization from solution or melt has been investigated. Axial vibrational control (AVC) technique was considered as a perspective method to manage both heat-mass transfer and chemical component composition of the melts in the case of crystallization of complex chemical compounds. Numerical modeling and the search for generalized dependencies made it possible to predict the AVC parameters that provide optimal heat and mass transfer modes for creating flat liquid-solid interfaces, as well as the component composition of dissociated melts of various chemical compounds – Ge, NaNO3, CdTe.

Solid tumors universally possess the ability to evade contact inhibition of proliferation (CIP), a mechanism halting cell proliferation when cell-cell contacts occur. Merlin, an ERM-like protein, crucially regulates CIP and is frequently deactivated in various cancers, indicating its signifi-cance as a tumor suppressor in cancer biology. Despite extensive investigations into Merlin's role in cancer, its lack of intrinsic catalytic activity and frequent conformation changes has made it notoriously challenging to study. To address this challenge, we harnessed innovative luciferase technologies to create and validate a split-luciferase biosensor system. This system enables precise quantification of Merlin's conformation and activity both in vitro and within living cells. This biosensor significantly enhances the study of Merlin's molecular functions, serving as a potent tool to explore its contributions to CIP and tumorigenesis.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p<0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p < 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p<0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

The implementation of management systems has become a strategic advantage in achieving business goals, especially in industrial organizations, but the implementation of social responsibility requirements is especially ethical. Large multinational companies have long been developing and, in particular, implementing their own codes of conduct, which include their suppliers, to demonstrate their commitment to Corporate Social Responsibility (CSR). The compliance with CSR requirements from stakeholders is thus extended or intertwined with requirements in established management systems (MSs). The objectives of the study were to (1) analyze the different approaches to CSR in internationally recognized cross-industry and industry-specific standards and codes in different industries; (2) select the most appropriate framework for assessing the degree of applicability of CSR in the selected management systems and develop a methodology for its assessment; (3) apply the proposed methodology (referred to as SRIMS) in the selected areas: automotive industry, research organization, and metallurgical industry; (4) through ANOVA, validate its use for assessing the overall level of CSR applicability in an organization's established management systems. The application of the Bonferroni method confirmed the hypotheses that the developed SRIMS model is a sufficiently appropriate tool for assessing the overall level of applicability of CSR requirements to established MSs.

The increased adoption of information and communication technology for smart grid applications will require innovative cyber-physical system (CPS) testbeds to support research and education in the field. The groundbreaking CPS testbeds with realistic and scalable platforms have progressively gained interest in recent years, with electric power flowing in the physical layer and information flowing in the network layer. However, CPSs are critical infrastructures and not designed for testing or direct training, as any misbehaving in an actual system operation could cause a catastrophic impact on its operation. Based on that, it is not easy to efficiently train professionals in CPSs. Aiming to support the advancement and encourage the training of industry professionals, this paper proposes and develops a complete testbed with commercial tools. The testbed can reliably replicate the performance of smart grid systems and the main potential cyber threats that electric grids may face. The complex interdependencies between the cyber and physical domains are discussed in detail, and different case scenarios are presented, providing insightful guidelines for key features and design decisions for future smart grid testbeds.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

Functional connectivity (FC) is a potential candidate that can increase the performance of brain-computer interfaces (BCIs) in the elderly because of its compensatory role in neural circuits. However, it is difficult to decode FC by current machine learning techniques because of a lack of its physiological understanding. To investigate the suitability of FC in BCI for the elderly, we propose the decoding of lower- and higher-order FCs using a convolutional neural network (CNN) in six cognitive-motor tasks. The layer-wise relevance propagation (LRP) method describes how age-related changes in FCs impact BCI applications for the elderly compared to younger adults. Seventeen younger (24.5±2.7 years) and twelve older (72.5±3.2 years) adults were recruited to perform tasks related to hand-force control with or without mental calculation. CNN yielded a six-class classification accuracy of 75.3% in the elderly, exceeding the 70.7% accuracy for the younger adults. In the elderly, the proposed method increases the classification accuracy by 88.3% compared to the filter-bank common spatial pattern (FBCSP). LRP results revealed that both lower- and higher-order FCs were dominantly overactivated in the prefrontal lobe depending on task type. These findings suggest a promising application of multi-order FC with deep learning on BCI systems for the elderly.

The objective of the present work was to determine the productivity and costs of timber harvesting and skidding during the first commercial thinning of a Scots pine stand. The analyzed harvesting set consisted of a mini-excavator (34 kW) with an stroke harvester head (gripping range: 4–30 cm), and a farm tractor coupled to an logging trailer with a hydraulic crane. Merchantable timber (roundwood with a minimum diameter of 5 cm inside bark) was harvested from a 25-year old planted Scots pine stand growing on a grid of 1.4×1.8 m. The study showed the productivity of the mini-harvester range from 3.09 to 3.47 m3∙PMH15 -1, and that of the forwarding set to be 4.07 m3∙PMH15 -1. The analyzed model of productivity as a function of individual tree volume and thinning intensity was statistically significant, but the intensity parameter was significant only on plots located along wide access trails (3.7 m) and insignificant on plots located along the narrow access trial (2.5m). The intertree distance was not found to be significant. The calculated net machine costs for the forwarding set and mini-harvester were 36.12 Euro∙PMH 1 and 52.47 Euro∙PMH-1, respectively. An increase in the utilization rate of the harvesting set to 80% would reduce the timber harvesting and skidding costs to 22.07 Euro∙m-3.

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

Lomami National Park, located in the Democratic Republic of Congo, is renowned for the integrity of its forest ecosystems, safeguarded by the absence of agricultural activities and limited road access. However, these ecosystems remain under-researched, particularly regarding forest cover dynamics. This research gap poses a significant challenge to establishing rigorous monitoring, which is essential for ensuring the long-term preservation of these valuable ecosystems. This study evaluates land cover dynamics within Lomami National Park through supervised classification of Landsat images from 2008, 2016, and 2024. Seven spatial structure indices were calculated to highlight the dynamics of landscape composition and configuration, distinguishing between the park's core and buffer zones. The underlying spatial transformation processes were identified using a decision tree approach. The results highlight a striking contrast in forest cover stability between Lomami National Park and its surrounding periphery. Within the park, forest cover has not only been preserved but has also shown a modest increase, rising from 92.60% to 92.75%. In contrast, the peripheral zone experienced a significant decline in forest cover, decreasing from 79.32% to 70.48% over the same period. This stability within the park goes beyond simply maintaining forested areas; it includes the preservation and strengthening of the spatial structure of forest ecosystems. For instance, edge density, which is a key indicator of forest edge compactness, remained stable in the park, fluctuating between 8 m/ha and 9 m/ha. However, in the peripheral zone, edge density exceeded 35 m/ha, suggesting that forest edges in the park are considerably more cohesive and intact than in the surrounding areas. Furthermore, the spatial transformation processes within each area underscore these contrasting dynamics. In the park, the main process was aggregation of primary forest patches, which reflects a trend toward continuous and connected forest landscapes. By contrast, the peripheral zone experienced dissection, indicating fragmentation and breakdown of forest patches. Together, these findings underscore the park's role in maintaining both the extent and the structural integrity of forest ecosystems, setting it apart from the more degraded periphery. These findings highlight not only the resilience of forest ecosystems in the face of limited anthropogenic pressures but also the crucial importance of effective land management and rigorous conservation strategies in addressing the challenges of urbanization and surrounding rural expansion. They further emphasize that well-adapted conservation measures, combined with specific demographic and socio-economic conditions, can play a pivotal role in long-term forest preservation and ecological stability.

New asphalt mixtures have been improved by using fibers (polypropylene, polyester, asbestos, carbon, glass, nylon, lignin, coconut, sisal, recycled rubber, PET, wood, bamboo and cellulose), reducing the temperature and compaction energy for their collocation, minimizing the impact on the environment, increasing the tenacity and resistance to cracking of hot mix asphalt (HMA), preventing asphalt drainage in a Stone Mastic Asphalt (SMA). Hence, this paper aims to evaluate the influence of the chemical (lignin content, ash, viscosity, degree of polymerization and elemental analysis), morphological (SEM), spectroscopic (FTIR-ATR and XRD) and calorimetric (ATG and DSC) properties of celluloses from bagasse Agave tequilana Weber var. Azul (ABP), corrugated paperboard (CPB) and commercial cellulose fiber (CC) as Schellenberg drainage (D) inhibitors of the SMA. The ABP was obtained through a chemical process by alkaline cooking, while CPB by a mechanical refining process. The chemical, morphological, spectroscopic and calorimetric properties were similar among the analyzed celluloses, but CPB and ABP cellulose are excellent alternatives to CC cellulose for inhibiting drainage. However, CPB is the most effective at low concentrations. This is attributed to its morphology, which includes roughness, waviness, filament length, orientation and diameter, as well as its lignin content and crystallinity.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of art of BIA utilization by analysing the clinical benefits, limitations, and the potential future developments in this clinically unexplored field.

Background: Heracleum sphondylium, a medicinal plant used in Romanian ethnopharmacology, proved to have a remarkable biological activity. The escalating concerns surrounding antimicrobial resistance led to a special attention to new efficient antimicrobial agents based on medicinal plants and nanotechnology. We report the preparation of a novel, simple phytocarrier that harnesses the bioactive properties of H. sphondylium and silver nanoparticles (HS-Ag system). Methods: The H. sphondylium low-metabolic profile was determined through gas chromatography–mass spectrometry and electrospray ionization–quadrupole time-of-flight–mass spectrometry. The morphostructural properties of the innovative phytocarrier were analyzed by X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The antioxidant activity was evaluated using total phenolic content, ferric reducing antioxidant power, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro assays. The antimicrobial activity screening against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli was conducted using the agar well diffusion method. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay estimated the in vitro potential cytotoxicity on normal human dermal fibroblasts (NHDF) and cervical cancer (HeLa) cells. Results: A total of 88 biomolecules were detected, such as terpenoids, flavonoids, phenolic acids, coumarins, phenylpropanoids, iridoids, amino acids, phytosterols, fatty acids. HS-Ag phytocarrier heightened efficacy in suppressing the growth of all tested bacterial strains compared to H. sphondylium and exhibited a significant inhibition of HeLa cell viability. Conclusions: The new HS-Ag phytocarrier system holds promise for a wide range of medical applications. The data confirms the capacity to augment pertinent theoretical understanding in the innovative field of antimicrobial agents.

In the global fight against malaria, standard vector control methods such as indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are intended to protect inside residential structures and sleeping spaces. However, these methods can still leave individuals vulnerable to residual transmission from vectors that they may be exposed to outdoors. Nchelenge District in northern Zambia experiences high persistent malaria transmission even with ITNs and IRS in place. However, very few studies have examined outdoor vector activity. To assess diversity and abundance of outdoor foraging female anopheline mosquitoes, CDC light traps were used as proxy measures for mosquito host-seeking, set in three outdoor trapping schemes randomly assigned on different nights: 1) locations where people congregate at night outside of the house within the peri-domestic space, 2) animal pens or shelters, and 3) high human-trafficked areas, such as paths to latrines, where traps were baited with BG-Lure®. 1,087 total female anophelines were collected over a total of 74 trap nights. Anopheles funestus s.s. comprised the majority of the collection (86%), with An. gambiae s.s. (2%) and a highly diverse sampling of other anophelines (12%) making up the remainder. Plasmodium falciparum parasites were only detected in An. funestus (1%). No significant difference in species diversity or female anopheline abundance was detected between trapping schemes. Outdoor foraging anopheline mosquitoes, including a number of infectious An. funestus, may partially explain the difficulty of controlling malaria transmission in Nchelenge District where vector control is only targeted indoors. BG-Lure® shows some promise as an alternative to human-baited landing catch collections in this resource-poor setting.

Traumatic vascular injuries consist in direct or indirect damage to arteries and/or veins and accounts for 3% of all traumatic injuries. Typical consequences are hemorrhage and ischemia. Extremities vascular injuries can occur isolated or in association in major trauma with other organ injuries. They account for 1-2% of patients admitted to Emergency Department, for approximately 50% of all arterial injuries. Lower extremities are more frequently injured than the upper ones in adult population. The outcome of vascular injuries is strictly correlated to the environment and the time background. Treatment can be challenging notably in polytrauma because of the dilemma of which injury should be prioritized and treatment delay can cause disability or even death especially for limb vascular injury. Our purposes are to discuss the role of Computed Tomography Angiography (CTA) in the diagnosis of vascular trauma and its optimized protocol to achieve the definitive diagnosis, and to assess the radiological signs of vascular injuries and the possible pitfalls.

The objective of this work was to investigate the deacidification of bio-oils (BOs) from triglyceride-based biomass through the application of liquid-liquid extraction (LLE) in a simple stage, using methanol and water as a binary solvent and feed/solvent ratio of 1/1. For this, the effects of process parameters such as the water content present in the solvent, the content of carboxylic acids present in the bio-oil, and the extraction temperature on the deacidification process through the efficiency and distribution coefficient were evaluated, as well as the effects of such parameters on the quality of deacidified bio-oils through physical-chemical analyzes and GC-MS analysis. The results show that such process parameters significantly affect the quality of deacidified bio-oils. The ideal condition to have the highest acid removal, i.e., the highest deacidification efficiency (72.65%), is the one in which the deacidification process is performed with aqueous methanol (5% water) at 35 °C and for BOs that have a total acid number (TAN) equal to 24.38 mg KOH/g. Therefore, the process of deacidification by LLE using aqueous methanol is a promising alternative for removing carboxylic acids and other oxygenated compounds, contributing significantly to the upgrading or improving biofuels produced by catalytic thermal cracking.

The objective of this study was to detail the monomer composition of resin-based dental materials sold in the market in 2023 and to evaluate the proportion of BPA derivatives in relation with their applications. A search on manufacturers’ websites was performed to reference resin-based dental materials currently on the market. Their monomer composition was determined from material safety data sheets and completed with a search on PubMed database. Among the 543 material compositions exploitable, 382 (70.3%) contained BPA derivatives. Among them, 56.2% contained BisGMA, 28% BisEMA, the most frequently reported. A total of 59 monomers of which 6 BPA-derivatives were found. 309 materials (56.9%) contained UDMA and 292 (53.8%) TEGDMA. Less than one third of materials identified contained no BPA derivatives. These proportions vary a lot depending on their applications with materials dedicated to dental care of young populations containing the highest proportions of BPA-derivatives monomers. The long-term effects on human health of the different monomers identified including BPA-derivatives monomers is a source of concern. For children and pregnant or lactating women arises the question to take a precautionary principle and avoid the use of resin-based dental materials likely to release BPA by opting for alternative materials.

The aim of the study was to test the significance of the EPT index in the water quality assessment of three types of water bodies in hilly and mountainous region of Serbia. The aquatic macroinvertebrate community was dominated by the group of insects, of which 95 taxa represent the EPT group. We compared the obtained values of biological indices used for the assessment of water quality according to the national legislation with the overall status assessment represented by the ecological quality classes (EQC). The results of the Spearman correlation test showed a negative correlation of EQC with the EPT index, BMWP score, H', total number of taxa and number of sensitive taxa, while a positive correlation was observed for the values of SI and Tubificinae %. The values of EQC and biological indices were subjected to principal component analysis (PCA). The results showed that the parameters that contributed most to the differences were the EPT index, the BMWP score and the number of sensitive taxa. The results indicate that the EPT index is an excellent indicator of changes in water quality and an important tool for the ecological categorization of water bodies in mountain regions.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Background: Bone marrow aspiration concentrate (BMAC) has garnered increasing interest due to its potential for healing musculoskeletal injuries. While the iliac crest remains a common harvest site, the aspiration technique’s efficacy in offering the highest yield and prevalence of mesen-chymal stem cells (MSCs) is controversial. This study aimed to compare two different techniques of bone marrow aspiration over the anterior iliac crest from a single level (SL) versus multiple level (ML). Methods: Anterior iliac crests were selected in 9 adult patients (aged between 31 and 59 years old). Aspiration was achieved using an 11-gauge needle (length: 100 mm; diameter: 2.3 mm) specifically manufactured for bone marrow collection (BD, Becton, US) connected to a 10-mL syringe. On one side, 4cc of bone marrow was aspirated at an SL to a depth of 7cm without changing the needle direction. On the other side, over the same portion of the iliac crest, 1 cc of bone marrow was obtained from ML of different depths during needle retrieval, maintaining a distance of 1cm and changing the tip direction. The samples were blindly sent to the laboratory without indicating whether they came from an SL or ML. Fluorescence-activated cell sorting (FACS) and osteoblast differentiation were analyzed and compared. Results: In the FACS analysis, the SL resulted in a higher population of MSCs that were positive for CD105, CD73, and CD90 and negative for CD34, compared to the ML method. In the process of osteoblast differentiation, it was observed that MSCs exhibited more advanced features of en-hanced osteoblastic abilities in the SL method rather than the ML method. Conclusion: An SL aspiration technique at the anterior iliac crest may produce a high-quality bone marrow aspirate. This technique may help obtain specific populations of MSCs with the desired characteristics for use in regenerative therapies for musculoskeletal injuries.

Background: Chronic low-grade inflammation in obesity is linked to white adipose tissue (WAT) dysfunction. Plasma lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), triggering NF-κB and worsening these disturbances. Previously, we showed that H3K27 epigenetic modifications affect WAT gene expression in high-fat diet mice, identifying key pathways in adipose-derived stem cells (ASCs). This study explores whether NF-κB influences H3K27 modifiers in human ASCs and evaluates fish oil (FO) as a modulator. Methods: Human visceral WAT ASCs were stimulated with LPS and treated with FO enriched with eicosapentaenoic acid (EPA). Flow cytometry, PCR array, RT-PCR, and Western blot assays were used. Results: LPS increased NF-κB activity, elevating KDM6B demethylase levels and H3K27 acetylation. These epigenetic modifications in LPS-stimulated ASCs were associated with persistent changes in the expression of genes involved in adipogenesis, metabolic regulation, and inflammation, even after LPS removal and cell differentiation. FO mitigated these effects, reducing H3K27 acetylation and promoting methylation. Conclusions: FO demonstrates potential in modulating inflammation-induced epigenetic changes and preserving adipocyte function.

October 17, 2024 Dear Prof. Dr. Rizzo and Dr. Oshiro, Prof. Dr. Rizzo: Editor-in-Chief of the Endocrinology section. Dr. Oshiro: Guest Editor of the “Advances in Clinical Diabetes, Obesity, and Metabolic Diseases” special Issue. I would like to submitt the manuscript entitled “Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome in Vietnamese Patients” by Khanh Ngoc Nguyen et al. to be considered for publication as an article in the “Advances in Clinical Diabetes, Obesity, and Metabolic Diseases” of the “Medicina” journal. This study included retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. HHH syndrome is one of the rarest urea cycle disorders and is characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. Genetic analysis is key for diagnosis. In this study, we report the phenotype, genotype, treatment, and outcome of the four patients. To our best knowledge, this study is the first report of HHH patients in Vietnam. A diverse onset age and delayed diagnosis were observed. All four cases showed hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Genetic analyses identified three pathogenic variants in the SLC25A15 gene. The c.535C>T (p.Arg179*) variant is a common variant in Vietnamese patients. The c.562_564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were found in one case. The latter variant has yet been reported in the HHH patients in the literature. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, no case had hyperammonemia and liver enzyme levels returned to normal range. Our results high-lighted clinical and biochemical heterogeneity of HHH syndrome and suggested that HHH syndrome should be considered when individuals present with hyperammonemia, elevated transaminase, and decreased prothrombin time. We believe these findings will be of interest to the readers of Medicina. We confirm that neither the manuscript nor any parts of its content are currently under consideration for publication with or published in another journal. All authors approved the final version of the manuscript and agree with its submission to Medicina. Thank you for your time and effort. We look forward to hearing from you regarding our submission. Yours sincerely, Chi Dung Vu (PhD., Assoc. Prof.) Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi, Vietnam Email: dungvu@nch.gov.vn. Tel: +84-246-2747643

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause Placental Schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any sys-tematic review on PS. Methods: We conducted a systematic literature search on PubMed and in-cluded relevant secondary literature found in the citations of the primarily included publications. Results: We found a total of 8 publications describing PS with a total of 92 cases, describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association to adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only < 1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in en-demic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans. This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription–PCR (RT–qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.

This report describes the pathological findings of acute gastric dilatation syndrome in New World nonhuman primates that died suddenly. The animals were kept in a Zoo and were received proper nutritional and sanitary management. The animals were submitted for necropsy, and macroscopic findings included gastric and duodenal dilation with marked mesenteric vascular congestion. Gastric and intestinal contents were sent for microbiological examination, and bacterial colonies were isolated and identified as Escherichia coli, Streptococcus sp., Salmonella sp., Staphylococcus sp., and Cronobacter sakazakii. The antibiotic sensitivity test revealed that these bacteria had different re-sistance patterns to several antibiotics. Cronobacter sakazakii was susceptible to Ampicillin and Norfloxacin and resistant to Penicillin and Clindamycin. Cronobacter sakazakii is an opportunistic pathogen in animals, frequently reported in cases of human’s enterocolitis. Acute gastric dilata-tion, previously described in Old World nonhuman primates, is a cause of sudden death in Neo-tropical primates and should be considered as a differential diagnosis in cases of sudden mortality in these species. Although its pathogenicity in primates has not been elucidated, the isolation of Cronobacter sakazakii from samples suggests its presence in the environment, emphasizing the need for reinforced hygiene measures, especially of food supplied for these animals.

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HC) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI, and contributes to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as biomarker for disease activity.

Sewage surveillance can be used as an effective complementary tool for detecting pathogens in local communities, providing insights into emerging threats and aiding in the monitoring of outbreaks. In this study using qPCR and whole genomic sewage surveillance, we detected Mpox virus along with other viruses, in municipal and hospital wastewaters in Belo Horizonte, Brazil over a 9 months period (from July 2022 till March 2023). MPXV DNA detection rates varied in our study, with 19.6% (11 out of 56 samples) detected through the hybrid capture method of whole genome sequencing and 20% (12 out of 60 samples) through qPCR. In hospital wastewaters, the detection rate was higher at 40% (12 out of 30 samples), compared to 13.3%(4 out of 30 samples) in municipal wastewaters. This variation could be attributed to the relatively low number of MPXV cases reported in the city, which ranged from 106 to 341 cases during the study period, and to dilution effects, given that each of the two wastewater treatment plants (WWTP) investigated serves approximately 1.1 million inhabitants. Additionally, nine other virus families were identified in both hospitals and municipal wastewaters including Adenoviridade, Astroviridae, Caliciviridae, Picornaviridade, Polyomaviridae, Coronaviridae (which includes SARS-CoV-2), Herspesviridae, Papillomaviridae and Flaviviridae (notably including Dengue). These findings underscore the potential of genomic sewage surveillance as a robust public health tool for monitoring a wide range of viruses circulating in both community and hospitals environments including MPXV.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Chaotic systems can exhibit completely different behaviors given only slightly different initial conditions, yet it is possible to synchronize them through appropriate coupling. A wide variety of behaviors – complete chaos, complete synchronization, phase synchronization, etc – across a variety of systems have been identified but rely on systems’ phase space portraits, which suppress important distinctions between very different behaviors and require access to the differential equations or the full time-series. In this paper, we introduce the Difference Time Series Peaks Complexity (DTSPC) algorithm. This uses ordinal patterns created from sampled time-series, focusing on the the behavior of ringing patterns in the difference time series to quantitatively distinguish a variety of synchronization behaviors based on the entropic complexity of the populations of various patterns. We present results from the paradigmatic case of coupled Lorenz systems, both identical and non-identical and across a range of parameters and show that this technique captures the diversity of possible synchronization, including non-monotonicity as a function of parameter as well as complicated boundaries between different regimes. Thus this ordinal pattern entropy analysis algorithm reveals and quantifies the complexity of chaos synchronization dynamics, and in particular captures transitional behaviors between different regimes.

Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for a wide variety of diseases, offering the potential to modulate gene expression with a high degree of specificity. These small, synthetic nucleic acid-like molecules provide unique advantages over traditional pharmacological treatments, including the ability to target previously "undruggable" genes. Despite this promise, several biological barriers severely limit their clinical efficacy Upon administration, ASOs primarily enter cells through endocytosis, becoming trapped inside membrane-bound vesicles known as endosomes. Studies estimate that only 1-2% of ASOs successfully escape endosomal compartments to reach the cytosol, and ultimately the nucleus, where they bind target mRNA and exert their therapeutic effect. Endosomal entrapment and inefficient nuclear localization are therefore critical bottlenecks in the therapeutic application of ASOs. This review explores the current understanding of endosomal escape, and nuclear transport of ASOs. Furthermore, we examine strategies aimed at overcoming these challenges, including the use of endosomal escape agents, peptide-ASO conjugates, non-viral delivery vehicles, and nuclear localization signals. By improving both endosomal escape and nuclear localization, significant advances in ASO-based therapeutics can be realized, ultimately enhancing their potency and expanding their clinical utility

Despite their increasing prevalence epidemiological data on thoracic spine injuries(TSI) is under-presented in the literature. Furthermore, these studies fail to correlatemechanisms of injury to the specific spinal regions injured. Team ball sports appear tobe common activities undertaken in these age groups. A narrative review wasconducted to understand the aetiology of traumatic TSI, with a focus on sporting causes in youth populations. A literature search was conducted through various databases (from inception to April 2024) such as PubMed, CINAHL, Medline, ProQuest Central, Science Direct and SPORTDiscus. Seven studies, including 1670 patients were included in the dataset. TSI, particularly fractures, were found to be more common in adolescent age groups. Common sporting causes of spinal trauma included equestrian and team ball/contact sports. This review found few studies failed to correlate the mechanism of injury and the specific spinal level affected, supporting the need for further research.

In this paper we consider the standard Schur problem for a square matrix A, namely the similarity unitary transformation of A into upper Schur form containing the eigenvalues of A on its diagonal. Since the profound work of Issai Schur (1909), this is a fundamental issue in the theory and applications of matrices. Nevertheless, certain details concerning the Schur problem need further clarification especially in connection with the perturbation analysis of the Schur decomposition relative to perturbations in A. In particular, the concept of regular solution to the perturbed Schur form is introduced and illustrated by several examples. We also introduce the concepts of diagonally spectral matrices and of quasi-Schur condensed forms of a matrix A, and show that they may be much less sensitive to perturbations in A.

Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the de-generation and loss of motor neurons, leading to death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an arti-ficially synthesized short single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more opti-mized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on the overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.

Additive Manufacturing (AM) methods are increasingly beign abopted in the industry as an alternative for mass production. In particular, Fused Deposition Modeling (FDM) technology is leading the way in this field. However, the adhesion of layers in products produced using FDM technology is an important issue. These products are particularly vulnerable to forces acting parallel to the layers and specially to impact strength. This study aims to optimize the impact strength against loads acting parallel to the layers (ZX orientation) of PA6, one of the most widely used materials in the industry. This orientation is critical in term of mechanical properties, and the mechanical characteristics are significantly lower compared to other orientation. In this study, filaments containing pure PA6 with 15% short carbon fiber and 30% glass fiber were utilized. Additionally, printing temperature, layer thickness and heat treatment duration were used as independent variables. An L9 orthogonal array was employed in this study, and each experiment was repeated three times to conduct impact strength tests. Characterization, Taguchi optimization, a factor analyses were performed, followed by fracture surface characterization by SEM. As a result, the highest impact strength was achieved with pure PA6 at 8.9 kJ/m2, followed by PA6 GF30 at 8.1 kJ/m2 and the lowest impact strength was obtained with PA6 CF15 at 6.258 kJ/m2. When compared to the literature and manufacturer datasheets, it was concluded that the impact strength values have significantly increased, and the chosen experimental factors and their levels, particularly nozzle temperature, were effective.

This study aims at providing a climatological analysis of annual and long-term variability of dry periods in the Polish Carpathians in the period of 35 years between 1986 and 2020. Aside days with precipitation, dry periods, namely sequences of days with no precipitation, constitute an inherent characteristic of the climate. The input data for the research was formed by daily precipitation totals from 17 meteorological stations acquired from the Institute of Meteorology and Water Management - National Research Institute, and T. Niedźwiedź catalogue of circulation types over southern Poland. Frequency of dry periods of different duration has been presented. The incidence of long-term periods has been related to the atmospheric circulation. An analysis was performed regarding the change of the average quantity and average length of dry sequences in the 35-year period covered. At most stations, there were no statistically significant trends with respect to the analysed dry day characteristics. This is an obvious result of high variability year-to-year, which means that exclusively large changes may achieve statistical significance. Dry days have been evidenced to related to circulation types. A vast majority of dry days is related to anti-cyclonal systems, particularly the anti-cyclonal wedge (Ka) and western anti-cyclonal (Wa) situations.

This case study examined performance of rural cassava SMEs managed by small scale farmers in Busia and Kisumu Counties in the lake region of Kenya. Formal survey, focus group discussions and key informant interviews were used to collect data from farmers and stakeholders in the region. The data were analysed descriptively using proportions (percentages and proportions), means and standard deviation and inferentially, using statistical tests of significance. The findings revealed gross inefficiencies in the management of cassava SMEs. Grass-root SMEs lack professional managers and exhibit inadequate organizational, quantity and quality management, high operational costs, lack of trust from farmers, inadequate financing, weak technical, agribusiness skills and weak linkages with markets. The findings challenge promotion of farmer-led organizations in rural areas to perform additional roles such as processing and marketing functions beyond their core business which is production. To remain relevant in a competitive value chain, grass-root farmer-led SMEs need to be re structured into viable economic entities with clear market-orientation. Ordinary smallholder farmers should specialize in producing sufficient quantity and quality of agricultural commodities, while processing and marketing functions are taken up by professional entrepreneurs. This study recommends an entrepreneur model rather than farmer-led SMEs as potentially best suited in creating efficiency in the cassava value chain in the lake region of Kenya.

(1) Background: although current theories of Post-Traumatic Stress Disorder (PTSD) had focused on depressed mood and intrusion, the mechanism through which depression increases the risk of PTSD remains unclear. Research has concentrated on the hyper-active negative valence system (NVS) (e.g., increased fear and threat responses), but a significant role for hypo-active positive valence system (PVS) (e.g., less neural activation towards rewards) was conceivable. (2) Methods: To investigate the implicit processing in a refugee’s sample, ratings of arousal, dominance, and valence for 60 IAPS pictures (positive, neutral, and negative) were collected from 42 individuals with probable PTSD, and 26 trauma-exposed individuals (M age = 28.49 years, SD = ± 7.78). (3) Results: ANOVAs revealed a main group effect (η2p = 0.379) on arousal, dominance, and valence dimensions, and pictures’ categories (η2p = 0.620). Participants with PTSD responded to unpleasant images with enhanced arousal and lower valence ratings compared with individuals without PTSD. Moreover, arousal ratings were negatively correlated with valence (r = - 0.709, p &lt; 0.01). (4) Conclusions: Our findings supported evidence according to which PTSD origins a state of maladaptive hyperarousal and difficulties in regulating emotions. Positive stimuli are considered less pleasant providing evidence for a complementary involvement of NVS and PVS in PTSD development.

This mini-review discusses the development and applications of naturally derived bioconjugates from hydroxycinnamic acids, such as coumaric, sinapic, ferulic, and caffeic acids, combined with various biomaterials. These bioconjugates offer a range of benefits including antioxidant properties, UV protection, customized hydrophilic-lipophilic balance, improved safety, solubility, emolliency, biocompatibility, biodegradability, and targeted delivery for biomedical, cosmetic, and food applications. The increasing demand for sustainable and natural products in the biomedical, cosmetic, and food industries has led to the exploration of these hydroxy cinnamic acids and their derivatives. We discuss the synthesis and modification of hydroxy cinnamic acids with biomaterials such as ω-hydroxy fatty acids, castor and lesquerella oils, glycerol, isosorbides, and synthetic polyethylene glycol to form functional phenolipids for biomedical, sunscreen and skincare applications. Techniques such as encapsulation with β-cyclodextrins and modification of biopolymeric supports like polysaccharides and starch are discussed for enhancing bioavailability and solubility. The fine-tuned development of bioconjugates from hydroxycinnamic acids using glycerol to modify the hydrophilic-lipophilic balance, substitution by water-soluble carboxylic acid groups, vegetable oil-based phenolipids, polysaccharides, PEGylation provide enhanced functionalities and offers a promising avenue for creating sustainable and effective products across various applications.

Deep learning-based handwriting personality prediction uses neural networks (CNNs) to consider and predict personality characters from handwritten text to improve applications such as adaptive technology and automated data access. This method requires high computational resources and widely classified data, and its accuracy may suffer from signature variation and overfitting. This study introduces a novel optimizeddeep learning for Hand Written Personality Prediction. First the input data is collected from givendataset and an enhanced Gaussian filter is used in pre-processing to improve image quality by reducing noise and increasing contrast.After pre-processing, features are extracted by PCA-based normalized GIST, which standardizes the features to improve image representation.These extracted features are generated using an adaptive horse herd optimization algorithm to select the most important features. Based on selected features Improved Generative Adversarial Networks with artificial hummingbird optimization (IGAN_AHb) enables fast and efficient convergence of GANs. This reduce the mode collapse and ensures training with consistently fine-tuned parameters.The selected features are considered by characters such as openness, conscientiousness, extroversion, agreeableness and neuroticism, and finally classified using the IGAN_AHb classifier. In the result section, the proposed model is compared with various models with the matrix precision, recall, F1-score. The proposed model attained the value of 97.3% of precision and a recall rate of 96%, respectively. By comparing with other models, the proposed model attained highest values.

The Characteristics of the cardiac muscle cell are described as a rod-shaped structure, single nu-cleus, and intercalated discs which make the heart’s action practical for enhancing contraction ef-ficiency. Mitochondria within these cells are vital for ATP synthesis, redox balance, calcium ho-meostasis, and lipid synthesis. The crucial role of Hsp60 is in protein folding and immune re-sponses; Hsp60 is a mitochondrial chaperonin, and its expression rises when the heart is under a stress condition like myocardial infarction and heart failure. This review has tried to deeply un-derstand the structural resemblance between cardiac and skeletal muscle cells, the amplitude number of mitochondria, its roles in cardiomyocytes, and the polyhedral functions of Hsp60. In this review, by investigating various articles, we brighten up Hsp60's distribution within cells, its association with apoptosis, and its action as a Damage Associated Molecular Pattern (DAMP), interacting with Toll-like receptors to modulate immune responses. Cardiac remodeling and failure are linked to cardiac-specific micro-RNAs whose expression may be affected by dysregu-lation of Hsp60. In conclusion, targeting mitochondrial function and Hsp60 expression may be of therapeutic potential for heart diseases.

This paper focuses on the role of the most common mineralogical techniques applied to the identification of the different statuary qualities in white, grey and black Göktepe marble. For this purpose, a Roman case of sculpture marble collection from the rural villa of Valdetorres de Jarama (central Iberia), of the 4th century AD, is presented. The mythological statuary, combining white, grey and black marbles, are one of the most outstanding marble collections in Aphrodisian style found in Hispania. The analytical results (Petrography, Cathodoluminescence, C and O isotopes, and Sr and Mn concentration) support the identification of two varieties of “black” Göktepe, traditionally named as bigio morato and bigo antico, as well as the best statuary quality on white Göktepe. In addition, the analytical identification of other Asiatic marbles in Valdetorres collection, a white coarse-grained originally from the quarries of Aphrodisias city and one small piece identified as Carian red from Iasos, corroborates the already suggested strong connection existing between artists and the stone material they chose for their works. Finally, it is noteworthy the identification carried out on the marble of the bases that served as seats for the sculptures, as it is a white marble of lower quality whose analytical characteristics are consistent with the Microasiatic marble of Denizli. The use of these exotic and exceptional raw materials confirms the taste for luxury and decorative richness in Late Antique Hispanic rural villae and contributes to a better understanding of the distribution of Aphrodisian productions in the Western Roman provinces.

Vaccine hesitancy has emerged as a significant barrier to achieving herd immunity and protecting populations from preventable diseases. Despite the proven effectiveness and safety of vaccines, many individuals remain hesitant or refuse to vaccinate themselves or their children. This review aims to identify the factors contributing to vaccine hesitancy, including misinformation, lack of trust in authorities, cultural beliefs, and access barriers. We also discuss the impact of vaccine hesitancy on public health, including outbreaks of vaccine-preventable diseases and erosion of trust in public health authorities. Furthermore, we present evidence-based communication strategies for addressing vaccine hesitancy, including building trust, providing accurate information, addressing myths and misconceptions, engaging with local influencers, and utilizing social media and digital platforms. By understanding the factors contributing to vaccine hesitancy and implementing effective communication strategies, healthcare providers, public health officials, and community leaders can work towards promoting widespread vaccine acceptance and protecting public health.

Industrial robots are slowly but surely entering manufacturing companies. This paper explores the effects that robots have on productivity, exports, quality, sustainability and labor in European manufacturing companies. There is lack of research on industrial robot usage and its effects in developed countries. Most research is done on Chinese companies and often the data is outdated. The data in this paper is from the European Manufacturing Survey project conducted in 2022 and includes 476 manufacturing companies. Results of the effects of Industrial robots on Quality, Labor Productivity, Exports and Environmental saving technologies are done by use of T-test between industrial robots’ adopters and non-adopters. However, the effect of higher investment into environmental technology by industrial robots’ adopters was researched by 2-step OLS regression analysis with control variables representing the contextual characteristics of companies. The results show positive effects on all variables. Results show that larger usage of robots are in low to medium-technology-intensity industries, that robots contribute to labor productivity, exports and that companies employing robots usually also employ environmentally saving technologies.

This article discusses collaborative ethnography as a meaningful source for spatial research, in particular, for participatory methodologies in urban planning and placemaking processes. It investigates the experiences with co-creation and co-research in different research projects to gain insight into the performance of collaborative ethnography as a technique to explore and enrich local knowledge. To better understand the possible causal relationships between the experience gained in the projects and the learnt lessons, we also identify recommendations for improving research methodologies to be applied in placemaking. The article concludes that collaborative ethnography is an effective tool for adding value to spatial co-research and co-creation processes. It opens opportunities for the co-production of space, ideas and knowledge, contributing at the same time to better informed decision-making. It also helps improve ideas and gather insights into the spatial needs of focus groups.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

This study addresses the formidable challenge of solving large-scale Max-Cut problems (MCP). We introduce a rapid computational procedure utilizing a hybrid 1-flip/r-flip local search heuristic. This innovative strategy significantly reduces the computational time required for MCP problems while consistently generating solutions of exceptional quality. The paper presents substantial computational insights, showcasing the effectiveness of our approach on large-scale Max-Cut instances with varying densities. Our proposed heuristic is rigorously evaluated by comparing its performance against a quantum annealing solver, leveraging a multi-start Tabu Search framework. The results underscore the potency of this unique combination as an efficient and effective solution for large-scale QUBO problems. Notably, our hybrid heuristic consistently delivers high-quality solutions within the stringent CPU time limits of 600 seconds, demonstrating its efficacy across Max-Cut instances ranging from 10,000 to 40,000 variables. This research contributes to advancing the state-of-the-art in large-scale QUBO problem-solving, offering a powerful and time-efficient approach with broad applicability.

This paper proposes a methodology for the development and its Verification and Validation(V&amp;V) of safety-rated software. The development methodology is based on the structured analysis and structured design methodology, which has been proven in the field of safety software development during long period. The suggested the development and the V&amp;V methodology additionally focuses on the quality attributes 3C+T (completeness, Correctness, Consistency and traceability), which are important criteria in IEC international standards. The software development life cycle is compiled from IEC international standardization, which are of the requirements analysis phase, design phase, implementation phase, testing phase, installation/commissioning phase, and operation &amp; maintenance phases. The activities of the development process method were defined from requirements analysis to implementation, and the activities of the verification and validation were defined to include the scope of the developer's activities and then to include the test phase, installation/commissioning phase, and operation phases additionally. In other words, testing phase performed by the developer was defined as informal testing, and testing performed by the verifier according to test criteria, test plans, and test procedures was defined as formal testing. According to proposed methodology, the requirements phase defines the sequence of Entity Relationship Diagram (ERD)-Context Diagram-Data Flow Diagram (DFD), functional decomposition process and defines operational scenario. In the design phase, module design such as task analysis and task allocation were defined. In the implementation phase, we listed the coding guidelines that must be followed for safety-related system. The test phase defined the test criteria, test plan, test procedure, and test result report activities. In the installation/commissioning and operation phases, recommendations for improving reliability, quality, and safety were proposed for deliverables such as user documentation and technical documentation.

Steel fibre reinforced concrete (SFRC) consists of short hooked steel fibres randomly distributed and oriented within the cementitious matrix. The contribution of fibre in bridging cracks to provide the stress transfer required relies upon the orientation of the fibre in the concrete. Bridging fibre aligned with a crack are less effective than those inclined to it. Therefore, understanding the pull-out behaviour of misaligned fibre is a key factor to quantify and optimize the design of SFRC in the structural applications. In the laboratory a single oriented fibre embedded in a solid cylinder of concrete is subjected to a pull-out test where the axis of a tensile force is aligned with the axis of the cylinder. Based upon the observed behaviour this paper presents a new analytical bounding approach to capture the pull-out response of misaligned hooked-end steel fibre embedded in a concrete matrix. The analysis is based upon a transversely isotropic condition assumed for the plasticity that occurs in the cold drawn fibre. The model accounts for the influence of fibre diameter and the combined strengths of the steel and concrete. The model predictions have also been compared with other experimental results published in the literature. The results showed that the model can predict pull-out loads reasonably for different fibre orientations between bounds of failure derived from the strengths of the two constituents. A critical orientation is observed at maximum strength. Therein, an understanding of the pull-out behaviour of misaligned, hooked-end fibres is necessary to optimize the strength of concrete from this method of reinforcement.

Recently, microfluidics deformability cytometry has emerged as a powerful tool for high throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints through exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids such as methyl-cellulose dissolved in phosphate-buffered saline is significantly influential to the resulting cellular deformation. We conducted CFD simulations that are conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e. HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses.

In today's intricate media landscape, the resilience and relevance of public service media (PSM) depend on their capacity to align with the diverse and evolving expectations of the public. However, the audience perspective is often overlooked, resulting in a limited understanding of public expectations. This study employs a bottom-up approach that allows for a re-evaluation of the expectations from the audience's viewpoint. It investigates the public's expectations for PSM, drawing on data from 10 focus group discussions (with 60 participants) conducted in the Czech Republic. The findings indicate that expectations can be categorized into four primary dimensions: (1) the expected roles and functions of PSM; (2) the general characteristics of the PSM content (defining the desired nature of PSM content); (3) the principles governing the functioning of PSM (outlining how PSM should operate); and (4) specific requirements concerning PSM news and non-news content. In the latter dimension, objectivity emerged as one of the most critical expectations and a major source of dissatisfaction. While participants collectively value objectivity, they disagree on its definition. A deeper examination revealed that certain public expectations may be unattainable due to the simplistic view of objectivity held by some.

Lettuce (Lactuca sativa) is a leafy vegetable that provides a valuable source of phytonutrients for a healthy human diet. Assessment of plant growth and composition is vital for determining crop yield and overall quality, however, classical laboratory analyses are slow and costly. Therefore, new, less expensive, more rapid, and non-destructive approaches are being developed, including those based on (hyper)spectral reflectance. Additionally, it is also important to determine how plant phenotypes respond to fertilizer treatments and whether these differences in response can be detected from analyses of hyperspectral image data. In the current study, we demonstrate the suitability of hyperspectral imaging in combination with machine learning models to estimate the content of chlorophyll (SPAD), anthocyanins (ACI), glucose, fructose, sucrose, vitamin C, β-carotene, N, P, K, dry matter content, and plant fresh weight. The implemented five classification and regression machine learning models showed high accuracy in classifying the lettuces by the applied fertilizers treatments and estimating nutrient concentrations. To reduce the input (predictor data, i.e., hyperspectral data) dimension, 13 principal components were found and applied in models. The implemented artificial neural network models of the machine learning algorithm demonstrated high accuracy (r = 0.85 ... 0.99) in estimating fresh leaf weight, and contents of chlorophyll, anthocyanins, N, P, K, and β-carotene. The four applied classification models of machine learning demonstrated 100% accuracy in classifying the studied baby leaf lettuces by phenotype when certain fertilizer treatments were applied.

Three species of subfamily Cultrinae currently live in Korea, but Erythroculter erythropterus has been introduced into the Nakdonggang River and has taken over the habitat, reducing the habitat of Culter brevicauda. Only the endangered species C. brevicauda still lives in the Yeongsangang River, and it is necessary to be careful not to introduce E. erythropterus in the future. And Hemiculter eigenmanni is also found throughout the country. In order to effectively manage and conserve the species in its various habitats and against invasions, this study was initiated. The ultrastructure of the egg envelopes of three species of Cultrinae— E. erythropterus, C. brevicauda, and H. eigenmanni, inhabiting the Geumgang and Yeongsangang Rivers were observed. It was found that the zona radiata of the egg envelopes of all three species were divided into two layers–an outer and inner layer, with the outer surface having a non-structural form. This form is characteristic of fishes with muddy, stagnant habitats or spawning grounds. The number of pore canals on the surface of the egg envelopes was 83 for E. erythropterus, 75 for C. brevicauda, and 58 for H. eigenmanni per 10 ㎛2, and the thickness was 7.89±0.34 ㎛, 12.27±0.46 ㎛, and 7.42±0.24 ㎛, respectively. The shape of the micropyle demonstrated a funnel shape narrowing toward the inner diameter in all three species, and the size of the inner diameter was 6.62±0.29 (6.09~7.10) ㎛ in E. erythropterus, 4.19±0.39 (3.39~4.58) ㎛in C. brevicauda, and 3.98±0.46 (3.47~4.93) ㎛in H. eigenmanni. The differences between species were identified in the number of pore canals, thickness, and micropyle inner diameter of egg envelopes, which were species-specific. Our study revealed a morphological mechanism in the egg envelope that prevents the formation of interspecific hybrids, and these features can be taxonomic traits that clarify species names. It also provided useful data for the production (breeding) of the second generation in aquaculture.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

With the aging of China's population, the problem of pension security has become more and more prominent, and whether delayed retirement can effectively alleviate the pension fund gap and ensure the sustainability of the pension fund has become the focus of social concern. This study predicts the income and expenditure of urban workers' basic pension insurance fund from 2021 to 2050 by constructing an actuarial model of pension insurance fund income and expenditure, and simulates the effect of delayed retirement policy. The prediction results show that under the existing system, the basic pension insurance fund for urban workers will have a shortfall for the first time in 2027, and the shortfall will expand year by year. Compared with the non-implementation of delayed retirement policy, the simulation of the implementation of delayed retirementt program delayed the emergence of the fund gap until 2029, and the forecast period of the pension fund gap significantly narrowed, indicating that delayed retirement policy has a certain positive impact on alleviating the pressure of pension payments, but delayed retirementt can not completely eliminate the pension fund gap. In view of this, this paper suggests that a progressive and flexible delayed retirement policy should be introduced as soon as possible to better adapt to the needs of different groups. At the same time, differentiated policies should be formulated for different groups of people and a pension incentive mechanism for delayed retirement should be set up to improve public acceptance of delayed retirement policy. In addition, delayed retirement policy should be combined with other measures, such as lowering the corporate contribution rate and enhancing the value-added capacity of the pension fund, so as to ensure the sustainability of the pension fund.

Microwave radiation diagnosis technology can detect thermal changes in skin tissue earlier than anatomical changes, but its detection accuracy is limited by non-target radiation interference in the measurement environment, additional measurement errors of system units, and energy scattering and transmission between skin tissues. This paper aims to address the scientific challenges of analyzing the forward and inversion modelling detection mechanism of layered accurate temperature measurement of human skin tissue based on multi-band. The study focuses on the construction of a pencil beam antenna optimization system, the optimization strategy of high-sensitivity correlated radiometer architecture, and the high-precision multi-band forward and inversion modelling detection algorithm. The key technologies include: (1) A new method of integrated modeling and multi-index optimization of antenna with high directivity and small aperture is proposed, and a priori knowledge-guided neural network of pencil beam distribution is constructed to realize the inversion model of antenna structural parameters; (2) The influence mechanism of high sensitivity correlated radiometer architecture error is analyzed, and a periodic phase shift error correction algorithm based on uniform polar circle is designed; (3) Combining deep learning theory and hyperparameter optimization framework, an iterative model is established, and the objective function modified by the penalty factor is defined to realize a new detection method combining forward and inversion. This paper presents a theoretical foundation for the industrialization of microwave radiation diagnostic technology.

It is concerning that Cameroon's urban centers are experiencing an alarming rise in air pollution as a result of urbanization, population growth, industrial activity, and transportation emissions. We examined the causes, health impacts, research methodology, case studies, and government measures to address the urgent issue of air pollution in Cameroon's urban regions. We have emphasized how Cameroon's air pollution levels have significantly increased as a result of causes like population expansion, urbanization, industrial emissions, and automobile exhaust A thorough discussion of the negative health impacts of extended exposure to air pollution is included, with special attention to the sensitivity of the old and young. These effects include respiratory disorders, cardiovascular ailments, and early mortality. We emphasized the pressing need for all-encompassing strategies to address air pollution, such as increased public awareness campaigns, stronger emissions regulations, the development of renewable energy sources, and better waste management. The techniques employed in studies on air pollution, like as epidemiological research and air quality monitoring, are also explained to provide light on the unique health dangers that Cameroonian urban dwellers must contend with. We emphasized in our conclusion the significance of joint efforts by legislators, medical professionals, and the general people to reduce air pollution and protect public health in Cameroon in order to create a cleaner and healthier future. In order to protect public health in the future, it is imperative that Cameroon's air pollution be addressed.

Medical data flows in streams as the data related to clinical tests and administered drugs by the doctors flows continuously. The doctors must be immediately alerted if negative associations are found among the drugs they prescribe. Data streams are to be processed in single scans as it is not possible to re-scan the data for any iterative processing. To detect negative drug connections, regular and frequent drug patterns must be processed. Negative correlations between disease-curing medications might create adverse responses that kill patients. This paper proposes an algorithm that finds the negative associations among regular and frequent patterns mined from medical data streams. The negative associations mined are the most effective and reduce the negative associations, which are more critical by 50%.

The main characteristic of polycystic kidney disease is the development of multiple fluid filled renal cysts. The discovery of mislocated Na,K-ATPase in the apical membrane of cyst lining epithelia alluded to a reversal of polarity as a possible explanation to the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical t-SNARE protein Syntaxin-3 also immunolocalized to the apical domain of cyst lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst lining epithelia in polycystic kidney disease.

The results of the investigation showed that second-order kinetics govern the adsorption process, and the corresponding rate constants were found. To evaluate the parameters related to the adsorption process, the adsorption equilibrium was examined using a variety of mathematical models, such as the Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich isotherm models. The Langmuir isotherm was found to be the best appropriate among all models for describing the adsorption of Cu2+ and Ni2+ ions using bio-nanocomposite beads. The positive values of ΔH° indicate that the adsorption is physical and endothermic, in agreement with experimental results. The negative value of ∆G° shows that the adsorption process is spontaneous. Positive ΔS° values indicate increased randomness at the solid/liquid interface, during adsorption of Cu2+ and Ni2+ cations onto the engineered bio-nanocomposite. The maximum adsorbed amounts of metal ions by the bio-nanocomposite used were 370.37 mg/g for Ni2+ and 454.54 mg/g for Cu2+ from single system. For the binary system, according to the Langmuir isotherm, the maximum adsorbed amounts of Ni2+ and Cu2+ were 357.14 mg/g and 370,37 mg/g, respectively. There is proof that Alginate-Moroccan clay bio-nanocomposites can serve as a different, less expensive source of sorbents for the removal of metal ions from single and binary systems.

Cassava (Manihot esculenta Crantz), domesticated in the Amazonian region of South America, presents an important diversity in Ecuador, where it is a main staple food; however, only few Ecuadorian cassava accessions have been included in international molecular assessments. The purpose of this study was to apply suitable cassava mi-crosatellites to characterize the genetic variability of the Ecuadorian cassava collection composed mainly of local landraces from the Coast, Andes and Amazonia regions. The use of microsatellite markers allowed the determination of the genetic diversity of the collection. Seven selected SSR primers, permitted to identify homozygous and hetero-zygous materials within the cassava collection of 133 accessions. The loci presented an average genetic diversity value of 0.7 and an average PIC value of 0.67, which is con-sidered high. Low number of duplicates (8.8%) were identified in the Ecuadorian col-lection which is not fully duplicated at CIAT. Currently, a wide range of cassava diver-sity is still cultivated in multi-crop agro-ecosystem, mainly in the Coast and Amazo-nian regions. Especially in the Amazonian region, due to important cultural uses of cassava by local ethnic communities, more in depth studies in the region could unveil the genetic diversity present in situ today.

Abstract: Safety issues related to the electrification of more electric aircraft (MEA) need to be addressed because of the increasing complexity of aircraft electrical power systems and the growing number of safety-critical sub-systems that need to be powered. Managing the energy storage systems and the flexibility in the load-side plays an important role in preserving the system’s safety when facing an energy shortage. This paper presents a system-level centralized operation management strategy based on model predictive control (MPC) for MEA to schedule battery systems and exploit flexibility in the demand-side while satisfying time-varying operational requirements. The proposed online control strategy aims to maintain energy storage (ES) and prolong the battery life cycle, while minimizing load shedding, with fewer switching activities to improve devices lifetime and to avoid unnecessary transients. Using a mixed-integer linear programming (MILP) formulation, different objective functions are proposed to realize the control targets, with soft constraints improving the robustness of the model. Besides, an evaluation framework is proposed to analyze the effects of various objective functions and the prediction horizon on system performance, which provides the designers and users of MEA and other complex systems with new insights into operation management problem formulation.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

Local polynomial smoother (LPS) is a weighted local least-squares nonparametric method. It provides a local Taylor series fit of the data at any location and can be directly used in a differential equation to provide a numerical scheme. In this article, we introduce this new nonparametric idea based on local polynomial smoother, for acquiring the numerical solution of the Bagley-Torvik fractional-order differential equations. Furthermore, this paper will present a numerical comparison with some methods, such as legendre operational matrix and pseudo-spectral method. The efficiency and accuracy of the LPS method are demonstrated by two numerical examples.

To evaluate new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C), among them, 22 presented MVC. Pe-ripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid pe-roxidation, LPO). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to CG. DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased for miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive value for vascular complications presence: 1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484. 2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484. Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values than classical variables. miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.

We present a synchronization transition study of the locally coupled Kuramoto model on extremely large graphs. We compare regular 405 and 1004 lattice results with those of 120002 lattice substrates with power-law decaying long links (ll). The latter heterogeneous network exhibits ds&gt;4 spectral dimensions. We show strong corrections to scaling and mean-field type of criticality at d=5, while logarithmic corrections at d=4. Contrary, the ll model exhibits a non-mean field smeared transition, with oscillating corrections, suggesting the network heterogeneity is relevant, causing frustrated synchronization, akin to Griffiths effects.

Sustainable soil resource management requires detailed knowledge of soil pollution sources and their share in total pollution level. Spatial pollution caused by the total cumulative atmospheric deposition remains largely unknown, as the biggest pollutant emissions occurred in XIX/XX centuries. The use of ombrotrophic peatlands that are specific isolated ecosystems fed only through atmospheric deposition may serve as its natural archives. Accumulation of Cd and Pb from atmospheric deposition in undisturbed soil layers in relation to their total deposited cumulative loads recorded in the ombrotrophic peat bog was exemplified in the Izera Mountains. area historically heavily affected with the transboundary long-range transmission of pollutants from Germany, Czech Republic and Poland. Balance of deposited Cd and Pb loads in soil in relation to the total cumulative deposition determined from peat records, showed 30% depletion of Cd load in the soil profile due to washout of mobile phases, while that of Pb practically did not decline. The deposited element accumulation and release/depletion in undisturbed soil profiles can thus be quantified in relation to the total cumulative load of atmospheric deposition. This shows a new prospective application of peat bog records as monitors of total cumulative loads of trace elements supplied to soils from atmospheric deposition.

In a series of publications, we attempt to demonstrate the prophylactic role of bromhexine hydrochloride (BHH) and the curative role of high colchicine doses against COVID-19. Effects of long-term prophylaxis with BHH are presented in two cases of elderly women with severe comorbidity. After long-term prophylactic use of BHH from 3 to 6 months, one does not get sick from COVID-19, and the other passes it almost asymptomatically, even though all their family members fall ill. The dramatic healing effect of colchicine was demonstrated in a family in which both spouses became ill with COVID-19 almost simultaneously. They are treated in different hospitals, and where colchicine is administered in high doses, the patient recovered. The other patient developed complications and died on standard treatment without high doses of colchicine. An outpatient accidentally overdosed on colchicine (12.5mg). The therapy was stopped immediately. Clinically, on the third day, there are absolutely no symptoms. These cases reaffirm the prophylactic effect of BRH and the curative effect of high-dose colchicine

Background: Traditional root canal therapy (RCT) has been the primary method for treating necrotic pulp, but it presents limitations such as loss of vitality and postoperative fractures. Recent advancements in regenerative endodontics offer alternative strategies to restore pulp tissue vitality and function. These approaches involve stem cell transplantation, cell homing, and the use of organic scaffolds to promote pulp regeneration. Highlight: This article reviews various regenerative endodontic techniques, including autogenic and allogenic dental pulp transplantation, the use of amniotic membrane scaffolds, platelet-rich fibrin therapy, specialized pro-resolving mediators, nanofibrous and bioceramic-based scaffolds, injectable scaffolds, and dentin matrix proteins. These strategies leverage stem cells, growth factors, and biomaterials to create conducive microenvironments for cell attachment, proliferation, and differentiation, thereby facilitating pulp tissue regeneration. Methods: The literature search was conducted using databases such as PubMed, Scopus, and Google Scholar, employing keywords like "regenerative endodontics," "pulpitis," "pulp regeneration," and "platelet-rich fibrin." Conclusion: The reviewed approaches in regenerative endodontics show promising potential for overcoming the limitations of traditional RCT and promoting pulp tissue regeneration. However, further research is needed to optimize protocols, address challenges, and translate these advancements into routine clinical practice. Ultimately, these innovations have the potential to enhance patient outcomes in endodontic treatment by restoring pulp vitality and function effectively.

Land cover refers to the combination of various material types and their natural characteristics on the Earth. Accurately mapping the spatial distribution and temporal changes of the earth's land cover is of great significance for studying the energy balance and carbon cycle of the earth system. However, there is still a high degree of human participation in the production of multi-temporal land cover products. Developing an automated method for multi-epoch land cover mapping has become a key research focus. To this end, an automatic training sample extraction method was first employed using multi-source prior land cover products. Then, based on the generated training dataset and the Random Forest classifier, local adaptive land cover classification models of the reference year were developed. Finally, by migrating the classification model to the target epoch, the multi-epoch land cover products were generated. Yuli County in Xinjiang and Linxi County in Inner Mongolia were used as test cases. The classification models were first generated in 2020 and then transferred to 2010 to enable automatic classification of multi-temporal land cover. The mapping results showed high accuracy in both regions, with Yuli County achieving 92.52% in 2020 and 88.33% in 2010, and Linxi County achieving 90.28% in 2020 and 85.28% in 2010. Additionally, uncertainty analysis of the model migration method revealed that land types such as water bodies, wetlands, and impervious surfaces, which exhibit significant spectral changes over time, are less suitable for the model migration. Our research can offer valuable insights for fine-resolution land cover mapping. Furthermore, the approach provides a scalable solution for multi-period land cover monitoring, which could facilitate more efficient and accurate environmental assessments.

Background: Studies on infectious endocarditis (IE) are mostly limited to institutions, which highlights the need for more comprehensive epidemiological studies. Objective: To verify the profile of deaths due IE and the relationship with deaths from other causes and conditions in Brazil and regions. Method: Study in database from the Brazilian Mortality Information System, from 2000 to 2019. Mentions of deaths due to IE, other causes and conditions were identified according to ICD-10. Cluster analysis was performed to verify the relationship between variables. Results: 52,055 deaths from IE were found, with a predominance of males, aged 60 to 79 years, in the Southeast, with deaths from the circulatory system most frequent. Three profiles were identified: 1 - age equal to or greater than 80 years, women, deaths due endocrine, circulatory and metabolic diseases, in the South and Southeast; 2 - also in the South and Southeast, age between 30 and 79 years, men, deaths due infectious and genitourinary diseases; 3 - 0 to 29 years, no genders differences, deaths due diseases of the respiratory system, in the North, Northeast and Central-West. Conclusion: Cluster analysis showed diversity in the profiles of deaths due IE, indicating heterogeneity in regions of the country.

An innovative approach is utilized in this paper to solve the Fractional Fokker–Planck–Levy (FFPL) equation. A hybrid technique is designed by combining the finite difference method (FDM), Adams numerical technique, and physics-informed neural network (PINN) architecture, namely, the FDM-APINN, to solve the fractional Fokker‒Planck‒Levy (FFPL) equation numerically. Two scenarios of the FFPL equation are considered by varying the value of α (i.e., 1.75,1.85). Moreover, three cases of each scenario are numerically studied for different discretized domains with 100,200 and 500 points in x∈[-1,1] and t∈[0,1]. For the FFPL equation, solutions are obtained via the FDM-APINN technique via 1000,2000, and 5000 iterations. The errors, loss function graphs, and statistical tables are presented to validate our claim that the FDM-APINN is a better alternative intelligent technique for handling fractional-order partial differential equations with complex terms. FDM-APINN can be extended by using nongradient-based bioinspired computing for higher-order fractional partial differential equations.

The production of high stiffness Ti-based Metal Matrix Composites (Ti-MMCs) displaying significant ductility by additive manufacturing technologies is not yet at the level of conventionally produced Ti-MMCs. This study outlines the production process of stiffness-driven Ti-TiC MMCs displaying a remarkable ductility. The process consists in powder Mechanical Blending, Laser Powder Bed Fusion (LPBF), and a heat treatment. A TiC fraction of more than 20 vol% was formed in-situ through the reaction of titanium with carbon during the LPBF process. The as-built sub-stoichiometric TiC dendrites are converted in equiaxed TiC grains during the heat treatment. The TiC C/Ti ratio was found to be close to 0.5 in as-built conditions, and 0.7 in heat treated conditions, resulting in an effective reinforcement content nearly twice the one expected for stoichiometric TiC, leading to stronger reinforcement. The mechanical analysis revealed a Young’s modulus of up to 149 GPa and total elongations of up to 2.8%. The former represents a 27% improvement compared to commercially pure Titanium and the latter exceeds by 115% reported values for LPBF Ti-MMCs with similar Young’s modulus. It is enabled by the in-situ formation of defect-free TiC reinforcements combined with their globularisation through heat treatment.

The COVID-19 pandemic has significantly impacted human health and daily life. Meteorological factors play a crucial role in virus transmission. Understanding these factors is critical for pandemic control, yet debates continue due to variations in research methods and data. This study uses a global dataset and focuses on administrative units smaller than 10,000 km². The relationship between daily COVID-19 incidence rates and meteorological factors—including temperature, relative humidity (RH), ultraviolet radiation (UVR), and diurnal temperature range (DTR)—was analyzed across 173 units in 62 countries. The results revealed significant nonlinear responses and lag effects between incidence rates and the meteorological factors. Key inflection points were observed at 0°C and 24°C for temperature, 63% for RH, 102 KJ/m² for UVR, and 15°C for DTR. Below 0°C, infection risk increased with rising temperatures; from 0°C to 24°C, risk decreased; and above 24°C, risk escalated rapidly. RH below 63% correlated inversely with infection risk, while above 63%, the correlation was positive. Infection risk decreased with UVR below 102 KJ/m² but increased beyond this threshold. These nonlinear responses are primarily driven by the differential effects of these factors on virus survival, transmission, and human immunity. Conditions around 24°C, 63% RH, 102 KJ/m² UVR, and DTR below 15°C appear optimal for human immunity, correlating with lower infection risk. High temperature and low UVR prompted immediate infection responses, while low temperatures, high UVR, and larger DTR showed delayed effects. These findings provide new, more reliable evidence for understanding the mechanisms driving COVID-19 pandemic dynamics and for preventing the future normalization of the epidemic.