Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and multi-organ damage. Toll-like receptor 7 (TLR-7) and autophagy have been implicated in SLE pathogenesis. Rice husk silica liquid (RHSL) has shown potential for modulating inflammatory responses, but its effects on SLE have not been thoroughly investigated. This study aims to evaluate the impact of RHSL on immune responses and autophagy in an in vitro model of SLE, focusing on its effects on TLR-7 signaling, cytokine production, and autophagy modulation. RAW264.7 cells and human peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients were used. Cells were stimulated with LPS or TLR-7 agonists and treated with RHSL. Cell viability was assessed, and cytokine levels (TNF-α and IL-6) were measured by ELISA. Autophagy-related proteins (LC3II, ATG5-ATG12) were analyzed by Western blotting. The effect of autophagy inhibition was studied using 3-methyladenine (3-MA). RHSL did not affect cell viability but significantly reduced TNF-α production in LPS- and TLR-7 agonist-stimulated RAW264.7 cells and PBMCs. RHSL enhanced autophagy, as evidenced by increased LC3II and ATG5-ATG12 conjugation in both RAW264.7 cells and SLE patient-derived PBMCs. The reduction in TNF-α production by RHSL was attenuated by 3-MA, indicating that autophagy plays a role in this process. RHSL also inhibited the translocation of phosphorylated NF-κB into the nucleus, suggesting a mechanism for its anti-inflammatory effects. RHSL exhibits potential as an immunomodulatory agent in SLE by enhancing autophagy and modulating TLR-7 signaling pathways. These findings suggest that RHSL could offer therapeutic benefits for managing inflammatory responses in SLE and warrant further investigation into its clinical applications.

Currently, there is a marked increase in the importance of the environmental and cultural ecosystem services of the forest. Among the social benefits, protection of human health and improvement of human well-being come to the fore. Forests, both reserve and commercial, benefit human health. However, people often have negative attitudes toward forest management activities, especially near urban areas, and prefer forest management that results in a forest that is close to natural. Second-growth forest and clear-cutting are the most visible manifestations of ongoing forest management in forests. The purpose of this study was to compare the benefits derived from exposure to second-growth forest, clear-cutting and mature forest stands. Fifty-five students of the Warsaw University of Life Sciences-SGGW (WULS-SGGW) participated in the study. The study was conducted in October 2023 in a forest within the city of Otwock, within the range of the Warsaw metropolitan area. Participants were exposed for 15 minutes to selected plots: second- growth forest, clear-cutting area and mature forest stand. Before the experiment (PRE-Test control trial) and after each of the exposures four psychological questionnaires were administered: the Positive and Negative Affect Schedule (PANAS), the Restorative Outcome Scale (ROS), the Subjective Vitality Scale (SVS) and Profile of Mood States (POMS). The results indicate that not all analyzed features of the forest landscape have a regenerative effect on people. Exposure to a commercial forest, only in the case of a mature stand, yielded the most benefits in terms of mood improvement. In contrast, exposure to clear-cutting area resulted in a decrease in positive feelings and an increase in negative feelings, leading to a complete disturbance of mood, an increase in tension, depression and a decrease in feelings of vigor. Clear-cutting area has significantly worse restorative properties compared to mature forest stands and second-growth forest. This observation is relevant to forest management within city limits and in the suburban zone of large cities. Not only is clear-cutting area not accepted by people visiting forests for recreational purposes, but it leads to a detraction from the health benefits provided by forests.

Knowledge of the genetic diversity of the available germplasm is an important foundation for crop conservation, management, and improvement. Successful breeding strategies rely on a sound understanding of the genetic diversity of the crop germplasm. This study was conducted to evaluate and compare the genetic diversity of 49 soybean [Glycine max (L.) Merrill] genotypes using SSR markers as well as to evaluate parental potential of these genotypes in cultivar improvement. The bulk of the genotypes were developed in the national soybean breeding program in Zimbabwe between 1940 and 2013. The genetic diversity and relatedness were estimated using 30 SSR markers and produced 5 clusters that generally matched the pedigree information of the germplasm. The SSR analysis detected a total of 135 alleles. The polymorphic information content ranged from 0.10 to 0.77 with a mean of 0.45. The SSR primer, Satt012 was the most informative. The SSR marker analysis showed a wide genetic diversity in the germplasm. To date, there are no reports regarding the genetic diversity analysis of soybean germplasm in Zimbabwe. The genotypes, EL41 and EL7; EL41 and EL1; as well as EL41 and EL42 were the most divergent thus, indicating their potential use as parental lines in the genetic improvement of soybean in the region.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

The escalating global population and subsequent demand for agricultural products have led to a surge in agricultural waste generation, posing significant disposal challenges. Conventional disposal methods such as burning and dumping not only harm the environment but also jeopardize human health and safety. Recognizing the urgent need for sustainable waste management, researchers have increasingly focused on repurposing agricultural plant waste as a valuable resource. This paper presents a comprehensive review of the potential of agricultural plant waste in wealth creation and sustainable development. It highlights the detrimental impacts of current disposal methods and emphasizes the necessity for alternative approaches. By analyzing the physical, mechanical, and chemical properties of plant fibers, particularly cellulose, hemicellulose, and lignin, this review underscores their suitability for diverse applications. Moreover, it explores the emerging trend of utilizing pineapple leaf fiber, a sustainable and lightweight material, in structural applications such as UAV construction. With its exceptional mechanical properties and biodegradability, pineapple leaf fiber holds promise as a viable alternative to traditional materials, contributing to a more sustainable future. In conclusion, this review advocates for a paradigm shift towards embracing agricultural plant waste as a valuable asset for economic prosperity and environmental sustainability. It underscores the importance of continued research and technological advancements to unlock the full potential of agricultural waste in fostering a circular economy and driving sustainable development globally.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

To explore impact of weight change (WC) on risk of atherosclerosis measured by cIMT, 20,700 participants from the CLSA follow-up were included in analysis. WC was defined as the difference of weight measured at follow-up and baseline, then quartered into four groups (Q1–Q4). cIMT>1.0 mm was defined as high-risk for atherosclerosis. Adjusted odds ratio (OR, [95% CI]) from logistic regression models were used to evaluate the association between WC and risk of atherosclerosis. At follow-up, participants have gained 0.118 kg weight, on average, and 16.4% of them were at high-risk for atherosclerosis. The mean levels of cIMT were comparable between participants from Q1 to Q4. Compared to Q2 (reference), the ORs (95% CI) were 1.00 (0.86, 1.15), 1.19 (1.03,1.38), and 1.25 (1.08,1.45) for Q1, Q3, and Q4, respectively. A similar pattern was observed when analyses conducted by <65 vs. 65+ years separately, but it was weaker for those aged 65+ years. Results from the jointed distribution analyses indicated that weight loss might increase risk for atherosclerosis among participants with obese at baseline, but not for those with cardiovascular events status at baseline. Weight gain, however, would increase risk for atherosclerosis regardless of cardiovascular events status, or overweight/obese at baseline.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

The forest is a complex and dynamic ecosystem that requires integrated planning and management, considering economic, social, environmental, and ecological dimensions. Different stakeholders often have conflicting goals, making optimal management decisions challenging. This study aims to balance increasing economic benefits for forest users with reducing negative environmental impacts, aligning the interests of managers, government institutions, and policymakers. To achieve this, multi-objective optimization methods and game theory were used. The objectives were to maximize the net present value of wood harvesting and the amount of carbon sequestration. The study was conducted in the Shafarood forest in northern Iran. Data collected included stumpage prices, variable harvesting costs, tree density per ha, volume per ha, growth rates, interest rates, carbon sequestration, and labor costs. Using this data, models were developed for the expected mean price of various species, stored carbon, logistics growth, and labor. After adjusting the objective functions and model constraints, the range of Pareto optimal solutions for the multi-objective model and the Nash equilibrium for the game theory model were determined using the epsilon-constrain method. The results indicate that both modeling approaches can identify optimal points for balancing economic and environmental goals. The Pareto optimal range and Nash equilibrium allow for informed decision-making in managing the Hyrcanian forests, accommodating different user goals. Therefore, both models are effective tools for forest management planning and provide a framework for achieving sustainable management practices.

Background: Due to the importance of Avicenna in the history of philosophy and his special views and ideas, the views of this philosopher have always been examined by scholars and researchers. This is why many researchers have been published in connection with Avicenna's philosophy. Thereby, the comprehensive study in relation to the review of previous studies about philosophy of Avicenna is important. Methods: The Web of Science Core Collection has been used to review documents, and the data has been analyzed in VOSviewer. Results: Based on the findings in the WoS and also the maps made by VOSviewer, Types of documents, languages, documents per year, countries, journals, authors, citations, and keywords were analyzed, and based on these data and analysis the limitations of studies are realized.

Recently, polyacetylene (PA) is receiving a renewed scientific attention due to its electrical properties potentially useful for energy applications (e.g., fabrication of electrodes for batteries and supercapacitors) and unique functional characteristics (e.g., flame retardant, oxygen scavenger, EMI-shielding, etc.). This chemical compound can be obtained in form of a polyacetylene-PVOH copolymers simply by chemical dehydration of poly(vinyl alcohol) (PVOH), which is a very common type of polymer, widely used in packaging and other technological areas. This very inexpensive chemical reaction for the large-scale synthesis of PA/polyvinylenes has been investigated by reacting PVOH with fuming sulfuric acid at room temperature. In this process, PVOH, shaped in form of film, is dipped in fuming sulfuric acid (i.e., H₂SO₄ at 95-97%) and, after complete chemical-dehydration, it has been mechanically removed from the liquid phase by using a nylon sieve. The reduction process leads to a substantial PVOH film conversion to PA as it has been proved by infrared spectroscopy (ATR-mode). Indeed, the ATR spectrum of the reaction product included all characteristic absorption bands of PA. The reaction product has been also characterized by UV-Vis spectroscopy in order to evidence the presence in the structure of conjugated carbon-carbon double bonds of various lengths. Differential scanning calorimetry (DSC) and thermogravimetric analysis have been used respectively to investigate the PA solid-state cis-trans isomerization and thermal stability in air and nitrogen, respectively.

The issue of climate change represents a significant global risk that demands immediate attention. However, higher education frequently fails to incorporate global perspectives and intricate transdisciplinary matters. In order to integrate global and transdisciplinary aspects into the curriculum of a technical university with a focus on computer science, a Master's programme has been developed. The programme's objective is to situate global risk at the core of the curriculum, thereby encouraging scientists to work beyond the boundaries of their respective disciplines. The paper considers the challenges that science and higher education must address to facilitate pathways towards a peaceful and sustainable future. It argues for a shift in focus from short-term and localised issues to a more holistic approach, emphasising the importance of considering universal problems. The curriculum, as developed, may be regarded as a guide for future university efforts in the fields of global risk and climate change.

To address the problems of lining cracking and spalling of tunnel structures in coastal areas under the influence of special geologic conditions, environmental loading, and the coupling effect of chemical erosion effects, hybrid fibers were introduced to fly ash concrete in this study. The working performance, compressive strength, split tensile strength, and flexural strength of the hybrid fiber fly ash concrete were tested.The NEL chloride diffusion coefficient under steady-state conditions and the durability test for resistance to sulfate corrosion were carried out. Thus, in-depth analyses of the comprehensive performance of the hybrid fiber fly ash concrete used for tunnel lining were carried out and the damage mechanism were explored. The results showed that the hybrid fiber fly ash concrete exhibited higher strength compared to the control group concrete. However, when the fibers exceeded a certain dosage, the reduction in the working properties of the concrete structure led to the creation of larger pores in the matrix structure, which in turn affected the mechanical properties of the concrete. The most significant reduction in NEL chloride diffusion coefficient was observed when both steel fibers and coconut fibers were added at 1.0 % volumetric parameter, compared to the control group. The apparent state and compressive strength after sulfate corrosion were also minimally affected. This study ensured that the mechanical properties of the concrete were improved and also substantially improved the corrosion resistance of the matrix, providing a scientific basis for the performance improvement of tunnel lining concrete, confirming that steel-coconut fibers hybrid fiber fly ash concrete has a great potential to improve the structural load bearing capacity and durability, and may provide theoretical support for the continued use of tunneling projects and construction processes.

Generative adversarial networks (GANs) have become a recent and rapidly developing research topic in Machine Learning. Since their inception in 2014, a significant number of variants have been proposed to address various topics across many fields, and has particularly excelled not only in image and language processing, but also in the medical and data science domains. In this paper, we aim to highlight the significance and advance that these GAN models can introduce in the field of Business Economics, where they have yet to be fully developed. To this end, a review of the literature of GANs is presented in general together with a more specific review in the field of Business Economics wherein only a few papers can be found. Furthermore, the most relevant papers are analysed in order to provide an approach the opportunity to research into GANs in the field of Business Economics.

This study presents a comprehensive review of the development and progression of autonomous underwater vehicles (AUVs) in polar regions, aiming to synthesize past experiences and provide guidance for future advancements and applications. We extensively explore the history of notable polar AUV deployments worldwide, identifying and addressing the key technological challenges these vehicles face. These include advanced navigation techniques, strategic path planning, efficient obstacle avoidance, robust communication, stable energy supply, reliable launch and recovery, and thorough risk analysis. Furthermore, the study categorizes the typical capabilities and applications of AUVs in polar contexts, such as under-ice mapping and measurement, water sampling, ecological investigation, seafloor mapping, and surveillance networking. We also briefly highlight existing research gaps and potential future challenges in this evolving field.

Evaluating the economic and environmental effects of farmers' green production behaviors holds important reference value for promoting sustainable agricultural development, alleviating agricultural non-point source (NPS) pollution, and achieving the organic combination of environmental protection and economic development. This paper utilizes survey data from 1,345 farm households in the main rice production areas of Jiangxi Province, China, using the example of reduced fertilizer application (RFA) among rice farmers. By constructing a DEA—SBM model with undesirable outputs to measure environmental effects, and applying an endogenous switching model to test the economic and environmental effects of farmers' adoption of green production technologies. The study found that: (1)The behavior of RFA by farmers has a significant positive impact on their net profit per mu(NPPA), helping farmers increase their income, with the increase ranging from 2.05% to 6.54%. (2)The behavior of RFA by farmers has a significant positive impact on agricultural green productivity(AGP), contributing to the improvement of the environment, with the improvement ranging from 44.09% to 45.35%. (3)Heterogeneity analysis found inconsistencies in the income-enhancing and environmental-enhancing effects at different quantiles of NPPA and AGP. Therefore, attention should be placed on improving the agricultural product quality supervision system under the market circulation mechanism, creating land scale conditions conducive to the promotion and application of fertilizer reduction technologies, and promoting the implementation of externality internalization compensation systems.

For the set of probability measures ${\sf I}(X)$, where $X$ is a compact Hausdorff space, we propose a new way to introduce the topology by using open subsets of the space $X$. Then, among other things, we give a new proof that for a compact Hausdorff space $X$ the space ${\sf I}(X)$ is also a compact Hausdorff space. For a Tychonoff space $X$, we consider the topological space ${\sf I_{\tau}}(X)$ of $\tau$-smooth idempotent probability measures on $X$,and show that the space ${\sf I_{\tau}}(X)$ is \v{C}ech-complete if and only if the given space $X$ is \v{C}ech-complete.

In the realm of high-pressure vessel simulation, conventional finite element method (FEM) approaches, as per ASME standards, may inadequately predict the behavior of flat surfaces under elevated temperatures. This study challenges the efficacy of shell-type mesh modeling for high-temperature flat plates, demonstrating that the thermal conditions within such high-pressure vessels can induce thermal instability and buckling, not accounted for by traditional FEM methods recommended by ASME. Through comprehensive analytical investigations, we reveal that traditional shell-type meshing techniques, while suitable for certain applications, fail to capture the intricate thermal stresses and deformation patterns inherent in high-temperature flat plate configurations. Our analysis delineates distinct stability regimes governed by key design parameters—including plate thickness, operating temperature, and geometric dimensions—profoundly impacting the structural integrity of heating plates under thermal loading. By elucidating these stability boundaries, this research provides engineers with critical insights necessary for optimizing the design and performance of high-temperature equipment. This includes the design of high-pressure vessels with flat surfaces for heating materials, flanges in high-temperature environments, and fins in heat exchangers across various industries such as oil and gas, pyrolysis, and power plants. The findings presented herein serve as a valuable reference for engineers seeking to comprehend and mitigate instability phenomena in solid mechanics, offering practical guidance for developing robust and reliable high-temperature structures in demanding industrial environments.

Objective biomarkers have been a critical challenge for the field of psychiatry, where diagnostic, prognostic and theranostics assessments are still based on subjective narratives. Psychopathology operates with idiographic knowledge and subjective evaluations incorporated into clinical as-sessment inventories, but is considered to be a medical discipline and, as such, uses medical in-tervention methods (e.g., pharmacological, ECT; rTMS; tDCS), and therefore is supposed to oper-ate with the language and methods of nomothetic networks. The idiographic assessments are pro-visionally “quantified” into “structured clinical scales” to in some way resemble nomothetic measures. Instead of fostering data merging and integration, this approach further encapsulates the clinical psychiatric methods, as all other, biological tests (molecular, neuroimaging) are per-formed separately, only after the clinical assessment has provided diagnosis. Translational cross-validation of clinical assessment instruments and fMRI is an attempt to address the gap. The aim of this approach is to investigate whether there exist common and specific neural circuits, which underpin differential item responses to clinical self-rating scales during fMRI session in pa-tients suffering from the two main spectra of mental disorders: schizophrenia and major depres-sion. The current status of this research program and future implications to promote the devel-opment of psychiatry as a medical discipline are discussed.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

The utilization of optical antennas for active control of far-field radiation at the subwavelength scale is crucial in various scientific and technological applications. We propose a thermally tunable disk design of indium tin oxide (ITO) and aluminum gallium nitride (Al0.18Ga0.82As), enabling a switch between absorption and scattering. Furthermore, the control of far-field radiation pattern can be easily realized by combining ITO and Al0.18Ga0.82As to enhance or suppress emission. Our results demonstrate that hybrid structure can be dynamically tuned with temperature variations. In the proposed design, a frequency is achieved at the epsilon-near-zero wavelength of 1240 nm. The thermal tunability of hybrid structure introduces new multifunctional possibilities for light manipulation, thereby enhancing the potential applications of new devices in the near-infrared range.

DFT calculations on the photoisomerization reactions of pyridazine N-oxide derivatives are presented. The irradiation of 3,6-diphenylpyridazine N-oxide allowed to obtain the first excited singlet state that underwent to a ring opening reaction induced to the oxygen migration to the adjacent carbon atom, with the formation of a diazo derivative. This intermediate can give a ring closure reaction to give a pyrazole derivative, or, with a higher transition energy, it can lose nitrogen allowing the formation of 2,5-diphenylfuran. The irradiation of 3-phenylpyridazine N-oxide allowed the formation only of 2-phenylfuran. In this case, calculations allowed to explain this behavior. The first excited singlet state gave a photoisomerization reaction with the formation of the corresponding diazo intermediate. This intermediate could not be converted into the corresponding pyrazole derivative because it was converted into a N-formyl pyrazole never reported in literature. The only possible reaction is the loss of nitrogen and the formation of 2-phenylfuran.

This study aims to provide empirical evidence on whether using renewable and non-renewable energy, CO₂ emissions and the resulting changes in temperature and precipitation can alter cereal yields in European Union countries. To this end, a panel data set covering 1992-2021 has been used to analyse the impact of climate change and economic factors on cereal production in European Union countries. The study employed various analytical techniques to understand better the relationship between climate change, energy consumption, and economic growth. These included using annual average temperature and rainfall to measure climate change and energy consumption and economic growth to analyse the economic aspects. To achieve the objective, feasible generalised least squares (FGLS) models with robust standard errors and bootstrap and a quantile regression (QR) model with marginal analysis were employed. The Westerlund cointegration test confirmed the presence of cointegration between cereal production and climate variables, economic growth, and energy consumption. The results indicate that increases in temperature and precipitation may contribute to increased cereal production in European Union countries. In contrast, energy consumption, including renewable energy and CO₂ emissions, may have a nonlinear effect on cereal production. Quantile regression analysis suggests climate change may impact crop yields most in countries with low and moderate cereal production per hectare. Increased CO₂ emissions may increase yields in the initial period, but excessive CO₂ may negatively impact cereal production in the long term. It would be advisable for countries with low and moderate crop productivity to consider implementing technological advances and combating global warming by modernising cultivation methods and making greater use of renewable energy sources.

This research explores the behaviors of Generation Z consumers in China, particularly focusing on their interaction with companies through social media for the joint creation of value. Adopting a qualitative methodology, the research initially constructs a scale for assessing co-creation of value on social media platforms. Subsequently, it delves into the motivational aspects of users' engagement in these co-creative activities. The study unveils a range of utilitarian and hedonic motivations that drive Generation Z's value co-creation actions on social media. Insights derived from the findings offer both theoretical and practical implications for the field.

Contemporary financial systems, despite their inherent complexity and resilience, face significant challenges related to transparency, efficiency, and security. Notable deficiencies in transparency and emerging security vulnerabilities underscore the pressing need for innovative solutions in current financial practices. Hence, this paper introduces a financial distribution system based on a consortium blockchain. Given organizations’ preference for keeping sensitive data private, the partially decentralized nature of consortium blockchains plays a pivotal role in the proposed system’s architecture. Moreover, within this system, the proposed smart contract serves a dual role. It functions not only as a transactional tool but also as a specialized solution designed to improve transactional procedures. Its multifaceted capabilities include ensuring data accuracy, facilitating swift execution, and ensuring adherence to regulatory requirements within the dynamic financial distribution landscape. Through rigorous testing and empirical analysis utilizing the Hyperledger Besu platform, it has been observed that the performance of the proposed system surpasses traditional blockchain frameworks. The results unequivocally demonstrate the proposed system’s proficiency in handling high-frequency financial transactions with minimal computational burden.

Mangroves offer vital ecological advantages including air and water filtration, coastal and estuarine habitat provision, sediment stabilization, and wave energy absorption. Their intricate root systems play a key role in safeguarding shorelines from tsunamis and erosive storms by dissipating wave energy. Moreover, mangroves shield against boat wakes and wind-waves, bolstering shoreline defense. Wave dissipation is a function of forest width, tree diameter, and forest density. Restoration efforts of juvenile mangroves in Florida’s Indian River Lagoon (IRL) aim to reduce wave energy in areas vulnerable to erosion. Physical model testing of wave dissipation through mangroves is limited due to the complexity in representing the mangrove structure, where prop roots are non-uniform in both diameter and location. Previous studies have quantified wave dissipating effects through use of scaled and parameterized mangrove structures. This study measures the dissipation effects of live mangroves in a wave flume, forced by conditions representative of the IRL. These measurements are used to validate a parameterized dowel model. Error between wave attenuation factors for the live mangrove and dowel system was on average 2.5%. Validation of the modularized dowel system allowed for further parameterized testing to understand forest structure effects, such as sediment stabilization and wave attenuation.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Objective: The aim of this in vitro study was to evaluate the accuracy of resin-based fixed dental restorations, namely veneers, single crowns, and four-unit fixed partial dental prosthesis (FPDs) using two different 3D printers and polymer-based materials. Materials and Methods: A standard maxillary polyurethane jaw model containing prepared teeth was scanned using an intraoral scanner. The generated STL data were used to design the restorations virtually using CAD software. Two 3D printers were utilized for the provisional digital light processing and stereolithography for the castable resin patterns. Each printer produced 10 specimens of each type of restoration, for a total of 80 restorations. The 3d-printed restorations were then 3D scanned using the same intraoral scanner and evaluated for external and internal dimensional accuracy in terms of trueness and precision. A one-way ANOVA and Two-sample T-Test were implemented to compute the precision (variability between groups) and trueness (with the designed CAD model). A level of statistical significance of p-Value

This study presents a novel approach for quantifying the dynamics of monthly hydraulic geometry relationships in the Jingjiang reach of the Yangtze River by integrating leaf area index (LAI) data as an indicator of riparian vegetation. A comprehensive system of ordinary differential equations (ODEs) couples traditional power-law hydraulic geometry equations with LAI, capturing the influence of erosion control on channel morphology. The periodic delayed response theory and automatic differentiation techniques are employed to enhance the modeling framework's capabilities. Calibration and verification demonstrate the models' effectiveness in capturing overall trends in discharge, width, and depth dynamics, outperforming traditional constant-parameter approaches. However, model predictive abilities are limited under extreme climate conditions due to training on normal climate data. Key assumptions, including the periodic delayed response theory's neglect of peak discharges, simplified representation of artificial cut-offs, and reliance on remotely sensed data with limited local validation, introduce uncertainties. The proposed modeling framework shows potential for broader application to other river systems with appropriate adjustments. Future research could incorporate additional environmental factors, integrate models across scales, couple with advanced simulation techniques, and expand stability assessments beyond the riverbed index. By addressing related challenges, this integrated approach lays a foundation for enhancing understanding of river morphodynamics and channel stability.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

Considering the spectrum shortage problem of IoT devices, we introduce a collaborative spectrum sensing (CSS) framework in this paper to identify available spectrum resources, so that IoT devices can access it and meanwhile avoid causing harmful interference to the normal communication of the primary user (PU). However, in the process of the PU’s signal detection in IoT devices, the issue about the stopping time and decision cost arises. To this end, we propose a distributed cognitive IoT model, which includes two IoT devices independently using sequential decision rules to detect the PU. On this basis, we define the stopping time and cost function for IoT devices, and formulate an average cost optimization problem in CSS. To solve this problem, we further regard the optimal stopping time problem as a finite horizon problem, and solve the threshold of the optimal decision rule by dynamic programming. At last, numerical simulation results demonstrate the correctness of our proposal in terms of the global false alarm and miss detection probability, and it always achieves minimal average cost under various cost of each observation taken and thresholds.

This study presented a novel and sustainable method for producing chitin nanocrystals (PA-ChNCs) using phosphoric acid hydrolysis. The produced PA-ChNCs were used as stabilizers for Pickering emulsions and their physicochemical properties as well as stabilization mechanisms were systematically investigated. The PA-ChNCs exhibited small particle sizes and high surface areas, enabling an effective adsorption at the oil/water interface, which prevented coalescence in Pickering emulsions. The particle size and surface charge PA-ChNCs were strongly pH-dependent, which were critical factors for stabilizing Pickering emulsions. The study showed that emulsions with higher O:W ratios (50%) exhibited larger droplets but greater viscosity, forming a stable gel-like matrix that was more stable than emulsions with other O:W ratios after storage for 30 days. Emulsions with higher PA-ChNCs concentrations (2.0 wt%) and higher pH values (pH 10) showed small droplets and high viscosity, leading to stable emulsions. This research contributes to the development of sustainable and effective emulsifiers for use in the food industry, making utilization of seafood waste in an eco-friendly manner possible. Overall, this study highlights the potential of using newly developed PA-ChNCs as stabilizers for Pickering emulsions in food products.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

Management of chronic inflammation and wounds has always been a key issue in the pharmaceutical and healthcare sector. Curcumin (CCM) is an active ingredient extracted from turmeric rhizomes that has antioxidant, anti-inflammatory, and antibacterial activities, thus showing significant effectiveness toward wound healing. However, its shortcomings such as poor water solubility, poor chemical stability and fast metabolic rate limit its bioavailability and long-term use. In this context, hydrogels appear to be a versatile matrix for carrying and stabilizing drugs due to the biomimetic structure, soft porous microarchitecture, and pleasant biomechanical properties. The drug loading/releasing efficiencies can also be controlled by use of highly crystalline and porous metal organic frameworks (MOFs). Here, a flexible hydrogel composed of sodium alginate (SA) matrix and CCM-loaded MOFs was constructed for long-term drug release and antibacterial activity. The morphology and physicochemical properties of composite hydrogels were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet visible spectroscopy (UV-Vis), Raman spectroscopy and mechanical property tests. The results showed that the composite hydrogel was highly twistable and bendable to mechanically comply with human skin. The as-prepared hydrogel could capture efficient CCM for slow drug release as well as effective killing of bacteria. Therefore, such composite hydrogel is expected to provide a new management system for chronic wound dressings.

In this work, we report the electric energy storage properties of (1-x)Bi0.5(Na0.8K0.2)0.5TiO3-xBi0.2Sr0.7TiO3 (BNKT-BST; x = 0.15-0.50) relaxor ferroelectric ceramics enhanced via a domain engineering method. A rhombohedral–tetragonal phase, the formation of highly dynamic PNRs, and a dense microstructure are confirmed from XRD, Raman vibrational spectra, and microscopic investigations. The relative dielectric permittivity (2664 at 1 kHz) and loss factor (0.058) were gradually improved with BST (x=0.45). The incorporation of BST into BNKT can disturb the long-range ferroelectric order, lowering the dielectric maximum temperature Tm and inducing the formation of highly dynamic polar nano-regions. In addition, the Tm shifts toward high temperature with frequency and a diffuse phase transition, indicating relaxor ferroelectric characteristics of BNKT-BST ceramics, which is confirmed by the modified Curie Weiss law (γ=1.83). The rhombohedral–tetragonal phase, fine grain size, and lowered Tm with relaxor properties synergistically contribute to a high recoverable energy density Wrec of 0.81 J/cm3 and a high energy efficiency η of 86.95% at 90 kV/cm for x = 0.45.

Practical applications of CsPbX3 nanocrystals (NCs) are limited by their poor stability. The formation of heterojunction between CsPbX3 NCs and oxides is an effective means to protect perovskite from polar solvents and other external factors. Significantly improving the stability and photocatalytic properties of the core/shell perovskite is very important for its application in photoelectric and photocatalytic technology. Here, we report the synthesis of asymmetrical CsPbBr3/TiO2 core-shell heterostructure NCs at single particle level by hot injection liquid phase synthesis and sol-gel method, where each CsPbBr3 NCs is partially covered by titanium dioxide. It is shown that the type II arrangement is generated at the heterogeneous interface, which greatly facilitates the separation of electron-hole pairs and increases the carrier transport efficiency. More crucial, due to the protection of titanium dioxide shell, the product has higher long-term stability in humid air compared with bare CsPbBr3 NCs. The asymmetrical core-shell heterostructure prepared in this study not only improves the stability of CsPbX3 NCs, but also provides some ideas for optoelectronic device applications and TiO2-based photocatalysts.

In this nano era, nanomaterials and nanostructures are popular in developing novel functional materials. However, the combinations of nanoproducts with materials at micro and macro scale can open new routes for conceiving novel materials with an improved or even new functional performances. In this study, a brand-new hybrid, containing both nanofibers and particles having a microsize, was fabricated using a sequential electrohydrodynamic atomization (EHDA) process. Firstly, the microparticles loaded with drug (berberine hydrochloride, BH) molecules in the cellulose acetate (CA) were fabricated using a solution electrospraying process. Later, these microparticles were suspended into a co-dissolved solution containned BH and a hydrophilic polymer (polypyrrolidone, PVP), and were co-electrospun into the nanofiber/microparticle hybrids. The EHDA processes were clearly recorded, and the resultant products showed a typical hybrid topography, with microparticles distributed all over the nanofibers, which was demonstrated by SEM assessments. FTIR and XRD demonstrated that the components within the hybrids were presented in an amorphous state and have fine compatibility with each other. In vitro dissolution tests verified that the hybrids were able to provide the designed dula-step drug release profiles, a combination of the fast release step of BH from the hydrophilic PVP nanofibers through an erosion mechanism and the sustained release step of BH from the insoluble CA microparticles via a typical Fickian diffusion mechanism. The present protocols pave a new way for developing trans-scale functional materials.

Human Papillomavirus (HPV) self-sampling has the potential to increase cervical cancer screening (CCS) and reduce the cervical cancer burden in Medically Underserved Women (MUW). However, interventions promoting self-sampling are limited. We examined the effectiveness of an intervention study in increasing CCS among MUW. We conducted a quasi-experimental intervention study. Face-to-face verbal approach was to recruit MUW (n=85, mean age 48.57±11.02) living in a small city in the US. Behavioral intervention based on reframing, reprioritizing, and reforming (3R model) was used to educate the women about CCS in a group format. The women completed pre-and post-intervention assessments and followed-up interviews. The primary outcome was CCS uptake. Mixed methods analyses were conducted using a t-test for the primary outcome, PROCESS for mediation analysis, and NVivo for interview data. Majority of women (75%) completed self-testing. High-risk HPV prevalent among the women was 11%, and of those, 57% followed-up with physicians for care. We found that the significant increase in the women’s post-intervention screening behaviors was mediated by the increase in knowledge (Indirect Effect [IE] = .1314; 95% CI, .0104, .4079) and attitude (IE = .2167; 95% CI, .0291, .6050) scores, (p&lt;0.001). Interview analyses offered further explanations (see the explanations in parenthesis) why MUW found the intervention messages acceptable (encourages proactive behavior), feasible (simple and easy to understand), and appropriate (helpful and informative). Barriers including lack of trust and fear of results were identified. The findings suggest that an intervention that combines the 3R model and self-sampling may increase CCS among MUW.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

In August 4 2011, United Nations Environmental Program (UNEP) submitted an unprecedented, scientific, groundbreaking Environmental Assessment Report (EAR) of Ogoniland, to the Nigerian government. This was the outcome of a 14–month intensive evaluation of the extent of pollution. It was intended that UNEP’s recommendations would be implemented to restore the devastated environment, on the one hand, and on the other, counteract the numerous environmental health issues that have for decades, plagued Ogoniland. However, five years post EAR, and, despite the seriousness of the situation, no significant resolution has occurred, both on the part of the government, and on the part of Shell Petroleum Development Company (SPDC) or Shell. To date, millions of Niger Delta residents, particularly those living in the oil-bearing communities, continue to suffer severe consequences. Although, the assessment was conducted in Ogoniland, other communities in the Niger Delta are also affected. This article explores prevailing issues, using Ogoniland (a microcosm of the Niger Delta) as an example. A multidisciplinary approach for sustainable mitigation of environmental health risks in the Niger Delta is paramount, and Environmental Management tools offer valuable strategies. Adopting UNEP’s recommendations for addressing environmental health problems requires implementing the Environmental Management/Environmental Management System (EM/EMS) model.

A compact Mach-zehnder interferometer with a novel design of directional couplers and a phase shifter has been presented as a thermo-optical sensor. With the aim of reducing device size to micro and nano dimension silicon-on-insulator technology was employed. That allowed miniaturization of device size through the reduction of its cross sectional area to 0.066 µm² and the radius of curvature of both the arms of the directional coupler and S-bends of the phase shifter to 5 µm and C-bends to 3 µm. These nano size device dimensions made it possible to reduce the coupling gap to 0.2 µm, which resulted in a significant reduction in the coupling length. The device geometry and its performance characteristics were analyzed and optimized using coupled mode analysis and finite difference time domain simulation tools, respectively. The wavelength dependent transmission loss of the device was measured at different temperature to verify and validate its performance characteristics. Tested devices showed a remarkable temperature dependent transmission characteristic offering significant changes in transmission loss band – with as low as 0.45 ⁰C change in substrate temperature. The extinction ratio and the free spectral range of the device were 26 dB and 0.26 nm respectively in the wavelength range of 1549.5 nm – 1550.5 nm. These results imply that the devices presented here can be used as compact and highly sensitive thermal sensors and optical switches.

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG combined with the anti-PD1 inhibitor Cemiplimab is under Phase 2 clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4+ and CD8+ T cells while reducing regulatory T cells, indicating immune system enhancement. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.

Cervical cancer (CC) remains a significant global health challenge, characterized by its genetic heterogeneity and complex molecular landscape. The current study investigates the germline variants in proto-oncogenes and tumor suppressor genes among patients diagnosed with cervical cancer. Utilizing a custom NGS panel targeting 48 genes implicated in oncogenesis, we identified 148 nucleotide sequence alterations across the cohort. Of these, 35 variants (23.6%) were classified as benign, while 105 (70.9%) were categorized as variants of uncertain significance (VUS), whose clinical relevance remains to be elucidated. Moreover, we discovered seven pathogenic or likely pathogenic mutations, as well as a polymorphic variant rs1042522 in the TP53 gene, which has been previously associated with an increased risk of CC. Our findings contribute to the understanding of the molecular-genetic landscape of cervical cancer, highlighting the potential impact of rare germline mutations on the disease's pathogenesis and progression. This study underscores the importance of comprehensive genetic screening in improving the diagnostic and therapeutic strategies for cervical cancer patients.

This study investigates the phytochemical profile, cytotoxic effects, and lactogenic activity of Oxystelma esculentum, a plant renowned for its traditional medicinal uses. Preliminary phytochemical screening revealed a rich array of secondary metabolites, including alkaloids, flavonoids, glycosides, and tannins, predominantly in polar solvents such as methanol and ethanol. Spectroscopic analysis further identified key functional groups, suggesting significant bioactivity. The cytotoxic potential was evaluated against ovarian (OVCAR3), breast (T47D), and cervical (HeLa) cancer cell lines, demonstrating a concentration-dependent increase in cytotoxicity, with T47D cells exhibiting the highest sensitivity (IC50 = 42.82 μg/ml). Additionally, the brine shrimp lethality assay indicated low toxicity, while in vivo studies highlighted the extract's ability to enhance milk yield and pup growth in lactating rats, correlating with increased prolactin levels. These findings underscore Oxystelma esculentum as a promising candidate for natural anticancer therapies and lactation enhancement, warranting further exploration of its bioactive compounds and mechanisms of action.

In this study, Caciocavallo Ragusano, a typical cheese produced in Sicily Island (Italy), was ob-tained from milk of dairy cows fed with and without enriched olive cake (ECO and CTR, respec-tively) in order to evaluate nutritional, microbiological, volatile, and sensory differences in cheeses. ECO cheese showed greater (p < 0.05) MUFA and PUFA and polyphenols content, and lower SFA content than CTR cheese. Microbiological analyses revealed the absence of Salmonella, Listeria monocytogenes, Escherichia coli, and E. coli O157, and no significant differences in the vi-able counts of the remaining microbial groups analyzed, between samples. Thermophilic lacto-cocci were more prevalent in ECO cheese. The implementation of culture-independent method, such as PCR-DGGE analyses, revealed the presence of a more diverse microbial population in both cheeses. Regarding the volatile compounds profile, long-chain free fatty acids were more abundant in the ECO cheese resulting in a healthier free fatty acid profile. This study also showed that, especially for their appearance and taste, the consumers mostly appreciated the ECO cheese. Results showed that using enriched olive cake could enhance the sustainability and the quality of Ragusano cheese, improving not only the health of the consumers but also positively influencing tastes and acceptability.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Introduction: Management of hypoxic-ischemic encephalopathy (HIE) has been the subject of international recommendations. However, some aspects remain within the realm of service practices and appear to vary greatly from one center to another. Objectives: To achieve a multidisciplinary consensus in France regarding management of HIE newborns that are not covered by international and national guidelines. Methods: This is a prospective, multicenter study using the Delphi method from April 21, 2021, to July 15, 2021. Perinatal professionals were contacted through professional societies. Participants received a questionnaire in three successive rounds. Each proposal was rated using a Likert scale from 1 (completely disagree) to 8 (completely agree). An item was considered consensual if at least 70% of responses were in agreement or disagreement. Results: 58 french neonatal professionals participated. A consensus was reached in the first round concerning the use of passive hypothermia in maternity ward, with 84% agreement and to define the target temperature between 35.0°C and 35.5°C at the third round. Regarding hypoglycemia in the delivery room, 79.2% agreed in the first round to correct blood glucose levels below a threshold of <2.2 mmol/l. Parenteral route was the preferred correction method for 91.4% of respondents, while enteral route via nasogastric tube did not reach consensus. Conclusion: This study highlights the variability in definitions and practices among professionals in the management of HIE. Consensus was found regarding certain care practices performed without formal guidelines. The work to harmonize definitions and practices for the management of HIE likely needs to continue.

Traditional photodynamic therapy (PDT) is often limited in its efficacy by insufficient light penetration, inefficient photosensitizer energy transfer, and inadequate target tissue oxygenation. X-ray activated PDT (XPDT), using nanoparticle (NPs) photosensitizers comprised of europium-doped yttrium oxide cores encased within silica shells (Y₂O₃:Eu@SiO₂), offers the potential of overcoming most of these limitations. Aimed at maximizing the generation of reactive oxygen species (ROS), this study reports methodologies for investigation of the effects of synthesis conditions on the characteristics of Y₂O₃:Eu@SiO₂ NP. Transmission electronic microscope (TEM) revealed that the NP core diameter was linearly, positively correlated with condensation time (R2 = 0.7357, p < 0.05) and linearly, negatively correlated with urea concentration (R2 = 0.958, p < 0.05). The addition of cetyltrimethylammonium bromide (CTAB) during core synthesis demonstrated enhanced particle dispersion. Silica coating via APTES-1 and TEOS-3 conditions resulted in Y₂O₃:Eu@SiO₂ NPs that generated the highest ROS, with 8.7-fold and 8.9-fold increase respectively in relative fluorescence intensity at 8 Gy irradiation compared to a 5.2-fold increase in PBS under the same condition. In vivo evaluation using 18F-fluorothymidine positron emission tomography (18F-FLT PET) of mouse xenografts of a human prototypical cancer (ovarian) revealed a 55% reduction in tumor proliferation of radiation-sensitive CAOV3 tumors treated with Y₂O₃:Eu@SiO₂ NPs compared to a 19% reduction in tumor proliferation of radiation-resistant SKOV3 tumors on the fourth day post-treatment. Taken together, these findings suggest Y₂O₃:Eu@SiO₂ NPs can serve as effective photosensitizers for XPDT and their performance characteristics can be optimized by selecting synthesis conditions and parameters to deliver the desirable therapeutic effects, offering novel approaches to circumventing many of the limitations of conventional PDT in the treatment of cancer.

Milk consumption is crucial for a balanced diet, yet recent trends indicate a decline, especially in Italy. A significant factor in this decline is the altered perception of milk quality among consumers, creating a communication gap between them and other stakeholders. This study aimed to explore the discourse on social media and sentiment towards the concept of milk quality among consumers, farmers, and processors. The research adopted a Social Media Analysis to examine online community messages. A sample of 19,906 Italian comments and posts mentioning keywords Milk, Quality, Cow, and Vaccine was collected and categorized using term frequency analysis, correspondence analysis, and sentiment analysis. Results highlighted gaps in the perceptions of milk quality: farmers focused on economic issues, consumers on animal welfare and health, and processors on lactose content. For farmers, almost all comments were negative, while for processors, nearly all comments were positive. Consumers presented a more mixed picture. This work contributes to the literature by expanding research on milk quality using social media as a source of information. The findings suggest that enhancing communication and understanding among these groups could lead to more effective strategies for addressing consumer concerns, potentially reversing the declining of milk consumption.

With around one billion of the world's population affected, the era of Metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which, to date there is almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it affects also extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn®) was approved for Metabolic dysfunction associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Despite that a pharmaceutical industry is still lagging behind to develop an ap-proved pharmacologic therapy for MAFLD, research has been recently intensified and many molecules which are underway in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was ap-proved via accelerated procedure for treatment of MAFLD, i.e. of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval.

Background: Systemic autoimmune rheumatic diseases (SARDs), including Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), are characterized by chronic inflammation and autoimmunity. Identifying reliable biomarkers is crucial for enhancing diagnosis, monitoring disease progression, and evaluating therapeutic responses. This study explores the potential of serum Syndecan-1 (SDC-1) as a biomarker for these conditions and concurrently examines its relationship with free light chain (FLC) expression levels in the same patients. Methods: A retrospective analysis was performed on serum samples from 120 patients (60 RA, 60 SLE), alongside 50 healthy donors (HD). Serum levels of κ and λ FLCs were determined by turbidimetric assay, while SDC-1 levels were measured using ELISA. Statistical analyses, including the Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman’s correlation, were employed to compare biomarker levels across groups and to explore correlations among them. Results: Significantly increased levels of SDC-1, κ-FLC, and λ-FLC were observed in patients diagnosed with RA and SLE compared to HD (p < 0.001), while no significant differences in the κ/λ ratio were noted among the groups (p = 0.4). A statistically significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE statuses are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age. Conclusion: Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared to healthy controls underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cells activation, supporting the SDC-1 role in the pathogenesis of these conditions.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

This retrospective study aimed to evaluate the performance of the hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows who received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) &lt;3.75 after treatment and loose-housing cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

Bulk composition, mineralogy and microchemistry of various fractions of the filling of the Crater No. 4 at Emmerting were investigated. Here we present mainly the fine fractions, which, in contrast to pebbles larger than ca. 4 cm, are relatively poor in material affected by melting. A 0.1 mm long meteorite fragment without ablation features was found, and remelted fragments of the same body have been identified. The projectile was dominated by enstatite, also containing forsterite, basic plagioclase, Ni-rich pyrrhotite and troilite, kamacite, silica, and probably merrillite. The molten fragments contain porous Mg-rich glass (indicating temperature &gt; 1500 °C), minor Fe oxides, and occasionally uncommon Ni-rich minerals. The bulk composition and electron microprobe show that the amount of meteoritic material is low (&lt;&lt; 1 %), and it is not unequivocally manifested even in platinum-group elements abundances and osmium isotope ratios (the latter, however, were only measured in two samples). This can be explained by dilution of the filling by particles brought after the crater formation, and by probably achondritic composition of the projectile. Relatively large hollow spheroid Fe oxide particles were observed in thin sections from the magnetic fraction. A Mn oxide hollow spherule has also been found. In magnetically separated filling from the nearby Crater No. 5, bulk chemical composition points to contamination with several metals and metalloids probably due to influence of recent alluvial sediments. Therefore, the extent of meteoritic contamination in this crater may be even smaller.

In pediatric burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses polyhexamethylene biguanide (PHMB)'s role in managing superficial partial-thickness burns in children, focusing on the effects of various patient-specific factors on recovery. Through a retrospective analysis of 27 pediatric cases treated with PHMB, we explored the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the duration until reepithelialization. Notably, the majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. The study reveals a mean healing time of 8.78 days, with the extent of the burn showing a strong correlation to recovery speed. Most treatments were managed outpatient, evidenced by a negligible average hospital stay. Impressively, the intervention recorded no complications. Our findings endorse PHMB as a promising treatment for second-degree burns in young patients, offering healing efficiency on par with or surpassing traditional methods, without increasing complication risks. This investigation underscores the necessity for continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management, advocating for future research aimed at assessing long-term outcomes, including scar quality and patient satisfaction.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Introduction: In recent years, generative Artificial Intelligence models, such as ChatGPT, have been increasingly utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating a response to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. Materials and Methods: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a 5-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations' strength. Results: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models with a statistically significant difference. Post-hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. Conclusions: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

Hubble diagrams are examined for SN1a supernovae in the redshift range z = 0.01–1.3 and for gamma ray bursts in the range z = 0.034–8.1. It is shown that in the low redshift range, the Hubble diagram shows an innate equivocality between the ΛCDM and the tired light model. This means that the strong agreement between the z/µ data, calculated with the parameters of the ΛCDM model, and the experimentally measured z/µ values cannot be considered as definite evidence for the expansion hypothesis. The exponential function , which is characteristic of the tired light redshift mechanism, fits the data with similarly high accuracy. Hence, on the premise of low redshift data, a decision for or against either model is completely arbitrary. The Hubble diagram for high redshift gamma ray bursts shows poor agreement with the ΛCDM model, but concurs with the exponential energy decay following from the tired light redshift hypothesis.

Aim: This study aims to explore the collaborative networks in Marfan Syndrome (MFS) research by analyzing co-authorship patterns from 2000 to 2023. The objective is to identify key researchers, trends in collaboration, and the extent of interdisciplinary cooperation within the global MFS research community. Understanding these dynamics will inform the future direction of research in this field, emphasizing the need for a more integrated, interdisciplinary approach. Method: This study utilized network analysis techniques to evaluate 6,657 publications related to MFS research indexed in the Web of Science (WoS) Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed. Result: The network analysis revealed a persistent fragmentation within the MFS research community over the past two decades. While network density slightly increased from 0.0012 in the 2000–2009 period to 0.0016 in 2020–2023, the network remained disjointed with numerous disconnected components. Key contributors, such as Harry C. Dietz, Guillaume Jondeau, and Julie De Backer, demonstrated high centrality values, playing pivotal roles in shaping collaboration. The clustering coefficient remained high across all periods, indicating strong intra-group collaboration, yet underscoring the need for broader interdisciplinary partnerships.Conclusion: This study highlights the need for more integrated and cross-disciplinary collaboration in MFS research. Despite the significant contributions of central researchers, the overall fragmentation limits potential advancements. Fostering a more interconnected global network and encouraging interdisciplinary cooperation will be crucial to addressing the complex, multi-systemic nature of Marfan Syndrome and improving patient outcomes.

Family planning (FP) services are crucial interventions for improving maternal and child health outcomes and promoting gender equity. However, ensuring equitable access to these services remains a significant challenge, particularly in countries like Pakistan, where sociocultural norms, economic disparities, and geographic barriers hinder FP uptake. This study utilized spatial analysis techniques, including hotspot analysis, to investigate geographic disparities in FP uptake in Pakistan using data from Pakistan Demographic and Health Surveys (PDHS) conducted between 2006 and 2017. ArcMap 10.1 was used for spatial analysis and Stata 12.0 for statistical analysis. Results revealed significant spatial variations in FP uptake, with urban areas generally exhibiting higher uptake rates than rural regions. Hotspot analysis identified dynamic changes in contraceptive prevalence rates (CPR), with significant clustering in some regions and dispersion in others. It also identified areas with high unmet need and their low intention to use FP services and preference for family size (&gt;3 children), highlighting the need for targeted behavioral change interventions. This innovative spatial approach provides nuanced insights for policymakers and program planners to develop targeted interventions based on localized data to improve FP service delivery, mitigate disparities, and ultimately advance efforts to improve maternal and child health outcomes. The application of geospatial analysis is an effective tool for enhancing program planning, evaluation, and resource allocation in diverse geographical contexts.

This study aimed to conduct importance-performance analyses (IPAs) based on the perception of Korean middle-school students toward health management awareness during the post-coronavirus disease 2019 (COVID-19) era. Data were collected from 867 Korean middle-school students via online and offline surveys between May and June 2023. A frequency analysis, a reliability analysis, an IPA based on the entire target students, and an IPA depending on sex were carried out with the collected data, and they revealed the following. First, the IPA results regardless of sex indicated that four factors of the mental health were located in the third quadrant with one factor of the same variable in the fourth quadrant. The three factors of the disease management were located in the third quadrant. As for physical activity, two factors were located in the first quadrant, one in the second quadrant, and one in the third quadrant. As for sleep management, two factors were located in the second quadrant, one in the third quadrant, and one in the first quadrant. As for the eating management, two factors were located in the third quadrant, and one in the fourth quadrant. As for the social distancing variable, all four factors were located in the third quadrant. As for the hygiene management, two factors were located in the first quadrant, one in the third quadrant, and one in the fourth quadrant. Furthermore, the IPA results indicated gender differences in regular sports and vigorous movement activities associated with the physical activity. Additionally, a gender difference was observed in regular diet associated with the eating management. This study proposed possible measures for encouraging adolescents to recognize the importance of health and increase their health-related performance during the COVID-19 endemic phase.

Short-form video has taken over social media and attracted attention from advertisers. As brands shift their advertising spending to short-form video social platforms, doubts remain about the advertising efficacy on these platforms, especially given the skyrocketing advertising costs in recent years. In a large-scale randomized experiment on ByteDance in collaboration with an automobile brand, we show a significant effect of the advertising campaign on ByteDance, compared with effects reported in other studies. Exposed users are eight times more likely to convert from outside than from within ByteDance, which raises the importance of information sharing between the platform and brands. When considering conversions outside ByteDance, the average cost per conversion, which brands commonly use to evaluate the cost of campaigns, shrinks by 5 or 25 times, depending on the methods used to calculate it. Information sharing can also affect a brand’s targeting strategy. While commonly used demographic variables by the automobile brand are effective for target marketing with only platform data, they are not when considering conversions outside ByteDance. Instead, a behavioral variable proposed herein (prior brand home page visits) effectively moderates the advertising effect but has no effect when including only platform data in the analysis.

Background: The molecular domestication of the gag gene of retrotransposons and retroviruses gave rise to the Gagr gene in the genome of Drosophila. The Gagr protein has a conservative structure in all Drosophila species, suggesting an essential function. As we previously shown, the Gagr gene may play a part in immune response and processes linked to stress reactions. Methods: Tub-GAL4&gt;UAS-Gagr flies, which had the Gagr gene knockdown in all tissues, were compared with the control hybrid Tub-GAL4&gt;w1118. Gagr gene function was verified by RNA-sequencing followed by RT-PCR and physiological tests. Results: In contrast to the control strain, we observed that flies with the Gagr gene knockdown had a shorter lifespan, but the mutant strain was more resistant to heat stress. Also, the Gagr knockdown strain had higher level of transcription of the immune response genes, according to a transcriptome analysis. It has been shown that the ammonium persulfate used to induce stress causes the Toll, Jal-STAT, and Jnk/MAPK signaling pathways to become activated, which results in a systemic response in numerus tissues in the control strain. Conversely, the Gagr gene mutant strain exhibits low expression of the stress response. Enrichment of the molecular function of genes overexpressed under ammonium persulfate stress in the control strain, but not in the Gagr knockdown mutant, revealed a category with 19 transcription factors involved in the control of organism development, morphogenesis and the functioning of the central nervous system. Their expression pattern and the Gagr gene's expression pattern match. The data obtained demonstrates the importance Gagr is to maintaining both the body's immune system and homeostasis.

Three novel iron(II) coordination polymers, [Fe(H2O)2(ttmb)2](ClO4)2·4H2O (1), [Fe(H2O)2(ttmb)2](BF4)2·4H2O (2), [Fe(ttmb)2(NCS)2] (3), were synthesized with the linker 1,3,5-tris(1H-1,2,4-triazol-1-yl)methyl)benzene (ttmb). The single-crystal structures show that all three compounds form a double chain structure with the adjacent iron atoms being bridged by two ttmb linkers. The iron(II) ions are octahedrally surrounded by four N4 donor atom from the 1,2,4-triazol-1-yl groups of four different ttmb linkers which form an equatorial plane and two trans-coordinated aqua ligands in 1 and 2 or isothiocyanato ligands in 3 in the axial positions. In view of the neutral bridging ttmb linker, there is a counter-anion in all structures; uncoordinated ClO4– and BF4–in 1 and 2 or coordinated NCS–in 3. Compounds 1 and 2 are isostructural. Interestingly, the ttmb linker only utilizes two of its three potentially coordinating triazole groups. All iron(II) coordination networks are colorless or have a light-yellow color, being indicative of the high-spin state.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) is a commonly used technique for analyzing large biomolecules. However, the utilization of organic matrices limits the small-molecule analysis because of the interferences in the low-mass region and reproducibility issues. To overcome these limitations, a surface-assisted laser desorption/ionization (SALDI), which utilizes nanostructured metallic surfaces, has been developed. Herein, a novel approach for SALDI–MS was proposed using nanoengineered gold shell with nanogaps on the silica core (SiO2@Au NGS), which is an emerging material due to its excellent heat-generating capabilities. The gold shell thickness was controlled by adjusting the concentration of gold precursor for the growth of gold nanoparticles. SALDI-MS measurements were performed on a layer formed by drop-casting a mixture of SiO2@Au NGS and analytes. At the optimized process, the gold shell thickness was observed to be 17.2 nm, which showed the highest absorbance. The ion desorption efficiency was confirmed with a survival yield upon fragmentation. Based on the enhanced SALDI capability, SiO2@Au NGS was utilized to detect various small molecules including amino acids, sugars, and flavonoids. The limits of detection, reproducibility, and salt tolerance of SiO2@Au NGS demonstrate its potential as an effective and reliable SALDI material for small-molecule analyses.

Cervical carcinogenesis is the leading cause of cancer related death in women and the role of high-risk human papillomavirus (HR-HPV) as a possible risk factor in the development of this cancer is well recognised. Despite the availability of multi-therapeutic approaches, there is still a major concern regarding the prevention of metastatic dissemination and excessive tissue injuries. Therefore, it is imperative to develop a safer and more efficient treatment modality. Ficus Carica, a natural plant, has shown potential therapeutic properties through its fruit latex when applied to HPV-positive cervical cancer cell lines. However, the mechanisms of action of Ficus Carica (fig) latex are not well understood. This study aims to provide a deeper insight into the biological activities of fig latex on human cervical cancer cell lines expressing high-risk HPV types 16 and 18. The data obtained from this study reveals that fig latex influences the expression of genes in-volved in "Class I MHC-mediated antigen presentation" as well as "Antigen processing: Ubiquitination and Proteasome degradation." These genes play a crucial role in host immune surveillance and the resolution of infection. Findings from this study suggest that fig latex may enhance T cell responses against oncogenic HPV, which could be beneficial for the clearance of early-stage cancer.

Detecting suicidal ideation in adults with major depression is crucial for timely intervention and prevention of self-harm. As suicide is influenced by various biological, socio-cultural and psychological factors, traditional screening methods have accuracy and efficiency limitations. In certain cultures, societal stigma and marginalization can compel individuals with depression to conceal their suffering. Such individuals often turn to online social media platforms and share their experiences with peers under the protection of anonymity. Our research explored the potential of machine learning detection of suicidal ideation among Romanian adults with major depression that contributed to a web-based depression support forum. A trained algorithm (C4.5 decision tree) analyzed 125 posts fed to on a free access online support forum over 5 years (2014 – 2018) and classified them based on suicidal ideation content. 32 texts (25%) were identified as having a high probability of suicidal ideation content. 65% of the authors were male, with a mean age of 36.7±10.3 years and an average duration of illness of 3.4±1.4 years. Texts indicating positive suicidal ideation were generally shorter and elicited more general responses but fewer professional responses compared to those without suicidal ideation content. The study's main limitations include the relatively small number of classified texts, the absence of prospective information and the lack of qualitative evaluation of the excerpts' content. As socio-demographic and linguistic actuarial results were comparable to data reported by real life studies, we may consider basic text mining techniques as a screening tool that is able to detect suicidal ideation in texts written in unstructured Romanian language.

(1) Background: Metastasis is a complex process in which the primary cancer cells spread to a distant organ or organs, creating a secondary tumour location, which in many patients leads to treatment failure and death. The aim of the present study was to assess the association of endothelial markers (i.e., sP-selectin, sE-selectin and von Willebrand factor) with the leptin-to-adiponectin ratio (LAR) and to perform an analysis of the predictive value on the survival of patients with luminal A and B invasive breast cancer (IBrC). (2) Methods: The trial included 70 previously untreated women with a median age of 54.5 years and a median tumour size of 1.5 cm. The concentrations of pre- and post-treatment endothelial markers, leptin, and adiponectin were evaluated with specific ELISA kits. The median duration of follow-up was 68.5 months (interquartile range (IQR) = 59–72 months) with a recurrence rate of 15.71%. (3) Results: Regardless of the treatment pattern, endothelial marker concentrations and the LAR increased after treatment. The follow-up showed a significantly higher relapse rate in patients with IBrC who had higher pre-treatment sP-selectin and post-treatment LAR levels. A post-treatment LAR of 0.83 ng/mL with a sensitivity of 88.9% and specificity of 57.9% was established as the optimal cut-off value for distinguishing patients with or without disease recurrence. Additionally, a higher risk of breast cancer relapse was associated with a lower post-treatment sP-selectin concentration. (4) Conclusions: Our results showed mainly that pre-treatment sP-selectin levels and post-treatment LAR may have a value as prognostic indicators and may contribute to predicting the future outcome in patients with early-stage IBrC.

Desertification is a global environmental and socio-economical issue threatening humanity's survival and development. The Shiyang River Basin ecosystem is vulnerable and prone to desertification. In addition, establishing the quantitative analysis of desertification driving factors and understanding their relative contribution, separately or combined, is still an unresolved problem. The present study applied geographic information system (GIS) techniques and a geographic detector model to quantify desertification spatial extent and driving mechanisms. This research utilized Fractional Vegetation Cover (FVC) to elucidate desertification spatial heterogeneity. The 30 years Coefficient of Variation (CV) of the Normalized Difference Vegetation Index (NDVI) was a dependent variable and indicator of ecosystem terrestrial conditions; Elevation, near-surface air temperature, precipitation, wind velocity, land cover change, soil salinity, road buffers, waterway buffers, and soil types were independent variables. The results showed that 89.41% of the total area is under desertification risk, where 20.99% is extremely desertified, 34.45% is severely desertified, 12.05% is moderately, and 21.92% is slightly desertified. The results from the Geodetector model showed that Power Determinant (PD) values ranged between 0.004 and 0.270. Elevation and soil types had the highest contributing factors with PD values of 0.270 and 0.227, whereas precipitation, soil salinity, the buffer of the waterway, and wind velocity played a moderate role with PD values of 0.146, 0.117, 0.107, and 0.071. Near-surface air temperature, road buffer, and land cover dynamics exhibited lower impact with PD values of 0.028, 0.013, and 0.004. In most cases, investigating the interaction between driving factors resulted in a mutual or non-linear enhancement. There was an apparent linear and mutual enhancement between elevation and soil salinity, precipitation, and soil types with values of 0.3513, 0.3232, and 0.3204, respectively. In addition, there was a mutual enhancement between soil salinity and soil types with a value of 0.2962. On the other hand, a non-linear enhancement was observed between Elevation and near-surface air temperature (0.3116), Elevation and Land cover dynamics (0.2759), soil types and near-surface air temperature (0.2687), land cover dynamics and soil types (0.234), precipitation and near-surface air temperature (0.2248), precipitation and wind velocity (0.2248), and between land cover dynamics and precipitation (0.223). This research revealed irrefutable evidence that environmental factors might be the primary drivers of ecosystem disturbance, provided the basis for the environmental footprint of desertification mechanism, and might be a cornerstone for future policy on ecological restoration sustainability in the Shiyang River Basin.

Digitalisation is one of the European Union's priorities. The European Parliament is shaping and helping to shape new legislation in this area. Digitisation should also help in the transition to a greener economy and in achieving climate neutrality. E-government is one area of digitisation that has been under way for several years in European countries. In this paper, we have focused on identifying different indices that are aimed at measuring digitalization or e-Government. The results of the analysis showed that there are several indices that focus on this area within the EU, such as EGDI, EPI, LOSI, DGI, e-Government benchmark, Eurostat - internet use, GII, DSGI, Going Digital toolkit and DESI. Subsequently, the index areas to be used in the DEA method to measure the effectiveness of e-Government related inputs and outputs within the EU were identified. As can be seen from the analysis, the DEA method has various uses. In order to be able to use the method properly it was necessary to select the most appropriate parameter and to verify their suitability by means of correlation analysis. Among the input and output indices were chosen Internet usage, DSGI, GII, e-Government benchmark, Interaction with public administration online. From the analysis 3 inputs and 3 outputs were used. After implementing the correlation, it can be said that the values between the selected sub-variables are suitable for DEA analysis. Two models were chosen for the calculation, namely CCR and BCC model. CCR model evaluated 10 states as efficient and BCC model evaluated 13 states as efficient. In addition, in the close analysis, we have taken a closer look at the CCR model's inference. Countries such as Denmark, Finland, Estonia, Malta, Portugal, etc. were efficient outliers. When comparing the regions within the EU, we can conclude that the countries of Northern Europe are the most efficient in the field of digitalization (e-Government). As many as 4 countries out of 7 are efficient. In a future study it would be useful to use the SBM model and try to measure the impact of digitalization on selected areas such as economy, society, environment, etc.

This article investigated the Automatic Generation Control(AGC) of multi-area multi-source interconnected systems with hydropower plants, thermal power plants, and wind energy. Adaptive Neuro-fuzzy controller integrated with the cascaded proportional-integral-derivative with filter (PIDF-PIDF) is a new cascaded controller (ANF-PIDF-PIDF) that has been presented as a secondary controller for applied hybrid power systems. The recent Skill Optimization Algorithm (SOA) is employed to optimize PIDF- PIDF controller parameter gains and the Adaptive Neuro-Fuzzy controller's inputs and output scaling factors. SOA is used to update the controller parameters with integral square error (ISE) employed as the objective function. A 1% step load disturbance was considered simultaneously in all three areas. The controller's performance is evaluated and compared with and without considering the effects of wind energy sources and non-linearity for ANF-PIDF-PIDF, PIDF-PIDF, and PIDF and it was determined that the ANF-PIDF-PIDF was the most efficient. The dynamic system performance is also compared with parallel high voltage direct current (HVDC) tie-lines. The investigation clearly shows that incorporating HVDC tie-line with multi-area, multi-source provides better dynamic performance in maximum amplitude, oscillation, and settling time. Additionally, sensitivity analysis is done and the optimum controller gains does not need to be reset to uncertain values in system loading conditions. All simulation results were evaluated using MATLAB 2016b.

Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceded safe levels at 64 sites. We assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in Escherichia coli. Methods Spearman’s regression was used to assess the country-level association between the national prevalence of fluoroquinolone resistance in E. coli and the median ciprofloxacin concentration in the countries rivers. Results The prevalence of fluoroquinolone resistance in E. coli was positively correlated with the concentration of ciprofloxacin in rivers (ρ=0.36; P=0.011; N=48). Conclusions Steps to reducing the concentrations of fluoroquinolones in rivers may help prevent the emergence of resistance in E. coli and other bacterial species.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

While Europe was beginning to deal with the resurgence of COVID-19 due to the Delta variant, the European football championship took place, June 11 - July 11, 2021. We studied the inversion in the decrease/increase rate of new SARS-COV-2 infections in the countries of the tournament, investigating the hypothesis of an association. Using a Bayesian piecewise regression with a Poisson Generalized Linear Model, we looked for a changepoint in the timeseries of the new SARS-COV-2 cases of each country, expecting it to appear not later than two to three weeks after the date of their first match. The two slopes, before and after the changepoint, were used to discuss the reversal from a decreasing to an increasing rate of the infections. For 17 out of 22 countries (77%) the changepoint came on average 14.97 days after their first match [95% CI 12.29 to 17.47]. For all those 17 countries, the changepoint coincides with an inversion from a decreasing to an increasing rate of the infections. Before the changepoint, the new cases were decreasing, halving on average every 18.07 days [95% CI 11.81 to 29.42]. After the changepoint, the cases begin to increase, doubling every 29.10 days [95% CI 14.12 to 49.78]. This inversion in the SARS-COV-2 case rate, happened during the tournament, provides evidence in favor of a relationship

Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Endemic freshwater sponges (Demosponges, Lubomirskiidae) dominate in Lake Baikal and are multicellular filter-feeding animals represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of the L. baicalensis have been an urgent problem of Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria in microbiomes of diseased sponges of the families Flavobacteriaceae and Oxalobacteraceae were dominant. Both species are opportunistic pathogens common for freshwater ecosystems. The aim of our study is to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. The first one attacks the other cells using type VI secretion system, suppress gram-positive bacteria with violacein pigment and regulate its own activity via quorum sensing. It makes the floc and strong biofilm by exopolysaccharide biosynthesis and PEP‐CTERM proteins expression. The second one utilizes the fragments of cell walls produced of polysaccharides. Named two strains have noticeable difference in carbohydrates acquisition. We described the possible way of joint occupation of ecological niche into freshwater sponge microbial community. This study expands understanding about symbiotic relationship of microorganisms with freshwater Baikal sponges.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

Fibre reinforced cementitious materials (FRC) have become an attractive alternative for structural applications. Among such FRC, steel and polyolefin fibre reinforced concrete and glass fibre reinforced concrete are the most used ones. However, in order to exploit the properties of such materials structural designers need constitutive relations that reproduce FRC fracture behaviour accurately. This contribution analyses the suitability of multilinear softening functions combined with a cohesive crack approach for reproducing the fracture behaviour of the FRC previously mentioned. The implementation performed accurately simulates the fracture behaviour while being versatile, robust and efficient from a numerical point of view.

Shale gas reservoirs (SGR) are important replacements for conventional energy resources and have been widely exploited by hydraulic fracturing technologies. On the one hand, due to the inherent ultra-low permeability and porosity, there is stress sensitivity in the reservoirs generally. On the other hand, hydraulic fractures and the stimulated reservoir volume (SRV) generated by the massive hydraulic fracturing operation have contrast properties with the original reservoirs. These two phenomena bring huge challenges in SGR transient pressure analysis. Although some works in the literatures have been done on the transient pressure analysis of multi-fractured horizontal wells in SGR, unfortunately, none of them has taken the stress sensitivity and spatially varying permeability of SRV zone into consideration simultaneously. To fill this gap, this paper first idealizes the SGR to be four linear composite regions. What’s more, SRV zone is further divided into sub-sections on the basis of non-uniform distribution of proppant within SRV zone which easily yields spatially varying permeability away from the main hydraulic fracture. The stress sensitivity is characterized by the varying permeability depended on the pore pressure. By means of perturbation transformation and Laplace transformation, an analytical multi-linear flow model (MLFM) is obtained and validated by the comparison with the previous model. On the basis of our model, the flow regimes are identified and the sensitivity analysis of critical parameters are conducted to further understand the transient pressure behaviors. The research results provided by this work are of significance for well test interpretation and production performance analysis of SGR.

A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the evaluation of OTS167 pharmacokinetics in mouse serum. SN-38 was optimized to be selected as the internal standard. Chromatographic separation was performed on a BDS Hypersil C18 column (100 x 2.1 mm, 5 µm) using gradient elution with mobile phase solvent A as water containing 0.1% formic acid and solvent B as acetonitrile containing 0.1% formic acid. The analysis was carried out using multiple reaction monitoring (MRM) with a triple-quadrupole mass spectrometer operated in the positive electrospray ionization mode. Mass transitions of 487.2 > 348.0 and 393.2 > 349.2 were monitored for OTS167 and SN-38 respectively. The standard calibration curve demonstrated high linearity at a range of 5-1000 ng/mL, with a coefficient of determination (r2) ≥ 0.996. The accuracy for OTS167 ranged from 92.3% to 102.2% and the precision was ≤ 12.7%. Recovery was consistent at about 83% to 89%. No significant matrix effect was observed. This method was successfully applied to monitor the pharmacokinetic profiles in mice over 24 h after ingestion of 5 mg/kg of OTS167. Maximum serum concentrations (3197 ng/mL) of OTS167 was observed at 1.67 hour after OTS167 ingestion via garage at 5 mg/kg and area under the curve (AUC) was 28579 h*ng/mL, suggesting that OTS167 can be quickly absorbed after oral administration.

We use a regional scale photochemical transport model to investigate the surface concentrations and column integrated amounts of ozone (O3) and nitrogen dioxide (NO2) during a pollution event that occurred in the St. Louis metropolitan region in 2012. These trace gases will be two of the primary constituents that will be measured by TEMPO (Tropospheric Emissions: Monitoring of Pollution), an instrument on a geostationary platform, which will result in a dataset that has hourly temporal resolution during the daytime and ~4 km spatial resolution. Although air quality managers are most concerned with surface concentrations, satellite measurements provide a quantity that reflects a column amount, which may or may not be directly relatable to what is measured at the surface. Our model results provide reasonably good agreement with observed surface O3 concentrations (correlation coefficients ranging from 0.69 to 0.87 at each of the nine monitoring stations in the St. Louis region), which is the only trace gas dataset that can be used for verification. The model shows that a plume of O3 extends downwind from St. Louis and contains an integrated amount of ozone of ~ 16 Dobson Units (DU; 1 DU = 2.69 x 1016 molecules cm-2), an amount lower than what was observed during two massive pollution episodes in the 1980s. Based on the smaller isolatable emissions coming from St. Louis, this quantity is not unreasonable, but may also reflect the reduction of photochemical ozone production due to the implementation of emission controls that have gone into effect since the 1980s.

Background: This study aimed to investigate the effects of intradialytic concurrent (resistance-endurance) training combined with melatonin (MEL) supplementation on oxidative stress, inflammation, and cellular damage in hemodialysis (HD) patients. Methods: Thirty-two hemodialysis (HD) patients were randomly assigned to three groups: Exercise (EX)-MEL, EX-Placebo (PLA), and Control (C)-PLA. Participants in the EX-MEL and EX-PLA groups underwent 12 weeks of concurrent training. Before nocturnal sleep, they ingested either 3 mg of MEL (EX-MEL) or a placebo (EX-PLA and C-PLA). Blood samples were collected at baseline and after 12 weeks of intervention to assess lipid peroxidation [malondialdehyde (MDA)], antioxidant biomarkers [ferric reducing antioxidant power (FRAP), reduced glutathione (GSH), total thiol (THIOL)], total bilirubin (TBIL), uric acid (UA), biomarkers of muscle and liver damage [aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), creatine kinase (CK), lactate dehydrogenase (LDH), Gamma-glutamyltransferase (Gamma-GT)], and inflammation [C-reactive protein (CRP)]. Results: EX-MEL demonstrated a decrease of MDA (p

Ischemic stroke is a leading cause of mortality worldwide, and intravenous thrombo-lysis, while improving functional outcomes, still leaves a significant mortality rate. This study aimed to investigate the clinical and pathological data of thrombolysed stroke patients who subsequently died and underwent autopsy, focusing on hemorrhagic transformation (HT). Over a 10-year period, 1426 acute ischemic stroke patients re-ceived thrombolysis at our center, with an in-hospital mortality rate of 11.7%. Autop-sies were performed on 98 of the 167 deceased patients. HT was found in 47% of these cases, only less than half occurring within a day of thrombolysis. Significant inde-pendent predictors of HT included higher lactate dehydrogenase (LD) levels and higher INR values at admission. HT directly caused death in 30% of cases, often through herniation, while other complications (pulmonary embolism, pneumonia) were also common. These findings underscore the importance of postmortem investi-gations to accurately determine the incidence of HT and contributing factors. Our data indicate that in the vast majority of HT cases, the role of contributing factors other than rt-PA may be important. Of the routinely assessed clinical and laboratory parameters at admission only LD and INR were found to be independent predictors of HT in the autopsied studied cohort.

This cross-sectional, analytical, and observational study aimed to investigate the relationship between Visceral Adiposity Index (VAI) and anthropometric, biochemical, and insulin resistance (IR) parameters in Brazilians at risk of CVD. Biochemical parameters and anthropometric measurements were evaluated. The Pearson test was used to assess the correlation between VAI and anthropometric, biochemical, and IR parameters, with a predefined significance level of 5%. The analyzed sample consisted of 88 men and 72 women, with an average age of 58.78±13.48. VAI revealed noteworthy and positive correlations with all anthropometric parameters assessed (p&lt;0.0001). Furthermore, significant positive associations were noted between VAI and total cholesterol in women (p=0.0064), glycemia in men (p=0.0105), and LDL-c (p&lt;0.01) and triglycerides in both genders (p˂0.0001). A significant negative association was observed between VAI and HDL-c in both genders (p&lt;0.0001). Notably, the correlation between VAI and total cholesterol in men, glycemia in women, and CRP in both genders was not found to be significant. However, a significant relationship between VAI and IR parameters was observed in both sexes (p&lt;0.05). The results obtained from our study suggest that VAI functions as a simple and non-intrusive instrument, demonstrating significant effectiveness in identifying metabolic changes primarily associated with adipose tissue dysfunction, particularly dyslipidemia.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

This exploratory study investigates the role of wearable technologies in fostering emotional connections between human brands and customers. Given the rapid growth of the wearable technology market and the increasing importance of emotional connections in marketing, this research aims to uncover the potential of these technologies in strengthening the affective bond between brands and consumers. The mixed-method approach included semi-structured in-depth interviews with 25 marketing experts and an online survey of 300 consumers. Data analysis was conducted using thematic coding and statistical tests including Pearson correlation and multiple regression. Results indicated that wearable technologies can enhance emotional connections through personalized interactions (r=0.72, p<0.001), creating a sense of proximity (β=0.65, p<0.01), and facilitating two-way communications (β=0.58, p<0.01). These findings offer new perspectives for marketing strategies and customer relationship management in the digital age, highlighting the potential of wearable technologies as a powerful tool for building and maintaining emotional bonds between human brands and their audiences. The study contributes to the growing body of literature on technology-mediated brand relationships and provides practical implications for marketers seeking to leverage wearable technologies in their brand communication strategies.

This study, based on proactive motivation theory, explores the relationship between perceived overqualification, digital leadership, and constructive deviant behavior, as well as generational differences. Using data collected in two waves from 596 employees, the results show that perceived overqualification positively influences constructive deviant behavior, and digital leadership enhances this effect. Employees born in the 1980s are most influenced by both factors, followed by those born in the 1990s, where the effect of digital leadership is less significant. The study suggests that effectively utilizing digital leadership and recognizing generational differences in perceived overqualification can help organizations better manage overqualified talent, improving employee satisfaction and productivity.

The pH dependence of the free energy level of the flash induced primary charge pair P+IA– was determined by combination of the results from indirect charge recombination of P+QA– and from delayed fluorescence of the excited dimer (P*) in reaction center of photosynthetic bacterium Rhodobacter sphaeroides where the native ubiquinone at the primary quinone binding site QA was replaced by low potential anthraquinone derivatives. The following observations were made: 1) The free energy state of P+IA– was pH independent below pH 10 (–370 ± 10 meV relative to that of the excited dimer P*) and showed remarkable decrease (about 20 meV/pH unit) above pH 10. A not insignificant part of the dielectric relaxation of the P+IA– charge pair (about 120 meV) should come from protonation related changes. 2) The single exponential decay character of the kinetics proves that the protonated/unprotonated P+IA– and P+QA– states are in equilibria and the rate constants of protonation konH +koffH is much larger than that of the charge back reaction kback ~103 s-1. 3) Highly similar pH profiles were measured for the free energy states of P+QA– and P+IA–, indicating that the same acidic cluster around QB should response to both anionic species. This was supported by model calculations based on anticooperative proton distribution in the cluster with key residues of GluL212, AspL213, AspM17 and GluH173 and on effect of polarization of the aqueous phase on the electrostatic interaction. The larger distance of IA– from the cluster (25.2 Å) than that of QA‒ (14.5 Å) is compensated by smaller effective dielectric constant (6.5 ± 0.5 and 10.0 ± 0.5, respectively). 4) The P* → P+QA− and IA‒QA → IAQA− electron transfers are enthalpy driven reactions with exemption of very large (>60%) or negligible entropic contributions in cases of substitution by 2,3-dimethyl-AQ or 1-chloro-AQ, respectively. The possible structural consequences are discussed.

The field of interventional pulmonology has grown immensely and is increasingly recognized as a subspecialty. The new procedures introduced in the last decade pose unique challenges and the anesthesia providers need to readapt to their specific demands. In this review, we have discussed extensively the pathophysiology, technical aspects, preprocedural preparation, anesthetic management and postprocedural challenges of many new procedures such as navigational bronchoscopy, endobronchial valve deployment and bronchial thermoplasty. Majority of these procedures are performed under general anesthesia with an endotracheal tube. Total intravenous anesthesia with rocuronium as a muscle relaxant seems to the standard US practice. Easy availability and proven safety and efficacy of sugammadex as a reversal agent of rocuronium has decreased the need for high dose remifentanil as an agent to avoid muscle relaxants. Additional research is available with regards to the utility of nebulized lidocaine and is discussed. Finally, two newer drugs administered for conscious sedation (typically without the need of an anesthesia provider) are likely to gain popularity in the future. Remimazolam is a new short acting benzodiazepine with relatively faster offset of clinical effect. Dexmedetomidine, a selective adrenergic agonist, is increasingly employed in bronchoscopy as a sedative during bronchoscopic procedures.

No one can dismiss the fundamental role played by water in several important biochemical processes, including the folding of globular proteins. The so-called hydrophobic effect is the theoretical construction to rationalize how water molecules stabilize the folded state. However, over the years, analyses have been published that lead to the conclusion that water destabilizes the folded state. The aim of the present work is to state that the gain in translational entropy of water molecules (due to the decrease in water accessible surface area associated with folding) is the driving force of protein folding.