Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Cementitious materials exhibit excellent binding properties and micropore structures that support the stabilization of TiO2 nanoparticles within the matrix. Therefore, these materials are ideal for the development of functional construction products with TiO2 nanoparticles. This study investigated the degree of hydration, microstructure, and mechanical properties of cement-containing TiO2 nanoparticles. The experimental results demonstrated that TiO2 nanoparticles accelerated the hydration rate of cement, reducing the setting times. Moreover, TiO2 nanoparticles changed matrix microstructure, decreasing the porosity and improving early-age strength. Although TiO2 nanoparticles function as nucleation sites in the cement hydration reaction, the tendency of the particles to clump implies that proper dispersion should be ensured when mixing in large quantities. When developing new building materials incorporating TiO2 nanoparticles, considering the effect of TiO2 nanoparticles on the hydration reaction of cementitious materials is crucial.

In this study, a novel method is proposed to estimate surface-spectral reflectance from camera responses that combines model-based and training-based approaches. An imaging system is modeled using the spectral sensitivity functions of an RGB camera, spectral power distributions of multiple light sources, unknown surface-spectral reflectance, additive noise, and a gain parameter. The estimation procedure comprises two main stages: (1) selecting the local optimal reflectance dataset from a reflectance database and (2) determining the best estimate by applying a neural network to the local optimal dataset only. In stage (1), the camera responses are predicted for the respective reflectances in the database, and the optimal candidates are selected in the order of lowest prediction error. In stage (2), most reflectance training data are obtained by a convex linear combination of local optimal data using weighting coefficients based on random numbers. A feed-forward neural network with one hidden layer is used to map the observation space onto the spectral reflectance space. In addition, the reflectance estimation is repeated by generating multiple sets of random numbers, and the median of a set of estimated reflectances is determined as the final estimate of the reflectance. Experimental results show that the estimation accuracies exceed those of other methods.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

The rapid advancements in satellite technology have led to a significant increase in high-resolution remote sensing (RS) images, necessitating advanced processing methods. Additionally, a patent analysis revealed a significant increase in deep learning and machine learning applications in remote sensing, highlighting the growing importance of these technologies. Therefore, this paper introduces the Kolmogorov-Arnold Network (KAN) model to remote sensing, aiming to enhance efficiency and performance in RS applications. We conducted several experiments to validate KAN's applicability, starting with the EuroSAT dataset, where we combined the KAN layer with multiple pretrained CNN models. The optimal performance was achieved with ConvNeXt, leading to the development of the KonvNeXt model. KonvNeXt was evaluated on the Optimal-31, AID, and Merced datasets for validation, and it achieved accuracies of 90.59%, 94.1%, and 98.1%, respectively. The model also showed fast processing speed, with the Optimal-31 and Merced datasets completed in 107.63 seconds each, while the bigger and more complicated AID dataset took 545.91 seconds. This result is meaningful since it achieved faster speeds and comparable accuracy compared to the existing study which utilized VIT and proved KonvNeXt's applicability for remote sensing classification tasks. Furthermore, we investigated the model's interpretability by utilizing Occlusion Sensitivity and by displaying the influential regions, it validated its potential use in a variety of domains including medical imaging and weather forecasting. This paper is meaningful in that it is the first use of KAN in remote sensing classification, proving its adaptability and efficiency.

The teaching of mathematics at the Faculty of Military Technology of the University of Defense in the first two years of the five-year Military master’s degree is divided into the teaching of students in four specializations: Military Technologies – Mechanical, Military Technologies – Electrical, Military Geography and Cartography, and Cybersecurity. The article discusses the previous five-year experience in teaching the subjects Mathematics I, Mathematics II, Mathematics III, and Graph theory for the specialization in Cybersecurity, that the author of the paper gained while teaching, as a guarantor of these four subjects. The article provides an overview of the topics that are covered, typical exam assignments, and an evaluation of the results of the semester exams in the five years since the accreditation of the Cybersecurity specialization was granted.

Clustered regularly interspaced short palindromic repeats (CRISPR) based gene-editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single guide RNA (sgRNA)-based gene-editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, instructive, and inspiring for future advances. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent beta thalassemia has renewed hope for treating other hematologic diseases, including patients with germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-based gene therapies. The purpose of this manuscript is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy; and third, the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with germline predisposition to hematologic malignancies.

The thermal surface properties of graphenes and carbon materials are of crucial importance in chemistry of materials, chemical engineering, and many industrial processes. (1) Background: The determination of these surface properties is carried out using inverse gas chromatography at infinite dilution which leads to the retention volume of organic solvents adsorbed on solid surfaces. This experimental and fundamental parameter actually reflects the surface thermodynamic interactions between injected probes and solid substrates. (2) Methods: The London dispersion equation and the Hamieh thermal model were used to quantify the London dispersive and polar surface energy of graphenes and carbon fibers as well their Lewis acid-base constants by introducing the coupling amphoteric constant of materials. (3) Results: The London dispersive and polar acid-base surface energies, the free energy of adsorption, the polar enthalpy and entropy, and the Lewis acid-base constants of graphenes and carbon materials were determined. (4) Conclusions: it was showed that graphene exhibited the highest values of London dispersive surface energy, polar surface energy, and Lewis’s acid-base constants. These highest characteristics of graphene justify its great potentiality and uses in many industrial applications.

The global steel industry is a major contributor to greenhouse gas emissions, and the adoption of green hydrogen in Direct Reduced Iron (DRI) production has the potential to significantly reduce CO2 emissions and support climate targets. This review explores the environmental, economic, technological, and social implications of using green hydrogen in DRI processes. The findings suggest that green hydrogen can reduce emissions by up to 90% compared to traditional methods, enhance energy security, and stimulate local economic development. However, high initial costs, energy efficiency concerns, and social acceptance issues remain significant barriers. The review also highlights the importance of integrating carbon capture and storage technologies, addressing logistical challenges, and considering the geopolitical implications of a shift towards green hydrogen. Green hydrogen presents a promising solution for decarbonising the steel industry but continued research, investment in infrastructure, and strategic planning are essential to overcome the challenges and drive widespread adoption.

We consider fractional integral operators $(I-T)^d, d \in (-1,1)$ acting on functions $g: \mathbb{Z}^{\nu} \to \mathbb{R}, \nu \ge 1 $, where $T $ is the transition operator of a random walk on $\mathbb{Z}^{\nu}$. We obtain sufficient and necessary conditions for the existence, invertibility and square summability of kernels $\tau (\mathbf{s}; d), \mathmb{s} \in \mathbb{Z}^{\nu}$ of $(I-T)^d $. Asymptotic behavior of $\tau (\mathbf{s}; d)$ as $|\mathbf{s}| \to \infty$ is identified following local limit theorem for random walk. A class of fractionally integrated random fields $X$ on $\mathbb{Z}^{\nu}$ solving the difference equation $(I-T)^d X = \varepsilon$ with white noise on the right-hand side is discussed, and their scaling limits. Several examples including fractional lattice Laplace and heat operators are studied in detail.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Academics in healthcare grapple with the challenge of efficiently managing time while addressing diverse roles and responsibilities, leading to heightened levels of anxiety and stress within the academic community. The primary objective of this study is to offer a sustainable and systemic solution to the prevalent time-management challenges in healthcare academia, through the development of a predictive model. Employing systemic analysis software and adopting a systemic management approach, we crafted a model to address academic time-management concerns. The dynamics of time allocation for academicians are governed by three fundamental pillars: teaching, research, and administrative tasks. Significantly prioritizing administrative tasks depletes valuable academic time, making time management within academia excessively costly. This occurs as highly skilled individuals find themselves diverted towards administrative duties at the expense of their academic roles diminishing resilience levels. The proposed Timebooster Academic Systemic Model (TASM) advocates for the cultivation of soft skills in academia, en-compassing prioritization, seeking assistance, and addressing tendencies of perfectionism and procrastination. Additionally, TASM recommends the implementation of full automation, delegation of administrative responsibilities, and the mitigation of both overt and covert time-consuming elements. Furthermore, TASM reports on the pivotal role of the academic resilient manager-leaders, who actively contribute to their own satisfaction and academic growth by enhancing collaboration and teamwork. Time-management challenges emerge as a critical determinant of academic well-being and resilience. Systemic models, exemplified by TASM, offer a valuable framework for investigating prioritization concerns, identifying administrative impediments in academic processes, and managing low-value time-consuming elements. The TASM model, along with the systemic philosophy underpinning its design, presents an avenue for advancing the exploration of time-management phenomena within the context of healthcare academia.

There are rich proper noun derivative semantic relationships in geographic entity vector data. The identification of traditional proper noun derivative semantic relationships usually requires toponym researchers to examine the source of derived toponyms by consulting a large number of toponym documents. This method cannot adapt to the mining of proper noun derivative semantic relationships for large-scale geographical entity. In this regard, this paper proposes a method of identifying the proper noun derivative semantic relationships for geographical entity by combining prompt learning and XGBoost model. This method transforms the extraction problem of proper noun derivative semantic relationships into a binary classification problem by analyzing the characteristics of the derivation relationship of toponyms in the form of toponyms and the spatial and temporal distribution of geography. Firstly, prompt learning and gaussian mixture model are used to extract and cluster the derivation words of toponyms, so as to realize the recognition of derived toponyms collections. Then, enumerate the possible proper noun derivations in the toponym set, and then the XGBoost model is used to identify the semantic relations derived from the proper noun of geographical entities. In the experiment, the recognition method of proper noun derivative semantic relationships based on prompt learning and XGBoost proposed in this paper has achieved good relationship recognition effect in the experiment. This method has certain practical value in the fields of toponym management and toponym translation.

The physical roots, interpretation, controversies and precise meaning of the Landauer Principle are surveyed. Landauer's principle is a physical principle pertaining to the lower theoretical limit of energy consumption of computation. It states that an irreversible change in information stored in a computer, such as merging two computational paths, dissipates a minimum amount of heat kBTln2 per a bit of information to its surrounding. The Landauer Principle is discussed in the context of fundamental physical limiting principles, such as the Abbe diffraction limit, the Margolus-Levitin limit and the Bekenstein limit. Synthesis of the Landauer bound with the Abbe, Margolus-Levitin limit and Bekenstein limits yields the minimal time of computation, which scales as τmin~hkBT. Decrease in a temperature of a thermal bath will decrease the energy consumption of a single computation, but, in parallel, it will slow the computation. The Landauer principle bridges between John Archibald Wheeler “it from bit” paradigm and thermodynamics. Experimental verifications of the Landauer Principle are surveyed. Interrelation between thermodynamic and logical irreversibility is addressed. Generalization of the Landauer principle to the quantum and non-equilibrium systems is addressed. Landauer Principle represents the powerful heuristic principle bridging the physics, information theory and computer engineering.

This study delves into the critical domain of public procurement, specifically focusing on Sustainable Public Procurement (SPP) and Environmental, Social, and Governance (ESG) considerations within the context of South Korea. The aim of this research is to empirically scrutinize the factors influencing the impact index of SPP, with a particular emphasis on services related to labor standards. The investigation spans three years, from January 1, 2019, to July 31, 2021, encompassing state agency orders and post-implementation legal changes. Leveraging the comprehensive Korea On-line E-Procurement Sys-tem(KONEPS) platform, we meticulously collected data, ultimately culminating in 21,573 services meeting our criteria, from which 250 cases underwent an in-depth analysis. The study sheds light on the influence of social responsibility evaluation cri-teria on overall procurement scores, while also uncovering the moderating effects of various factors. The outcomes of this study offer valuable insights into the impact index of social responsibility evaluation criteria within South Korea's public procurement landscape. Factors including procurement year, classification, service period, and estimated price were identified as significant influencers. Moreover, the number and location of evalu-ation criteria items, inclusion of sincerity elements, and the evaluating agency were deemed pivotal determinants of the influence index. These findings hold profound implications for policymakers, procurement practitioners, and researchers and provide a roadmap for optimizing the utilization of social responsibility evaluation criteria to advance responsible and sustainable procurement practices. Future research avenues include conducting further study of additional moderat-ing variables, expanding datasets to encompass a broader spectrum of procurement contexts, and evaluating the long-term repercussions of social responsibility evaluation on procurement outcomes. These endeavors promise to further refine and advance public procurement practices in South Korea and beyond.

Developing sustainability competences is an important endeavor for education, as competence development can be complex and requires appropriate approaches. In the case of preparing future educators, this becomes even more important, because of their multiplier role. The current study presents how a project, based on living-lab methodology, helped preservice preschool teachers, attending a course on sustainability issues, develop sustainability-specific professional action competence. Students collaborated with an organization and a school and were trained to deliver to 6-year-old pupils, activities concerning the protection of sea turtles. The process included reflection, based on a given template. After the intervention, the preservice preschool teachers reflected upon their role and professional performance and discussed how they, benefited from this project. They further analyzed through a group interview, how the Living Lab methodology raised their professional confidence and self-efficacy, and helped them develop content knowledge, pedagogical content knowledge, and a sense of purpose and motivation for teaching about sustainability. Outcomes indicate that participants felt confident and efficacious to teach about sustainability, and developed their content knowledge, pedagogy content knowledge, motivation, and volition due to a strong sense of purpose and responsibility. The overall process facilitated the development of critical thinking, systemic thinking, reflection, and collaboration..

This study introduces SkinLiTE, a lightweight supervised contrastive learning model, tailored to enhance the detection and typification of skin lesions in dermoscopic images. The core of SkinLiTE lies in its unique integration of supervised and contrastive learning approaches, which leverages labeled data to learn generalizable representations. This approach is particularly adept at handling the complexities and imbalances inherent in skin lesions datasets. The methodology encompasses a two-phase learning process. In the first phase, SkinLiTE utilizes an encoder network and a projection head to transform and project dermoscopic images into a feature space where contrastive loss is applied, focusing on minimizing intra-class variations while maximizing inter-class differences. The second phase freezes the encoder's weights, leveraging the learned representations for classification through a series of dense and dropout layers. The model was evaluated using three datasets from Skin Cancer ISIC 2019-2020, covering a wide range of skin conditions. SkinLiTE demonstrated superior performance across various metrics—accuracy, AUC , and F1 score—particularly when compared with traditional supervised learning models. Notably, SkinLiTE achieved an accuracy of 0.9087 using AugMix augmentation for binary classification of skin lesions. It also showed comparable results with the state-of-the-art approaches of ISIC challenge without relying on external data, underscoring its efficacy and efficiency. The results highlight the potential of SkinLiTE as a significant step forward in the field of dermatological AI, offering a robust, efficient, and accurate tool for skin lesion detection and classification. Its lightweight architecture and ability to handle imbalanced datasets make it particularly suited for integration into Internet of Medical Things environments, paving the way for enhanced remote patient monitoring and diagnostic capabilities. This research contributes to the evolving landscape of AI in healthcare, demonstrating the impact of innovative learning methodologies in medical image analysis.

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

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

The objective of this research is to establish a better understanding of the current landscape of digital learning research and sustainable development by using CiteSpace. First, we retrieved published publications from the Web of Science (2004–2022). Following that, we examined the primary research strengths and important subjects of digital learning from two perspectives: collaboration networks (including collaborative networks across countries, institutions, and authors) and co-citation networks. We examined the co-citation network from three perspectives: cluster analysis, the most active citers, top references. Furthermore, referenced journals, popular themes, and rising trends were examined. These findings indicate the primary study subjects in the field of digital learning, the most intriguing research literature, and each period's emerging research hotspots. Finally, we proposed further study ideas for future paths.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

.With the increasing use of carbon fiber reinforced plastics in various area, carbon fiber composites based on prepregs have attracted attention in industries and academia research. However, prepreg manufacturing processes are costly, and the strength of structures varies depending on the orientation and defects (pores and delamination). For non-contact evaluation of internal defects, we proposed lock-in infrared thermography to investigate orientation angles after a compression test. We also conducted a drop-weight impact test to study the behaviour of the composites after impact according the fibers orientation for composite fabricated using unidirectional carbon fiber prepregs. Using CAI tests, we determined the residual compressive strength and confirmed the damage modes using a thermal camera. The results of the drop weight impact tests show that the specimen laminated at 0° suffered the largest damage because of susceptibility of the resin to impact. In contrast, the specimens oriented in of 0°/90° and +45°/–45° directions transferred more than 90% of the impact energy back to the impactor because of the lamination of fibers in the orthogonal directions. Furthermore, the specimens that underwent complete damage in the impact tests were subjected to the lock-in method and showed internal delamination and cut fibers. With the finite elements analysis, the damage of each ply could be observed. Moreover, the temperature differences in the residual compression tests were not significant.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Infrared thermography has already been proven to be a significant method in non-destructive evaluation since it gives information with immediacy, rapidity and low cost. However, the thorniest issue for wider application of IRT is the quantification. In this work, we proposed a specific depth quantifying technique by employing the Gated Recurrent Units (GRU) in composite material samples via pulsed thermography (PT). Carbon Fiber Reinforced Polymer(CFRP) embedded with flat bottom holes were designed via Finite Element Method (FEM) modeling in order to precisely control the depth and geometrics of the defects. The GRU model automatically quantified the depth of defects presented in the CFRP material. The proposed method evaluated the accuracy and performance of synthetic CFRP data from FEM for defect depth predictions.

In the quest for more sustainable urban landscape development, the concept of ‘green infrastructure’ (GI) has become central in policy documents and as a multifunctional general planning tool. GI is not however a simple and unambiguous solution. While there in policy documents are claims for more and connected GI, actual urban development takes another direction. The densifying imperative is hard to combine with an increased and more connected GI. This paper argues for a critical and diversified approach to the concept of GI, to facilitate its implementation in urban planning and management. While GI most often is seen as a common asset and a public good, the actual land use negotiations and management responsibilities cannot be limited to a public service discourse, but should address more clearly a variety of actors. Linguistic as well as spatial definitions of the two relevant dichotomies of ‘green-grey’ and ‘public-private’ are crucial in GI location, design, construction and management, it is argued. Overarching representations of GI will be needed, but also – and linked to it – a spatial storm water plan and an overall plan for public space. The development over time will need an intersectorial implementation and management program. Thus some of the GI intentions may be implemented in planning processes, some through reorganisation and redesign of public space, and some by agreements with landowners.

Motivated by a common Mathematical Finance topic, this paper surveys several results concerning windings of 2-dimensional processes, including planar Brownian motion, complex-valued Ornstein-Uhlenbeck processes and planar stable processes. In particular, we present Spitzer's asymptotic Theorem for each case. We also relate this study to the pricing of Asian options.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Chronic Hepatitis B Virus (HBV) infection remains a significant public health concern, particularly in Africa, where the burden is substantial. HBV is an enveloped virus, classified into ten phylogenetically distinct genotypes (A – J). Tests to determine HBV genotypes are based on full-genome sequencing or reverse hybridization. In practice, both approaches have limitations. Whereas diagnostic sequencing, generally using the Sanger approach, tends to focus only on the S-gene and yields little or no information on intra-patient HBV genetic diversity, reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV diagnostic sequencing protocol suitable for clinical virology that yields both complete genome sequences and extensive intra-patient HBV diversity data. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit, ONT GridION sequencing, genotyping using Genome Detective software, recombination analysis using jpHMM and RDP5 software, and drug resistance profiling using Geno2pheno software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 residual diagnostic samples from HBV-infected patients in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world.

Background/Objectives: Distance or urbanisation settings may affect active commuting to school (ACS). This study aimed to (i) detect home-school threshold distances of walking to school and (ii) predict walkable distances among adolescents in different urbanisation settings and both sexes, and (iii) to identify variables predicting adolescents’ ACS, in a central Spain region. Methods: The PACOyPACA (Spanish acronym for Pedal-and-Walk to School, Pedal-and-Walk Home) study evaluated adolescents attending urban, semi-urban and rural schools from Castilla-La Mancha region. The sample included 448 adolescents [48.9% females, mean age 14.80 (SD=0.60)] living closer than 5,100m from school. Distance was divided into deciles to detect which adolescents walked more. Most walkable distances within the whole sample, by sex and by urbanisation settings were predicted using Receiver Operating Characteristic (ROC) curves. Variables affecting ACS were found with binary logistic regression. Significance was set at p≤0.05. Results: Most adolescents walked to school (73.1%). Commuting modes differed significantly by urbanisation settings (p=0.001), but not by sex. Most walked when living around 1,400m from school or closer within the whole sample, in both sexes and in urban and semi-urban settings, and adolescents within rural settings did it until 750-900m. Walkable distances were 1,350m for the whole sample and both sexes, and 1,450, 1,350 and 800 within urban, semi-urban and rural settings, respectively. Distance was the only predictor of ACS (p<0.001). Conclusions: Walkable home-school distances differed based on urbanisation settings, which may be due to the classification of urbanisation settings. This study addresses schools within scarcely populated areas.

Primary themes in intergenerational justice are a healthy environment, the perpetuation of Earth’s biodiversity, and the sustainable management of the biosphere. However, the current rate of species declines globally, ecosystem collapses driven by accelerating and catastrophic global heating and a plethora of other threats, preclude the ability of habitat protection alone to prevent a cascade of amphibian and other species mass extinctions. Reproduction biotechnologies, biobanking, and conservation breeding programs (RBCs), enabling species restoration, offer a critical transformative change that can economically and reliably perpetuate species irrespective of environmental targets. These capacities extend indefinitely into the future and satisfy humanities needs as the biosphere expands into space. Currently applied RBCs include the hormonal stimulation of reproduction, the collection and refrigerated storage of sperm and oocytes, sperm cryopreservation, in vitro fertilisation, along biobanking. Advanced biotechnologies such as assisted evolution and cloning for species adaptation or restoration have yet to be fully realised. We broaden our discussion to include genetic management, broad political and cultural engagement, and future applications. The development and application of RBCs, and particularly assisted evolution and species restoration, raise intriguing ethical, theological, and philosophical issues. We address these themes with amphibian models to introduce the MDPI Special Issue, The Sixth Mass Extinction and Species Sustainability through Reproduction Biotechnologies, Biobanking, and Conservation Breeding Programs.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

Objective: To analyse the association between maternal risk factors such as age, body mass index (BMI) and cigarette smoking, with perinatal outcomes. Materials and Methods: This a retrospective analysis from prospectively collected data performed at Hospital Universitario de Torrejón (Madrid, Spain), between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. Association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small for gestational age (SGA) or fetal growth restricted (FGR) neonates and type of delivery according to maternal age, BMI, and cigarrete smoking was studied. Logistic mixed models were used to analyze the data. Results: 1921 patients were included in the analysis. Women of 40 years old had a significantly higher risk of having GDM (Odds Ratio (OR) 1.61, 95% Confidence Interval (CI) 1.08 to 2.36), and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI <18 had an increased rate of birth SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). A targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented an expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Cationic Antimicrobial Peptides (AMPs), also called Host Defence Peptides have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but remains relatively less explored in the generation of anticancer candidates. Herein, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, have been conjugated to L-K6, a lysine/leucine rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from, overall, reduction of the activity from the parent drugs to their conservation or even enhancement. Notably, the conjugates retain some anti-TDP1 activity and display intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Sarcoglycanopathies are among the most frequent and severe autosomal recessive forms of limb-girdle muscular dystrophies /LGMD/ with childhood onset. Mutations in , , and sarcoglycan genes lead to various kinds of LGMD. We present the clinical variability of LGMD 2C/R5 among a genetically homogeneous group of 56 patients, belonging to 35 pedigrees. Molecular genetic analysis showed thаt all 57 patients were homozygous for C283Y variant. The muscles of the pelvic girdle and the trunk were early and more severely affected, followed by the the shoulder girdle. Macroglossia, hypertrophy of the calves, scapular winging and lumbar hyperlordosis were common in the ambulatory phase. A great variability in the clinical presentation of LGMD 2C/R5 was observed both intra and interfamilial, despite the same underlying molecular defect. Females demonstrated a relatively milder clinical course, compared to males. Mean CK levels were 20 times above normal values. Muscle CT of MRI showed earlier and more severe involvement of the flexor proximal limb muscles in comparison to the extensor ones.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

In the pursuit of functional foods that promote health, nanoliposomal carriers have been used to enhance the stability and functionality of dairy products such as yogurt, promising therapeutic benefits. This study aimed to evaluate the impact of fucoxanthin-loaded nanoliposomes in yogurt on its antioxidant, physico-chemical, and rheological properties under cold storage (21 days). Fucoxanthin-loaded nanoliposomes were prepared using the ultrasonic film dispersion technique and added at concentrations of 0%, 5% and 10% at the yogurt (Y-C, Y-FXN-5, Y-FXN-10). Homogeneous and uniform nanoliposomes (98.28 nm) were ob-tained, preserving their integrity and functionality, and ensuring prolonged release and bioavailability of fucoxanthin. Y-FXN-10 maintained the highest antioxidant activity according to the DPPH (52.96%), ABTS (97.97%), and FRAP (3.16 mmol ET/g) methods. This formulation exhibited enhanced erythroprotective potential, inhibiting hemolysis, photohemolysis, and heat-induced hemolysis, thereby preventing lipid pe-roxidation. However, viscosity and firmness decreased, affecting the texture and appearance. Sensory properties such as color, flavor, aftertaste, texture, and overall acceptance improved with the 10% fuco-xanthin-enriched yogurt formulation. These results suggest that nanoliposomal are suitable for carries fuco-xanthin, their incorporation into food matrices is key to developing functional foods. Regulatory approvals and consumer perceptions regarding nanotechnology-based products must be addressed, emphasizing their safety and health benefits.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

The mystery phenomenon of fungal bioluminescence has always captivated human curiosity, although more attempts need to be made, particularly to bring the new species to the surface. In this study, we devoted considerable space to the taxonomy of these fungi while discussing their biogeography, evolution, bioluminescence mechanism, and potential ecological roles. We provide a detailed explanation of how these fungi produce light, including the role of the enzyme luciferase and luciferin. We also discussed their applications. Here, we presented an updated list of 122 bioluminescent fungi identified from five distinct evolutionary lineages viz. Armillaria, Eoscyphella, Lucentipes, Mycenoid, and Omphalotus worldwide, mainly in tropical and subtropical areas. The bioluminescent fungi descended from the last common ancestor of the mycenoid and the marasmioid clades of Agaricales, which have been maintained for at least 160 million years of evolution. We highlighted the need for further research to understand the ecological role of bioluminescent fungi. Applying bioluminescent fungi in various areas (e.g., environmental and medicinal) demonstrates their validity.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective for ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions.

Limited evidence on hepatitis A seroprevalence among HIV-exposed uninfected (HEU) children compared to their HIV infected (HIV) and unexposed uninfected (HUU) counterparts compromises rational vaccine decision-making. This study comprised of a retrospective health facility-based population of children aged 1 month – 12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on HIV exposure or infection status. Of 513 participants, 54% (277) were male and the median age was 10 (IQR: 4 – 25) months. The median maternal age was 29 (IQR: 25 – 34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2-98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1-25.7]), while 1.1% (2/188 [95% CI 0.12-2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV=60%, 6/10 [95% CI 27.4-86.3] and HEU=45%, 9/20 [95% CI 23.8-68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4-37.0]). Natural immunity among HIV -exposed and -unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood.

The global aging population has experienced rapid growth in recent decades, leading to an increased prevalence of psychiatric disorders, particularly depression, among older adults. Depression in the elderly is often compounded by chronic physical conditions and various psychosocial factors, significantly impacting their quality of life. This paper explores the epidemiology of geriatric depression, highlighting the influence of gender, race, and socio-economic status on its prevalence. The classification and diagnosis of geriatric depressive disorders, based on ICD-11 and DSM-5 criteria, reveal the complexity of managing these conditions in older adults. Personalized Medicine (PM) emerges as a promising approach, focusing on tailoring treatments to the individual’s genetic, clinical, and environmental characteristics. However, the application of PM in this demographic faces challenges, particularly in the context of pharmaceutical forms. The need for age-appropriate drug delivery systems is critical, given the prevalence of polypharmacy and issues such as dysphagia among the elderly. This study emphasizes the importance of developing patient-centric formulations to enhance the effectiveness of personalized therapy in geriatric patients.

Salmonella species are important foodborne pathogens worldwide. Salmonella pathogenicity is associated with multiple virulence factors and enhanced antimicrobial resistance. To determine the molecular characteristics and genetic correlations of Salmonella, 24 strains of Salmonella isolated from different sources (raw poultry, human stool, and food) in the Wenzhou area were investigated to determine the distribution of antimicrobial resistance and virulence determinants using whole-genome sequencing (WGS). Aminoglycoside-resistance genes were detected in all samples. Over half of the samples found antimicrobial resistance genes (ARGs) and point mutations for several clinically frequently used antibiotic, β-lactamases, tetracyclines, and fluoroquinolones. Of these strains, 62.5% were predicted to be multidrug-resistant (MDR). The quinolone-modifying enzyme gene aac(6')-Ib-cr, detected in five samples (S1–S4 and S10), were located on integrons. Analysis of Salmonella pathogenicity island (SPI) profiles suggests that serotypes with close genetic relationships share the same distribution of virulence factors, revealing a link between genotype and SPI profiles. CgMLST analysis indicated that five isolates S14–S18 were closely related to strains originating from the UK, suggesting that they may have been introduced from the UK. Data from this study may enrich the molecular traceability database for Salmonella and provide a basis for effective public health policies.

Clathrate hydrate-based technologies have been considered as promising and sustainable alternatives for the effective management of the climate change risks related to emissions of carbon dioxide, produced by human activities. This work presents a combined experimental and computational investigation of the effects of the operational procedures and characteristics of the experimental configuration, on the phase diagrams of CO2-H2O systems and CO2 hydrates formation, growth and dissociation conditions. The operational modes involved (i) the incremental (step-wise) temperature cycling and (ii) the continuous temperature cycling processes, in the framework of an isochoric pressure search method. Also, two different high pressure PVT configurations were used, of which one encompassed a stirred tank reactor and the other incorporated an autoclave of constant volume with magnetic agitation. The experimental results implied a dependence of the subcooling, (P, T) conditions for hydrate formation and dissociation and thermal stability of the hydrate phase on the applied temperature cycling mode, and the technical features of the utilized PVT configuration. The experimental findings were complemented by a thermodynamic simulation model and other calculation approaches, with the aim to resolve the phase diagrams including the CO2 dissolution over the entire range of the applied (P, T) conditions.

Due to global climate change, cold temperatures have significantly impacted rice production, resulting in reduced yield and quality. In this study, we investigated two traits related to cold tolerance (CT) of 1992 diverse rice accessions at the seedling stage. Geng accessions exhibited higher levels of CT compared to xian accessions, with the GJ-tmp subgroup displaying the strongest CT. However, extreme CT accessions were also identified within the xian subspecies. Through GWAS analysis based on survival rate (SR) and leaf score of cold tolerance (SCT), a total of 30 QTLs associated with CT at the seedling stage were identified, among which four QTLs (qSR3.1a, qSR4.1a, qSR11.1x and qSR12.1a) were found to be important. Furthermore, five candidate genes (LOC_Os03g44760, LOC_Os04g06900, LOC_Os04g07260, LOC_Os11g40610 and LOC_Os12g10710) along with their favorable haplotypes were identified through gene function annotation and haplotype analysis. Pyramiding multiple favorable haplotypes resulted in a significant improvement in CT performance. Subsequently, three selected accessions (CX534, B236, and IRIS_313-8565), carrying different superior alleles for CT, were selected and recommended for molecular breeding for CT using marker-assisted selection (MAS). The findings from this study provide valuable resources for enhancing rice's ability for CT while laying a foundation for future cloning of novel genes involved in conferring CT.

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in laboratory small animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homologue of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells or replication in primary neuronal cells. In western blots of EHV-1-infected cell lysates, an EHV-1 Us9-specific polyclonal antibody detected multiple bands ranging from 35 to 42-kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76 and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that the ORF76 (US9) plays an essential role in the anterograde spread EHV-1.

Increasing awareness of the potential health risks associated with microplastics (MPs) presence in the environment has led to significant rise in research focused on these particles over the past few years. This review focuses on research on MPs presence and spread, pathways of exposure and toxicological effects on human health and legal framework related to MP challenges. Several research projects have aimed to assess their potential harm to human health. Toxicological effects have been noticed at high concentrations of MPs, specifically polystyrene, the most widespread typical MP, but only short-term effects have been mostly studied. Significant quantities of consumed MP have been discovered to have diverse detrimental effects, posing a threat to human welfare. The exact concentrations of microplastics that are inhaled and swallowed and then build up in the human body are still not known. Further investigation is necessary to evaluate the impact of MP contamination at minimal concentrations and for prolonged durations.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

Groundwater flow and transport models are essential tools for assessing and quantifying the mi-gration of organic contaminants at polluted sites. Uncertainties in the hydrodynamic and transport parameters of the aquifer have a significant effect on model predictions. Uncertainties can be quantified with advanced sensitivity methods such as Sobol’s High Dimensional Model Reduction (HDMR) and Variogram Analysis of Response Surfaces (VARS). Here we present the application of VARS and HDMR to assess the global sensitivities of the outputs of a transient groundwater flow model of the Gállego alluvial aquifer which is located downstream the Sardas landfill in Huesca (Spain). The aquifer is subject to the tidal effects caused by the daily oscillations of the water level in the Sabiñánigo reservoir. Global sensitivities are analysed for hydraulic heads, aquifer/reservoir fluxes, groundwater Darcy velocity and hydraulic head calibration metrics. Input parameters in-clude aquifer hydraulic conductivities and specific storage, aquitard vertical hydraulic conductiv-ities, and boundary inflows and conductances. VARS, HDMR and graphical methods agree to identify the most influential parameters which for most of the outputs are the hydraulic conduc-tivities of the zones closest to the landfill, the vertical hydraulic conductivity of the most permeable zones of the aquitard, and the boundary inflow coming from the landfill. The sensitivity of heads and aquifer/reservoir fluxes with respect to specific storage change with time. The aquifer/reservoir flux when the reservoir level is high shows interactions between specific storage and aquitard conductivity. VARS and HDMR parameter rankings are similar for the most influential parameters. However, there are discrepancies for the less relevant parameters. The efficiency of VARS was demonstrated by achieving stable results with a relatively small number of simulations.

Considering animal welfare, the free-range laying hen farming model is increasingly gaining attention. However, in some countries, large-scale farming still relies on the cage-rearing model, making the focus on the welfare of caged laying hens equally important. To evaluate the health status of caged laying hens, a dataset comprising visible light and thermal infrared images was established for analyses, including morphological, thermographic, comb, and behavioural as-sessments, enabling a comprehensive evaluation of the hens' health, behaviour, and population counts. To address the issue of insufficient data samples in the health detection process for indi-vidual and group hens, a dataset named BClayinghens was constructed containing 61,133 images of visible light and thermal infrared images. The BClayinghens dataset was completed using three types of devices: smartphones, visible light cameras, and infrared thermal cameras. All thermal infrared images correspond to visible light images and have achieved positional alignment through coordinate correction. Additionally, the visible light images were annotated with chicken head labels, obtaining 63,693 chicken head labels, which can be directly used for training deep learning models for chicken head object detection and combined with corresponding thermal infrared data to analyze the temperature of the chicken heads. To enable the constructed deep-learning object detection and recognition models to adapt to different breeding environ-ments, various data enhancement methods such as rotation, shearing, colour enhancement, and noise addition were used for image processing. The BClayinghens dataset is important for ap-plying visible light images and corresponding thermal infrared images in the health detection, behavioural analysis, and counting of caged laying hens under large-scale farming.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

Background: Medication errors often stem from incomplete or incorrect transfer of drug information during reviews. To enhance medication review processes, a collaborative healthcare team, including a pharmacist in the surgical ward, is essential. This study aimed to identify the frequency and the kind of intentional and unintentional discrepancies related to the prescriptions within two surgical wards. Methods: A prospective observational study was conducted among adult patients admitted to two surgical settings. The patients were selected between May 30th and November 30th, 2021. The study followed a three-phase structure: patient selection, medication review to identify discrepancies and DRPs, and the detection of any such issues in the discharge letter. Results: The most frequent types of discrepancies collected were substitutions (60.9%) for the Endocrinological Surgery and omissions for General Surgery (53.4%). In Endocrinological Surgery, 45.9% of cases exhibited class C drug interactions. In General Surgery, class D drug interactions were predominantly observed (54.1%), with 93.3% attributed to drugs carrying an elevated risk of prolonging the QT interval. Conclusions: Frequently, the medication review process is superficially carried out, introducing errors that may adversely affect patient health. This study explores the potential positive impact of involving the clinical pharmacist in identifying and managing discrepancies and DRPs.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

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

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

The objective of this paper was to study the expression pattern of the GLOD4 gene in the testis and its regulatory effect on testicular cells. Currently, the regulated mechanism through are unclear. Here, we explored how GLOD4 functions in goat leydig cells to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated that the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in 4 age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT‒PCR) and protein blotting. Finally, we performed GLOD4 gene silencing and overexpression studies in testicular cells from goats and explored the effects of GLOD4 on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in testicular leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD and CYP17A1 and the mRNA expression levels of cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases,promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, Proliferation and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in the cells of goats.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Background: The study was conducted to investigate if the mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). The lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating delivery into cells. However, its utility at the temperature and specific biological environment in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated by in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated by immunohistochemistry. EGFP was observed in cells infiltrating the space between the muscle cells in a focal inflammatory response. Conclusion: The results indicate that the N1-methyl-pseudouridine modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

In this study, the mechanical and piezoresistive properties of mortars reinforced with carbon nanotubes (CNTs) and carbon micro fibers (CMFs) are determined. Silica fume as well as a polymer with polyalkylene glycol graft chains were used as dispersant agents for the CNTs and CMFs incorporation into the cement paste. The mechanical properties of the mortar composites were investigated in respect to their flexural and compressive strength. A four-probe method was used for the estimation of their piezoresistive response. The test outcomes revealed that the combination of the dispersant agents along with a low content of CNTs and CMF by weight of cement (bwoc) result in the production of a stronger mortar with enhanced mechanical performance and durability. More specifically, there was an increase in flexural and compressive strength up to 38% and 88%, respectively. Moreover, the piezoresistive response of the reinforced cementitious materials was attributed to the variation of electrical resistivity due to tunneling transport of electrons stemming from two different mechanisms due to the incorporation of the conductive admixtures (CNTs and CMF). This work aims to contribute to the progress acceleration in the field of developing structural materials with self-sensing and electrical actuation related properties.

Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS). Multiple noninvasive respiratory support modes are currently available in Romania, but little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). We aimed to identify the usage extent and clinical application of nHFOV in Romania. A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. The questionnaire was addressed to the leaders of all level III Romanian NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU’s size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10-17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%), heated, humidified high flow nasal cannula (HHHFNC) (61.9%), and nHFOV (11/21 units; 52.4%); 5/11 units reported frequent nHFOV use (in 2 or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). 10/11 units reported setting a mean airway pressure (MAP) equal to the CPAP level plus 1-2 cmH₂O on rescue nHFOV after CPAP failure. Both dedicated equipment (45.5%) and hybrid ventilators (63.6%) were used for nHFOV delivery, with face/nasal masks and short binasal prongs being the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV; none of the units mentioned pneumothorax as an adverse effect. Only 3 of the NICUs had a written protocol for nHFOV use. Initial, minimum, and maximum amplitude and initial and minimum MAP settings used were significantly higher with hybrid ventilators as compared to dedicated equipment (p<0.05). Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV. A need for training for nHFOV use was identified, and efforts are needed at the national level to develop courses and training sessions, including using simulation workshops, to offer more information on optimal nHFOV use in clinical practice.

(1) Background: This study aims to investigate differences in the perspectives of exercise intensity for resistance exercise of healthcare professionals (HCPs) and adults living with spinal cord injury (SCI) in Asian countries. Also, it verifies the appropriateness of the conventional indicators for resistance exercise intensity in an Asian context; (2) Methods: 121 certified HCPs and 107 adults with SCI participated in a survey conducted in Indonesian, Japanese, Korean and Thai languages. The survey asked what principles are important for prescribing resistance exercise, and if ‘moderate’ and ‘vigorous’ were appropriate terms for indicating an intensity level. Perspective differences were examined between both groups and, further, between countries from a psychosocial perspective; (3) Results: Of the HCPs, 92% perceived that resistance exercise intensity was far more important than frequency, time or type of exercise while frequency (61%) followed by intensity (58%) was perceived as important by respondents with SCI. Only Japanese respondents with SCI agreed with HCP’s perception of intensity. Both HCPs and respondents with SCI showed unfavorable responses on the usage of ‘moderate’ and ‘vigorous’ for describing resistance exercise intensity, especially Japanese HCP and respondents with SCI from Indonesia; (4) Conclusion: Our findings suggest that non-HCPs must improve their perceptions of exercise intensity. Findings also suggest the need for more explicit and user-friendly terms or expressions indicating the level of intensity in a local (Asian) context.

This study investigated the content of macro- and microelements in the lower reaches of the Ob River (Western Siberia). Seasonal sampling was performed over a four-year period (2020-2023) during the main hydrological seasons (winter low water, spring-summer floods, and early fall low water) at three river stations. Suspended and dissolved fractions were separated by filtration through 0.45-micron nitrocellulose filters. The results revealed significant seasonal variations in the elemental content of the Ob River water, associated with changes in catchment inputs, physical and chemical conditions of the aquatic environment, and the amount and composition of incoming suspended sediment. During high water flow events in the Ob River, the concentration of suspended solids increased substantially. These included significant quantities of sparingly soluble hydrolysates such as Al, Ti, Zr, Ga. During the winter period when the Ob River was ice-covered, a 2- to 3-fold rise was observed in the concentration of Na, Mg, Ca, K, Si, Mn. Having accounted for these seasonal variations in water chemistry, we were able to refine our estimates of elemental export to the Arctic Ocean. Compared to estimates from previous studies, we observed with 2.3-fold higher dissolved loads of Mn, 2.1-fold for Zn, 1.6-fold for Fe, and 1.4-fold for Pb.

The Lower Mekong Basin has had extensive hydropower dam development, which changes hydrologic conditions and threatens the exceptional aquatic biodiver-sity. This study quantifies the degree of hydrologic change between pre-impact (1965-1968) and post-impact (2018-2021) peak hydropower development in two major tributaries of the Lower Mekong Basin, the Sekong River with the fewest dams and the Sesan River with the most dams. Both rivers historically supported migratory fishes. We use daily pre- and post-impact data and the Indicators of Hydrologic Alteration framework to evaluate streamflow changes from dam development. We found signifi-cant changes in low and high magnitude flows in the pre- and post-impact periods of dam development. For the Sekong River, minimum flow had large fluctuations that ranged 290% to 412% more than the pre-impact period, while the Sesan River ranged 120% to 160% more than pre-impact. Dry season flows increased by 200±63% on av-erage in the Sekong River, which is caused by releases from upstream dams. Mean-while, Sesan River dry season flows increased by 100±55% on average. This study in-dicates that seasonal flow changes and extreme flow events occurred more frequently in the two basins following dam construction, which may threaten the ecosystem func-tions.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

Pig farms management is involved in multiple factors such as environmental conditions, animal behavior, weight gaining and others. In all those scenarios, it is fundamental to detect each individual and its development as it grows to reach the shipment phase. Therefore, the objective of this study was to apply an automatic individual pig detection algorithm using Deep Learning Techniques, in frames taken from videos recorded during the weaning phase in real production conditions of small and medium producers in tropical conditions in Colombia. The weaning phase was selected because individual detection in each cage is more difficult due to environmental adaptations that piglets undergo after nursing. Piglets tend to cluster together during this phase, making image processing more challenging compared to the fattening phase, where animals are more isolated. The You Only Look Once (YOLOv7) algorithm and VGG Image Annotator were used to detect individuals in two pens separated by gender. All animal postures, lighting conditions were considered. The Precision, Recall and mAP metrics were used to assess the model performance with different confidence values. A precision of 98.3% in a threshold of 0.9 was reached, Recall of 98.5% in a threshold of 0.85. Data augmentation techniques were important to increase the dataset and to have a more realistic model for individuals’ detection. The method used allowed us to identify all the complete pigs’ bodies under different posture and lighting situations.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

This aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in 73 men with and without insulin resistance. The participants were divided based on insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and the duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. The results highlighted associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of insulin resistance was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. The study underscores the negative impact of modern civilization’s lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. The study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of insulin resistance.

This study compared the efficacy of alfaxalone and propofol to induce anesthesia in bitches undergoing an ovariohysterectomy or cesarean sections. 34 healthy and pyometra-affected females were induced with IV propofol administration, 35 healthy and pyometra-affected bitches were induced with the IV administration of alfaxalone. For the cesarean sections, females were induced with propofol (n=14) or alfaxalone (n=14). Maternal physiological parameters (heart rate, blood pressure, temperature) were recorded throughout surgeries; the viability and a modified Apgar score was recorded in the neonates at 5, 60 and 120 minutes after delivery. The use of propofol and alfaxalone did not show relevant differences over parameters assessed, when ovariohysterectomy was performed in healthy bitches or females with pyometra, as well as when cesarean sections were compared; only, a transient tachycardia appeared after alfaxalone administration. However, a higher percentage of bitches needed extra-doses of propofol. Neonatal mortality was similar between both groups, but when alfaxalone was used a higher neonatal viability was observed. Propofol and alfaxalone showed similar efficacy to perform the ovariohysterectomy in all bitches. Both protocols were optimal for cesarean sections, but alfaxalone was associated with a higher neonatal viability and a higher neonatal survival rate.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of vaccination declines experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on impacts to routine childhood vaccinations in low-income countries from January 1, 2020 to February 8, 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

The aim of this study is to characterize the compound extremes of rainfall and temperature in Côte d’Ivoire. For this purpose, we analyzed the outputs of fourteen (14) climate models from the CORDEX-Africa project. Results show an increase (approximately 4.3°C) of the surface temperature and a decrease (5,90 %) of the mean rainfall in the near (2036-2065) and far futures (2071-2100) over Côte d’Ivoire during January-February-March (JFM) period. The analysis of the compound extremes of wet/warm type highlights an increase in the frequency of this climatic hazard in the northern and central parts of the country during January-March (JFM) season in the near and far futures. The dry/warm mode will increase in the central and southern parts of the country during the near future and in the whole country during the far future. These increase in compound extremes could lead to an increase in droughts and natural disasters over the country and could have a negative impact on socio-economic activities, such as transportation and agricultural production. This work could provide decision support for political decision-makers in formulating future public policies for managing agricultural production, food security, and natural disasters.

Toxicity mechanisms of per- and polyfluoroalkyl substances (PFAS), a chemical class present in diverse ecosystems, are not well characterized in aquatic species. Perfluorooctanesulfonamide (PFOSA, C8H2F17NO2S) is a common precursor of perfluorooctane sulfonic acid (PFOS), a long-chain PFAS. Here, we assessed sub-lethal endpoints related to development, oxidative stress, locomotor activity, and gene expression in zebrafish embryos and larvae following continuous exposure to PFOSA beginning at 6 hours post fertilization (hpf). PFOSA decreased survival in fish treated with 1 µg/L PFOSA, however the effect was modest relative to the controls (difference of 10%). Exposure up to 10 µg/L PFOSA did not affect hatch rate, nor did it induce reactive oxygen species in 7-day-old larvae fish. However, locomotor activity of larval fish treated with 100 µg/L PFOSA was reduced relative to the solvent control. Transcripts related to oxidative stress response and apoptosis were measured and BCL2 associated X, apoptosis regulator (bax), cytochrome c, somatic (cycs), catalase (cat), superoxide dismutase 2 (sod2) were induced with high concentrations of PFOSA. Genes related to neurotoxicity were also measured and transcript levels of acetylcholinesterase (ache), elav-like RNA binding protein 3 (elavl3), growth associated protein 43 (gap43), synapsin II (syn2a), and tubulin 3 (tubb3) levels were all increased in larval fish with higher PFOSA exposure. This study contributes to our knowledge regarding the relative toxicity of PFOSA to fish and contributes data to future risk assessment strategies of these concerning, persistent environmental pollutants.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

The effect of ceria doping of (ZrO2)1-x(Sm2O3)x crystals on their phase composition, microhardness and fracture toughness has been studied. The (ZrO2)0.995-х(Sm2O3)х(СеО2)0.005 crystals (where x = 0.032, 0.037 and 0.04) have been grown using directional melt crystallization in cold skull. The phase composition and structure of the crystals have been studied using X-ray diffraction, TEM and Raman spectroscopy. The mechanical properties such as microhardness and fracture toughness have been studied using Vickers indentation. It has been shown that the (ZrO2)0.995-х(Sm2O3)х(СеО2)0.005 solid solution crystals contain both Се4+ and Се3+ ions. Phase analysis data suggest that СеО2 doping increases the tetragonality degree of the transformable t phase and reduces the tetragonality degree of the non-transformable t' phase as compared to the (ZrO2)1-x(Sm2O3)x crystals. As a result, the t→m phase transition triggered by the indentation-induced stress in the СеО2 doped crystals is more intense and covers greater regions. СеО2 doping of the solid solutions increases the fracture toughness of all the crystals studied whereas the microhardness of the crystals changes but slightly. СеО2 doping of the (ZrO2)1-х(Sm2O3)х solid solutions in the experimental concentration range does not improve the high-temperature phase stability of the crystals and does not prevent high-temperature degradation of their fracture toughness.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

Electronic devices called epiretinal prosthesis are used to restore vision in patients with age-related macular degeneration (AMD) and retinitis pigmentosa (RP), two degenerative retinal illnesses. It functions by stimulating the retina's surviving cells, which then excite the brain to receive visual information from the retina. Epiretinal prosthesis have the flexibility of electrode placement, which enables them to target particular regions of the retina. Furthermore, it enables a high level of spatial resolution, enhancing visual quality. For the purpose of activating retinal cells, it transforms visual input into electrical signals. In general, epiretinal prosthesis are a potential method for helping people with degenerative retinal illnesses regain their vision. Ongoing research aims to increase the effectiveness and safety of these devices.