Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Background: The front-line treatment of advanced NeuroEndocrine Neoplasms (NENs) depends on clinical and pathological factors but there are no standard second-line therapies. Methods: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with second-line metronomic temozolomide, 75 mg/m2 per os “one week on/one week off”. Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. Results: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. Eleven patients presented with PS 1 and 15 with PS 2. The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from temozolomide start was 28.3 months. PS improved in 73% of patients. Conclusions: Metronomic temozolomide is a safe and active treatment for G2 and G3 NENs. Prospective and larger trials are needed to confirm these results.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

Buttonweed (Cotula coronopifolia) is native to South Africa but invasive in wetlands in Europe, North America, and Australasia, where it excludes native plants. Despite being dry-fruited, field studies suggest migratory waterbirds can disperse its seeds via gut passage (endozoochory), aiding its expansion. To explore the potential for endozoochory in different regions and habitats, we collected seeds from six populations in Spain, Sweden, and the UK. Germination was tested under different salinity levels (0, 5, 10, 15 g/L) and simulated gut passage treatments: scarification, acidification, or both. No germination occurred at 15 g/L. Higher salinity reduced and delayed germination, but full gut passage treatment increased germinability and accelerated germination. Scarification or acid treatment alone resulted in intermediate germination patterns. There were significant salinity x population and gut passage x population interactions on germinability. The acceleration effect of gut passage on germination was stronger at 5-10 g/L than at 0 g/L. This study highlights how migratory birds can facilitate the spread of alien plants introduced by humans. Non-classical endozoochory by waterbirds is an understudied mechanism for the long-distance dispersal of dry-fruited alien plants. Further research on C. coronopifolia, including population genetics, is necessary to understand dispersal mechanisms and facilitate management strategies.

Dietary factors are one of the risk factors that can impact the brain chemistry, which leads to mental distress. Based on our data mining approach, we found that mental distress in men is associated with eating unhealthy food. Our aim in this paper is to apply results from our big data analytics approach to inform system dynamics (SD) modeling to investigate the causal relationships between brain structures, nutrients from food and dietary supplements, and mental health. We perform descriptive analysis based on a large data set to estimate the SD modeling parameters. Finally, we calibrate the model towards a time series data collected for individuals on their dietary and distress patterns. The results reveal that bridging these different methodologies leads to further insights from the SD model and decreases the error of calibrated parameter values. Future research is needed to validate our initial results for investigating the relationship between mental distress and dietary intake.

Banana (Musa spp.) is an important crop to the economies of many developing countries. In the north of Argentina, a sub-tropical region, banana plants grow in a suboptimal environment that limits yield because only one harvest per year is achieved. The objective of this work was to characterize the agroecological aptitude of Formosa, Argentina, for banana production, through the behavior of three varieties of international use: Willians, Jafa and Gran Enano, evaluated during five consecutive campaigns. The three-way data analysis technique called Multiple Factor Analysis (MFA) was used for evaluating varieties’ performances across cycles of production. The results allowed inferring the existence of genotype x environment (GEI) interaction, corroborated by two-way factorial ANOVA. In order to determine how this suboptimal environment affects the development of each genotype of this perennial crop, Dual Multiple Factor Analysis (DMFA) was applied to jointly analyze the correlation structure among traits contributing to the performance of each variety at each campaign. The correlation structures between variables were different in each population and varied among campaigns. All traits showed a great variation across years and genotypes, the fruit peel thickness being the most discrepant throughout the campaigns. However, Formosa appeared as a promising subtropical agroecological environment to produce banana because varieties’ performances were acceptable for large scale production systems. In addition to evaluating the adequate aptitude for cultivating banana in Formosa considering the significant effect of GEI, this research makes a methodological contribution by proposing the use of three-way data analysis MFA and DMFA in Agronomy Science.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Based on 2010, 2013 and 2015 CGSS data, the impact of Internet use and social capital on the income gap among farmers in the past five years is assessed at three time points using the OLS method and a quantile regression method. The study finds that (1) the income gap among farmers increases continuously in the five-year period, while Internet use plays a positive impact on farmers’ income growth in all five quartiles; the coefficient differences are all significantly negative, indicating that Internet use plays a positive role in alleviating the income gap between high-income and low-income farmer subgroups, and (2) social capital plays a positive role in moderating the income gap among farmers and that Internet use by farmers expands the boundary of social capital, which in turn increases the income level of and alleviates the income gap among farmers.

Capacity Expansion Models (CEMs) are optimization models used for long-term energy planning on national to continental scale. They are typically computationally demanding, thus in need of simplification, where one such simplification is to reduce the temporal representation. This paper investigates how using representative periods to reduce the temporal representation in CEMs distorts results compared to a benchmark model of a full chronological year. The test model is a generic CEM applied to Europe, equipped with a novel formulation for storage in model versions with reduced temporal representation. We test the performance of reduced models at penetration levels of wind and solar of 90%. Three measures for accuracy are used: (i) system cost, (ii) total capacity mix and (iii) regional capacity. We find that: (i) the system cost is well represented (~5% deviation from benchmark) with as few as ten representative days, (ii) the capacity mix is in general fairly well (~20% deviation) represented with 50 or more representative days, and (iii) the regional capacity mix displays large deviations (>50%) from benchmark for as many as 250 representative days. We conclude that modelers should be aware of the error margins when presenting results on these three aspects.

Over the last decades, the energy market around the world has reshaped due to accommodating the high penetration of renewable energy resources. Although renewable energy sources have brought various benefits, including low operation cost of wind and solar PV power plants, and reducing the environmental risks associated with the conventional power resources, they have imposed a wide range of difficulties in power system planning and operation. Naturally, classical optimal power flow (OPF) is a nonlinear problem. Integrating renewable energy resources with conventional thermal power generators escalates the difficulty of the OPF problem due to the uncertain and intermittent nature of these resources. To address the complexity associated with the process of the integration of renewable energy resources into the classical electric power systems, two probability distribution functions (Weibull and lognormal) are used to forecast the voltaic power output of wind and solar photovoltaic, respectively. Optimal power flow, including renewable energy, is formulated as a single-objective and multi-objective problem in which many objective functions are considered, such as minimizing the fuel cost, emission, real power loss, and voltage deviation. Real power generation, bus voltage, load tap changers ratios, and shunt compensators values are optimized under various power systems’ constraints. This paper aims to solve the OPF problem and examines the effect of renewable energy resources on the above-mentioned objective functions. A combined model of wind integrated IEEE 30-bus system, solar PV integrated IEEE 30-bus system, and hybrid wind and solar PV integrated IEEE 30-bus system are performed using the equilibrium optimizer technique (EO) and other five heuristic search methods. A comparison of simulation and statistical results of EO with other optimization techniques showed that EO is more effective and superior.

Over the last decades, the energy market around the world has reshaped due to accommodating the high penetration of renewable energy resources. Although renewable energy sources have brought various benefits, including low operation cost of wind and solar PV power plants, and reducing the environmental risks associated with the conventional power resources, they have imposed a wide range of difficulties in power system planning and operation. Naturally, classical optimal power flow (OPF) is a nonlinear problem. Integrating renewable energy resources with conventional thermal power generators escalates the difficulty of the OPF problem due to the uncertain and intermittent nature of these resources. To address the complexity associated with the process of the integration of renewable energy resources into the classical electric power systems, two probability distribution functions (Weibull and lognormal) are used to forecast the voltaic power output of wind and solar photovoltaic, respectively. Optimal power flow, including renewable energy, is formulated as a single-objective and multi-objective problem in which many objective functions are considered, such as minimizing the fuel cost, emission, real power loss, and voltage deviation. Real power generation, bus 13 voltage, load tap changers ratios, and shunt compensators values are optimized under various power systems’ 14 constraints. This paper aims to solve the OPF problem and examines the effect of renewable energy resources 15 on the above-mentioned objective functions. A combined model of wind integrated IEEE 30-bus system, solar 16 PV integrated IEEE 30-bus system, and hybrid wind and solar PV integrated IEEE 30-bus system are performed 17 using the equilibrium optimizer technique (EO) and other five heuristic search methods. A comparison of 18 simulation and statistical results of EO with other optimization techniques showed that EO is more effective 19 and superior.

With an increased interest in applications that require a clean background image, such as video surveillance, object tracking, street view imaging and location-based services on web-based maps, multiple algorithms have been developed to reconstruct a background image from cluttered scenes. Traditionally, statistical measures and existing image quality techniques have been applied for evaluating the quality of the reconstructed background images. Though these quality assessment methods have been widely used in the past, their performance in evaluating the perceived quality of the reconstructed background image has not been verified. In this work, we discuss the shortcomings in existing metrics and propose a full reference Reconstructed Background image Quality Index (RBQI) that combines color and structural information at multiple scales using a probability summation model to predict the perceived quality in the reconstructed background image given a reference image. To compare the performance of the proposed quality index with existing image quality assessment measures, we construct two different datasets consisting of reconstructed background images and corresponding subjective scores. The quality assessment measures are evaluated by correlating their objective scores with human subjective ratings. The correlation results show that the proposed RBQI outperforms all the existing approaches. Additionally, the constructed datasets and the corresponding subjective scores provide a benchmark to evaluate the performance of future metrics that are developed to evaluate the perceived quality of reconstructed background images.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Forest resources are renewable,rational exploitation and utilization of forest resources are not only conducive to sustainable development of population, but also can obtain higher economic benefits. Based on actual timber harvesting problems,a combined harvesting model of timber and non-timber with nonlinear harvesting term was established.Firstly, using the qualitative theory of ordinary differential equations, the dynamic behavior of the model is studied, and the existence and stability of the equilibrium point of the model are proved .Secondly, the optimal control solution is obtained by using the optimal control theory.Finally, the optimal harvesting strategy of timber and non-timber products is given based on the numerical simulation results, which provides a certain theoretical basis for the sustainable development of forestry ecological economy.

The receptor-type protein tyrosine phosphatases (RPTPs) are involved in a wide variety of physiological functions which are mediated via their diverse extracellular regions. They play key roles in cell-cell contacts, bind various ligands and are regulated by dimerization and other processes. Depending on the subgroup they have been described as everything from ‘rigid rods’ to ‘floppy tentacles’. Here we review current experimental structural knowledge on the extracellular region of RPTPs and draw on AlphaFold structural predictions to provide further insights into structure and function of these cellular signalling molecules.

Macrophages as a source and target of GDF-15

This study examines whether information about the winners of the Sustainability Reporting Award (SRA) contributes to the usefulness of the information in the financial statements. This study used a sample consisting of 110 winners of SRA (SRA firms) and 110 companies that did not receive SRA (non-SRA firms) from 2008 to 2016. The study found that earnings per share (EPS), book value per share (BVPS), and earnings per share change (EPSC) are value relevant information. Results of comparison between SRA firms and non-SRA fimrs, this study found that EPS positive association with stock price and with returns for SRA firms is higher than that for non-SRA firms. Findings of this study also show that, value relevance of BVPS for non-SRA firms is higher than that for SRA firms. When mesures of Price and BVPS are transformed into natural logarithm, the value relevance of BVPS for SRA firms is higher than that for non-SRA firms. Thus, the results are sensitive to measures of the variables. The findings of this study indicate that information about the winners of SRA contributes to the usefulness of financial statements.

The meridian line is a basic instrument for positional astronomy, it was used to study the motion of Sun, Moon, planets and the position of stars by measuring position and time of their passage through the meridian plane. The accuracy of such positions was dependent on precise theories of the atmospheric refraction (Cassini, 1655 and Laplace, 1825) and by the use of reference marks present originally on the meridian line, and now cancelled by the centuries. From October 27, 2018 the new pinhole of the meridian line in the Basilica of S. Maria degli Angeli in Rome (1702) is a circle 25 mm wide and 6.11 mm thick and its position is fixed, in order to perform a series of observations of astrometric quality, the IGEA campaign. The comparison of the observed positions of the meridian passages of the Sun, Southern and Northern limbs, with the ephemerides of Calsky.org and Stellarium 0.20.2 for the Sun are examined for the dates of the ingresses into the zodiacal signs, when the ecliptic longitude is exactly 0°/180° (Aries and Libra, spring and fall equinox), 30°/150° (Taurus, Virgo), 60°/120° (Gemini, Leo), 90° (Cancer), 330°/210° (Pisces, Scorpio), 300°/240° (Aquarius/Sagittarius), 270° (Capricorn). The former geometrical calibration of the marks present on the line, with a total station, is compared with another calibration done with a metal and laser meter. The first star on the floor of the Basilica representing the position of the Sun on August 20, 1702 when the pope Clement XI visited the meridian line, financed by him, has been calibrated with the solar image. The present pinhole is 4.4±0.1 mm South with respect to the original one of 1702.

Since the COVID-19 caused by SARS-CoV-2 break out in Wuhan China from Dec. 2019, it has spread to hundreds of countries up to now. Scientists from all over the world have paid tremendous efforts to research and try to control the disease. Previous studies suggested that some of the wild animals could be intermediate hosts between humans and origination of SARS-CoV-2, and some companion animals of humans can be infected by SARS-CoV-2, which raised our curiosity about cross-infection of SARS-CoV-2 between animals and humans. Thus, we select some kinds of animals that might have contact with humans to estimate the susceptibility to SARS-CoV-2 in different animals by evolutionary analysis of their receptors for SARS-CoV-2. The results show that some companion animals of the Felidae family like the cat has a higher infection possibility while the species of the Rodent family like the rat and mouse having close contact with humans show an opposite result, which consist with recent animal experiments and researches. These should raise concerns about cross-infection between human and companion animals or animals having close contact with humans which might turn animals into depositaries of the coronavirus even after control of SARS-CoV-2 spreading and cause second or more waves of infections after social reopening. Another side of our results stands by the opinion that bioinformatic analysis can be consistent with experiments in some respects so that we can prevent unnecessary sacrifice of laboratory animals in future experiments.

Colombia is noteworthy as a biodiversity hotspot, featuring an extraordinary number of en-demic orchids, birds, and butterflies. This exploratory study examines the perceptions of desti-nation image considering the cognitive and affective image in predicting behavioral intentions of ecotourists through symmetric data analysis. Using Partial Least Squares (PLS), the author(s) analyzed 64 survey responses collected of rural areas, including a new 15 statement scale spe-cialized on birdwatching. The findings support the reliability of the model, symmetric analysis presents the higher influence of emotions and affections in increasing intentions of recommen-dation, considering birdwatching as based on personal relationships. Additionally, the cognitive image for the birders despite representing destination attributes or sets of destination resources of a mental picture does not have the same impact on behavioral intentions. Therefore, manag-ers should develop positioning strategies based on the generation of emotions, because bird-watching tourists seek to have more emotional experiences.

Color image binarization plays a pivotal role in image preprocessing work, significantly impacting subsequent tasks, particularly in text recognition. This paper concentrates on Document Image Binarization (DIB), aiming to separate a image into foreground (text) and background (non-text content). Through a thorough analysis of conventional and deep learning-based approaches, we conclude that prevailing DIB methods leverage deep learning technology. Furthermore, we explore the receptive fields pre- and post-network training to underscore the Transformer model's advantages. Subsequently, we introduce a lightweight model based on the U-Net structure, enhanced with the Mobile ViT module to better capture global information features in document images. Given its adeptness at learning both local and global features, our proposed model exhibits superior performance on two standard datasets (DIBCO2012 and DIBCO2017) compared to state-of-the-art methods. Notably, our proposed DIB method presents a straightforward end-to-end model devoid of additional image preprocessing or post-processing. Moreover, its parameter count is less than a quarter of the HIP'23 model, which achives best results on three datasets(DIBCO2012, DIBCO2017 and DIBCO2018). Finally, two sets of ablation experiments were conducted to verify the effectiveness of the proposed binarization model.

In large-scale parallel computing and communication systems, an interconnect network structure is usually modeled as a graph, in which vertices and edges correspond to processors and communication links, respectively. In a graph, the vertices and edges are likely to fail, so we must think about the fault tolerance of a graph. Connectivity is an important parameter in the study of faulty tolerance for a graph. In this paper, we study a special class of connectivity: $m$-component connectivity, this is a natural generalization of the classical connectivity of graphs defined in terms of the minimum vertex-cut. Let $F$ is a vertex set of $G$ $(i.e, F\subseteq V(G))$, if the following conditions are satisfied, we say $F$ is a $m$-component cut: $(1)$ $G-F$ is disconnected; $(2)$ the number of components in $G-F$ is greater than or equal to $m$. In another word, the $m$-component connectivity $c\kappa_{m}(G)$ is defined as $min\{|F|~|~F\subseteq V(G)$ and $F$ is a $m$-component cut$\}$. Determining $m$-component connectivity is still unsolved in most interconnection networks even for small $m'$s. Leaf-sort graph is a special Cayley graph, it has many special properties that are different from other Cayley graphs. So we need to pay attention to some of it's special properties when we study it. In this paper, we can get the values: $c\kappa_{3}(CF_{n})=3n-6$ $(n$ is odd$)$ and $c\kappa_{3}(CF_{n})=3n-7$ $(n$ is even$)$ for $n\geq3$; $c\kappa_{4}(CF_{n})=\frac{9n-21}{2}$ $(n$ is odd$)$ and $c\kappa_{4}(CF_{n})=\frac{9n-24}{2}$ $(n$ is even$)$ for $n\geq4$; $c\kappa_{5}(CF_{n})=6n-16$ $(n$ is odd$)$ and $c\kappa_{5}(CF_{n})=6n-18$ $(n$ is even$)$ for $n\geq5$.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Reservoir computing is a machine learning method that uses the response of a dynamical system to a certain input in order to solve a task. As the training scheme only involves optimising the weights of the responses of the dynamical system, this method is particularly suited for hardware implementation. Furthermore, the inherent memory of dynamical systems which are suitable for use as reservoirs mean that this method has the potential to perform well on time series prediction tasks, as well as other tasks with time dependence. However, reservoir computing still requires extensive task dependent parameter optimisation in order to achieve good performance. We demonstrate that by including a time-delayed version of the input for various time series prediction tasks, good performance can be achieved with an unoptimised reservoir. Furthermore, we show that by including the appropriate time-delayed input, one unaltered reservoir can perform well on six different time series prediction tasks at a very low computational expense. Our approach is of particular relevance to hardware implemented reservoirs, as one does not necessarily have access to pertinent optimisation parameters in physical systems but the inclusion of an additional input is generally possible.

Scientists who hope to obtain a faculty position at a primarily undergraduate institution (PUI) need a distinct skill set and outlook on their future teaching and research career. To obtain a position at a PUI, candidates should 1) design a strategy for obtaining a faculty position that suits each individual’s career goals and aspirations, 2) prepare for the application process, on-campus interview, and contract negotiations, and 3) plan a strategy for the probationary period leading up to tenure and promotion. Given the different types of PUIs, candidates need to consider whether they seek a position that consists of all or mostly all teaching, or both teaching and research. Candidates should educate themselves on the expectations at PUI’s, including current thought, practice, and aspirations for science pedagogy, and gain teaching experience prior to seeking a suitable position. If the candidate’s goal is a position with both teaching and research, it is important to discuss with the current research mentor what projects the candidate can take with them to their new position. The candidate should also consider what types of projects will be successful with undergraduate student researchers in a PUI research environment Importantly, candidates should clearly demonstrate a commitment to diversity and inclusion in their teaching, research, and outreach, and application materials should demonstrate this. On interviews, candidates should be knowledgeable about the mission, values, and resources of the institution and how the candidate will contribute to that mission. Once hired, new faculty should discuss a formal or informal mentoring plan during the probationary period that includes peer evaluations on a regular basis, and maintain communication with the department chair or designated mentor regarding teaching, research, and service activities.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

This study analyzed the CO2 capture potential for Parque Natural Regional Serrania de las Quinchas buffer area in Colombia. For this purpose, multitemporal analysis for land covering for years 1989, 2000, 2006, 2011, 2017 and 2021 was made using the Normalized Difference Vegetation Index (NDVI), and Corine Land Cover (CLC) methodology. In the same way, Aboveground Biomass (AGB) was measured for representative parcels by measuring tree’s diameters and heights and applying the adequate allometric models; carbon content in soils was measured too. Results show that dense forest has grown since 1989 and the carbon stock in all the vegetation covers increased by 14,3% from 1989 until 2021, using literature data for tropical humid forests. If measured AGB values obtained in this study are used, the carbon stock average is 3 times this value. Measured carbon average content in AGB was 374,3 Ton C/Ha, well above the average for the content reported for humid tropical forests in Colombia; carbon content in soils was 897,19 Ton/Ha, 2,4 times that found in the AGB. In total, an average of 1271,49 Ton C/Ha (AGB+ soil) was found and a pattern of dense forest recovery was found, but in a more dispersed way than in the past. A very interesting potential for existing forests recovery was found for this area. Strategies for this include the development of sustainable practices, land use management, everything pursuing biodiversity preservation and the participation and leading of the local communities.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

Considering characteristics of high river density, special underlying surface in plain river network region, and municipal drainage system function, river network drainage unit model is proposed, which is defined as a region surrounded by main river or embankment. Flood storage variety and control projects regulation of small rivers in each unit is simulated. With drainage catchment as an object, according to its drainage capacity, simplified municipal drainage model was developed. Coupling river network drainage unit model, simplified municipal drainage model and 2D flood routing model, urban flood analysis model for plain tidal river network region was developed, which could be applied to analyzing flood from upstream river, storm surge and local rainfall. Demonstration research was carried out in Puxi flood protected area in Shanghai.

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer-leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively characterised cEVs by flow cytometry with special attention to the proportions of PS in chronic heart failure patients (cHF; n=119) and reference non-HF group (n=21). PS─-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS─-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in non-HF. We observed similar levels of PS+- and PS─-cEVs in non-HF subjects when analysing immune cell-derived EVs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+ and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+ and CD56+ were mainly PS─-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients as detected by a high shedding of cEVs. Despite PS+-cEVs and PS─-cEVs represent two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to PS content.

In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

This paper presents the results of a recent study that was conducted with a number of German municipalities/cities. Based on the obtained and briefly presented recommendations emerging from the study, the authors propose the concept of an Urban Data Space (UDS), which facilitates an eco-system for data exchange and added value creation thereby utilizing the various types of data within a smart city/municipality. Looking at an Urban Data Space from within a German context and considering the current situation and developments in German municipalities, this paper proposes a reasonable classification of urban data that allows to relate the various data types to legal aspects and to conduct solid considerations regarding technical implementation designs and decisions. Furthermore, the Urban Data Space is described/analyzed in detail, and relevant stakeholders are identified, as well as corresponding technical artifacts are introduced. The authors propose to setup Urban Data Spaces based on emerging standards from the area of ICT reference architectures for Smart Cities, such as DIN SPEC 91357 “Open Urban Platform” and EIP SCC. Thereby, the paper walks the reader through the construction of an UDS based on the above mentioned architectures and outlines all the goals, recommendations and potentials, which an Urban Data Space can reveal to a municipality/city.

We hypothesized that reticuloruminal temperature and pH, as well as cow activity, can be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows. Therefore, we aimed to detect the relationship between reticuloruminal temperature and pH, cow activity, and clinical mastitis in dairy cows. We randomly selected cows with clinical mastitis and clinical healthy cows (HG) out of 600 milking cows. We recorded the following parameters during the experiment: reticulorumen tem-perature (RR temp.), reticulorumen pH (RR pH), and cow activity. We used smaXtec boluses (smaXtec animal care technology®, Graz, Austria). In this investigation, reticulorumen data ob-tained seven days before diagnosis were compared to HG data from the same time period. CM cows were observed on the same days as the healthy cows. The healthy group’s RR pH was 7.32% higher than that of cows with CM. Reticulorumen temperature was also 1.25% higher in the CM group than in the control group. The healthy group had a higher average value for walking activity and was 17.37% higher than the CM group. The data of reticulorumen pH changes during 24 h showed that during the day, the pH changed from 5.53 to 5.83 in the CM group. By contrast, pH changed from 6.05 to 6.31 in the control group. The lowest reticulorumen pH in the CM group was detected on the third day before diagnosis. It was 15.76% lower than the highest reticulorumen pH detected on the sixth day before diagnosis. The lowest reticulorumen pH in CM cows was detected at 0 and 1 days before diagnosis. It was 1.45% lower than the highest reticulorumen pH detected on the second day before diagnosis. The lowest walking activity in the CM group was detected 0 days before diagnosis, 50.60% lower than on the fifth day before diagnosis. The lowest walking activity was detected 0 days before diagnosis, 39.57% lower than on the seventh day before diagnosis. In this study, we found that reticuloruminal temperature, reticuloruminal pH, and cow ac-tivity could be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

The chemically synthesized polymer polyacrylamide (HPAM) in conventional reservoirs has achieved excellent oil displacement, but its oil displacement is poor in extreme reservoir environments. To develop biopolymer oil flooding agent under extreme reservoir conditions, the viscosity increasing and rheological properties of three biopolymers, diutan gum, xanthan gum, and scleroglucan, were studied under extreme reservoir conditions (high salt, high temperature, strong acid, and alkali), and the effects of temperature, mineralization, pH, and other factors on their viscosities and long-term stability properties were analyzed and compared. The results showed that under the temperature of 90℃ and below, the three kinds of biopolymers had the best viscosity-increasing ability. The viscosity of the three kinds of biopolymers was 80.94, 11.57, and 59.83mPa·s, respectively, when the concentration was 1500mg/L and the salinity was 220g/L. At the shear rate of 250s-1,100℃~140℃, scleroglucan has the best viscosification. At 140℃, the solution viscosity is 19.74mPa·s, and the retention rate can reach 118.27%. The results of the long-term stability study showed that the solution viscosity of scleroglucan with mineralization level of 220 mg/L was 89.54% viscosity retention in 40 days, and the diutan gum could be stabilized for 10 days, and the viscosity was maintained at 90 mPa·s. All three biopolymers are highly acid and alkali-resistant, with viscosity variations of less than 15% in the pH3~10 range. Rheological tests have shown that both of them have better viscoelastic properties than xanthan gum due to the peculiar double-helix structure of xanthan gum and the rigid triple-helix structure of scleroglucan. Therefore, the two biopolymers, diutan gum, and scleroglucan have the potential for extreme reservoir oil displacement applications, and it is recommended to use diutan gum for oil displacement in reservoirs up to 90℃ and scleroglucan for oil displacement in reservoirs between 100℃ and 140℃.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants-small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

Background. Artificial Intelligence (AI) is an advanced technology for the latest 20 years. Machine learning (ML) and deep learning (DL) are the major innovations for AI, which has been applied for multiple fields. Ophthalmology has become to be one of the most significant disciplines for human healthcare. Methodology. This study utilizes methods of text mining and bibliometric analysis to explore applications of AI to ophthalmology. 179 related articles from Web of Science (WOS) and 96 papers from China National Knowledge Infrastructure (CNKI) are explored during the period of 2000 to 2021. A descriptive analysis of major trends, journal releasing, topic mapping and quotation relationships is implemented in this paper. Leading authors, journals, institutions, nations and references in the related research are identified. Results. Findings show that the application of AI technologies in ophthalmologic diagnosis with optical coherence tomography (OCT) fundus images is the core topic for this area’s studies, especially for diabetic retinopathy (DR), aged macular degeneration (AMD) and glaucoma. It is also be predicted as the core direction over the recent years. Besides, The USA, England and China is the most competitive countries in this scientific filed. Journals of Ophthalmology, Investigative Ophthalmology and Visual Science, Eye, Acta Ophthalmologica and Scientific Reports are the top five journal related to the research area. There is a significant difference between WOS and CNKI databases pertaining to the application of Artificial Intelligence (AI) to ophthalmology, especially for the historic development, topic mapping and discipline category. Finally, the potential academic value of interdisciplinary subject of “AI in Ophthalmology” and tradition Chinese medicine (TRM) is discussed. Limitations and suggestions for the future research is indicated at the end of this paper.

Background Obesity compromises the health of a woman's pregnancy and her newborn. Aim: To describe weight-gaining changes throughout pregnancy and evaluating outcomes for the mother and the baby. Methods A retrospective review of women who delivered singletons using Large Perinatal Registry. According to their BMI, patients were categorized into four categories: underweight, normal, overweight, and obese. Mode of delivery, gestational diabetes, hypertensive diseases, obstetric cholestasis, and postpartum hemorrhage were the main maternal outcome measures. The newborn outcome indicators were birth weight, NICU hospitalization, premature birth, and stillbirth. Results The study sample included 2,352 natives (25%) and 7,058 expatriates (75%). The majority of the sample (4726) were aged 20-29 years, 43.6% were aged 30-39 years, and 2.1% and 3.9% were aged 19 years and 40 years respectively. The incidence of hypertension, obstetric cholestasis, diabetes, postpartum hemorrhage, and cesarean section varied among the entire sample. In the underweight group, the incidence of CS was 15.7%, in the normal weight group (24.9%), in the overweight group (31.3%), and in the obese group (41%). Hypertensive disorders were 3 times more prevalent in obese women than in normal-weight women (2%), and 5.3% of obese women had PPH compared to 5. 6% of women of normal weight. The underweight groups gained the most weight during pregnancy, whereas the obese gained the least. Conclusions A significant proportion of pregnant women in our sample will become obese by the time of delivery. Obesity during pregnancy is associated with negative maternal and fetal outcomes.

Although there are extensive literature reports on the use of gold nanoparticle (AuNP) based homogeneous assays for detection of biomolecules, very few experimental description and procedures involving their preparation are described. In this study, AuNPs conjugated to Bovine Serum Albumin or Envelope protein from Dengue II were developed as a homogeneous immunoassay for antibody detection. We report here optimization of key parameters to prepare an immunoassay like conjugation protein concentration, centrifugation time, electrolyte addition and assay temperature. We determined that saturating protein concentrations improved AuNPs surface coverage and uniformity of the assay and addition of sodium chloride improved sensitivity of the antibody detection method and assay stability. Furthermore, we showed that dynamic light scattering can be used to monitor changes in gold nanoparticles in the preparation and detection steps. Additionally, numerical simulations of the plasmonic optical response of AuNPs were carried out to scan for size-dependent response of the AuNPs. The AuNPs homogeneous immunoassay developed was further used in the detection of antibodies in vitro to detect Dengue virus infection.

We developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. Near-infrared laser irradiation stimulated the generation of reactive oxygen species, causing short-term reactive molecular species and spatial-temporal restricted photodamage to the biological targets. The reactive molecular species and spatial-temporal restricted photodamage enhanced the release and uptake of chemotherapy drugs and increased the sensitivity to chemotherapy drugs in ovarian cancer cells. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. SN38/IR820-Lipo@FSH exhibited good drug-loading properties and the in vitro release was slow. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited good tumor-targeting ability and anti-ovarian cancer activity in vivo. The SN38/IR820-Lipo@FSH exhibited specific targeting to A2780 ovarian cancer cells. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24-h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.

Snow-covered regions are the main source of reflection of incident shortwave radiation (ISR) on Earth’s surface. The deposition of light-absorbing particles (LAPs) on these regions increases the capacity of snow to absorb ISR and decreases surface snow albedo (SSA), which intensifies the radiative forcing leading to accelerated snowmelt and modifications of the hydrologic cycle. In this work we investigate changes in SSA and radiative forcing (RF) induced by LAPs in the Upper Aconcagua River Basin (Chilean central Andes) using remote sensing satellite data (MODIS), in-situ spectral SSA measurements, and the ISR (Chilean Solar Explorer platform) during the austral-winter months (May to August) for the 2004-2016 period. To estimate the changes in SSA and RF, we define two spectral ranges: i) an enclosed range (Ecr) between 841-876 nm, which isolates effects of Black-Carbon, an important LAP derived from anthropogenic activities, and ii) a broadband range (Bbr) between 300-2500 nm. Our results show that percent variations in SSA in the Ecr are higher than in the Bbr, regardless of the total amount of radiation received, which may be attributed to the presence of LAPs as these particles have a greater impact on SSA at wavelengths in the Ecr band than in the Bbr band.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Abstract: A fertilisation experiment with aim to determine the effect of different potassium fertiliser rates and their interaction with nitrogen and phosphorus on field rotation productivity, potassium balance, fertiliser utilization and changes in content of potassium in soil was carried out in Lithuania between 1971 and 2020. The multi-factorial scheme with 45-treatment plots, where seven (including zero) rates of nitrogen, phosphorus and potassium fertilisers were studied. The experimental treatments during the study period included winter wheat, spring wheat, spring barley, sugar beet, spring rapeseed, annual and perennial grasses. It was found that potassium fertilisers was the most effective on agricultural crops when used in combination with other major plant nutrients – nitrogen and phosphorus. The balance of potassium (K2O) in soil, when nitrogen and phosphorus fertilisers were applied together, to compensate for potassium removal, when applying low nitrogen (N) 72 kg ha-1 and phosphorus (P2O5) 64 kg ha-1 fertiliser rates, 128 kg ha-1 of potassium fertilisers is required. When using high nitrogen 180 kg ha-1 and phosphorus 160 kg ha-1 fertiliser rates, 160 kg ha-1 of potassium is needed. The highest potassium uptake, reaching 51.6%, was achieved when plants had been fertilised with nitrogen 108 kg ha-1, phosphorus 96 kg ha-1, and potassium 96 kg ha-1. When fertilising with potassium fertilisers alone, the content of plant available K2O content in the soil increased, while fertilisation with nitrogen and phosphorus combined it’s decreased, except in the plots where the plants had been fertilised with potassium fertiliser at rates of 128 kg ha-1 and higher. Due to the influence of fertilizers, the amount of non-exchangeable potassium in the soil also increased, but relatively less compared to the amount of available potassium content.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

It has recently been shown that, contrary to the wide belief that a shift-enabled condition (necessary for any shift-invariant filter to be representable by a graph shift matrix) can be ignored because any non-shift-enabled matrix can be converted to a shift-enabled matrix, such a conversion in general may not hold for a directed graph with non-symmetric shift matrix. This paper extends this prior work, focusing on undirected graphs where the shift matrix is generally symmetric. We show that while, in this case, the shift matrix can be converted to satisfy the original shift-enabled condition, the converted matrix is not associated with the original graph, that is, it does not capture anymore the structure of the graph signal. We show via a counterexample, that a non-shift-enabled matrix cannot be converted to a shift-enabled one and still maintain the topological structure of the underlying graph, which is necessary to facilitate localized signal processing.

This study aimed to conduct a cross-cultural adaptation of the development of the cat-owner/dog-owner relationship scales. The method encompassed several stages: conceptual, item, semantic, operational, measurement, and functional equivalence. Processes included translations, synthesis of translations, back-translations, consensus on the English versions, external evaluation by the original authors, expert committee evaluation, and pre-tests. The study involved surveying 342 pet owners throughout Brazil using a 20-item questionnaire. Data analyses utilized confirmatory factor analysis, covariance-based modeling, and multigroup analysis. The techniques confirmed that the scale preserved its psychometric properties and showed no variance between dog and cat owners, indicating that the measured constructs are universal and unaffected by specific cultural nuances. Hence, the cross-cultural adaptation and validation of the scale facilitate applying and testing concepts and measures in diverse contexts, enriching our understanding of the dynamics between owners and their pets (dogs and cats) in different living situations. In addition, this research holds particular significance in Brazil, given the country’s vast cultural diversity.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

Fast-growing teak is widely cultivated in Indonesia to address the supply and demand of teak trees. However, efforts still need to be made to evaluate the condition of standing teak trees during their growth period. Studies on nondestructive testing (NDT) of wood based on electrical properties through dielectric spectroscopy (DS) are recently being developed, especially for standing tree evaluation. The study aimed to analyze the dielectric value of a fast-growing standing teak tree at frequency ranges 250 kHz – 60 MHz and to understand the relationships between physical and anatomical properties. Dielectric spectroscopy data were collected directly on the trees 4, 5, and 7 years old using a capacitance measurement system. Meanwhile, physical and anatomical samples were taken using a Ø 0.5 cm increment borer. The results showed that fiber length (FL), lumen diameter (LD), and fiber wall thickness (FWT) were significantly different at each tree age. This research found the optimal dielectric frequency to discriminate the wood properties in standing trees. There is a weak relationship (R= 0.2) in predicting the anatomical wood properties, while moderate to strong relationships (R= 0.4 to R= 0.8) are found in predicting wood density based on the selected frequency and moisture content variables. Further analyses and data processing can be improved by finding significant variables in the capacitance measurement system.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

The global environmental impact of plastic waste is significant, with only 9% being recycled, causing pollution and harming the environment and humans. Due to increased traffic, limited funding, and dwindling natural resources, Jordan's road network is deteriorating rapidly. Pavement performance can be improved through high-quality materials and sustainable construction practices. The research investigates using Polyethylene Terephthalate as a polymer additive in asphalt mixtures to enhance their properties. Basalt and limestone mixtures were applied to asphalt mixtures. The optimal binder content for the control mixture was 4.8% for basalt and 4.93% for limestone. When modified with 10% PET, the basalt mixture showed slightly better stability than the control mix, while higher PET proportions led to reduced strength. PET-modified mixtures consistently displayed higher flows and bulk densities, with a more pronounced impact on the basalt mixture. PET increased the air-void ratio in basalt but had minimal effect on VMA. PET offers economic and environmental advantages, saving 8.4% of the original bitumen cost. As a result, limestone mixture properties, which are inferior to basalt mixture properties, improved significantly compared to basalt mixture properties. PET has the potential to create sustainable and high-performing asphalt mixtures, providing valuable insights for road construction and environmental management.

The ZIPs (ZRT/IRT-like proteins) play critical roles in the absorption, transport, and intracellular balance of metal ions essential for various physiological processes in plants. However, little is known about the pan-genomic characteristics and properties of ZIP genes in cucumber (Cucumis sativus L.). In this study, we identified 10 CsZIP genes from the pan-genome of 13 C. sativus accessions. Among them, only CsZIP10 showed no variation in protein sequence length. We analyzed the gene structure, conserved domains, promoter cis-elements, and phylogenetic relationships of these 10 CsZIP genes derived from "9930". Based on phylogenetic analysis, the CsZIP genes were classified into three branches. Amino acid sequence comparison revealed the presence of conserved histidine residues in the ZIP proteins. Analysis of promoter cis-elements showed that most promoters contained elements responsive to plant hormones. Expression profiling in different tissues showed that most CsZIP genes were expressed at relatively low levels in C. sativus leave, stem, and tendril, and CsZIP7 and CsZIP10 were specifically expressed in root, indicating their potential involvement in the absorption and transport of metal ions. Transcriptomic data indicated that these 10 ZIP genes displayed responses to both downy mildew and powdery mildew, and CsZIP1 were significantly downregulated after both salt and heat treatments. In conclusion, this study deepens our understanding of the ZIP gene family and enhances our knowledge of the biological functions of CsZIP genes in C. sativus.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Severe malaria is a major public health concern in Angola, particularly among adults, with limited data on clinical outcomes and manifestations. The study therefore assessed the clinical manifestations and outcome of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango, Angola. The study retrospectively reviewed the individual records of patients over 14 years old, admitted for severe malaria during the first trimester of 2021 and 2022. World Health Organization (WHO) criteria were used to define severity. A total of 640 patients were recorded into the study, 167 in 2021 and 473 in 2022, distributed across the departments; Intensive Care Unit (ICU; n=81), Medicine (MED; n=458) and Infectiology (INF; n=101). The median age was 26 years and 59.4% were males. The most common manifestation of severe malaria was renal impairment (37.4%). The overall mortality rate was 7% and decreased considerably from 10.2% in 2021 to 5.9% in 2022. The increase in malaria cases during 2022 with increased in prevalence of life-threatening signs like renal impairment, jaundice and impaired conscience, underscores the urgent need for enhanced malaria control and surveillance strategies to mitigate morbidity and mortality, highlighting the potential for antimalarial drug resistance.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p&lt;0.001), with a shorter time between transplant and CMV (&lt;61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).

The strong competition in the automotive industry has required manufacturers to implement lean production, both with methods and techniques specific to Industry 4.0. At the same time, universities must provide graduates with specific skills for applying these new production methods and techniques. In this context, a Lean Learning Factory was developed in the Pitesti University Center, which allows students to learn, experiment, and research, in an environment similar to that of enterprises, the new Lean Manufacturing methods and techniques, and Industry 4.0. The research presented in this study had as its objective identifying the minimum number of repetitions necessary to train operators who serve two differently organized workstations, one classic, the other including digital techniques, but on which the same assembly operation is performed. Several indicators were considered in the analysis, such as the number of errors, the number of stops, the effective duration of the work cycle, and the percentage ratio between the standard duration of cyclical activities and the effective duration of the work cycle. The evolution of these indicators was mathematically modelled by regression functions, using the least squares method. The obtained results also highlight the usefulness of applying the DOJO method as a Lean manufacturing-specific learning technique and the efficiency of implementing digital techniques in work organization.

In this follow-up study, we aimed to assess the effectiveness of the “I do not smoke, I exercise”, anti-smoking preventive health education program. The program was based on the Theory of Planned Behavior supplemented with life-skills teaching and targeted at high school students. The intervention comprised ten one-hour online sessions, administered by physical education instructors. The study cohort comprised 222 students (109 boys, 113 girls) from 11 secondary schools, with an average age of 16.42 ± 1.36 years. Data collection involved pre- and post-intervention self-assessment questionnaires. The examined variables included attitudes towards smoking, intention to smoke, subjective norm, perceived behavioral control (PBC), knowledge about smoking, smoking behavior, exercise behavior, attitudes toward the program's implementation, and satisfaction with the program. Separate paired samples t-test revealed a significant improvement in students' knowledge about smoking, perceived behavioral control, and overall program satisfaction following the intervention. However, no significant changes were observed in the remaining variables. These findings suggest that the health education smoking prevention intervention incorporates techniques and strategies that influence the Perceived Behavioral Control variable, emphasizing students' strong interest in educationally theorized programs integrating technology into their design. Future studies should consider further examination of tobacco control strategies within the high school context.

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

Introduction: These days, obesity is considered an important factor for many medical problems such as diabetes mellitus, cardiovascular diseases and joint degeneration. Obesity is one of the leading causes of osteoarthritis and the need for arthroplasty. We aim to study the effect of obesity and the duration of knee replacement surgery.Method: A cross-sectional study was conducted at the orthopedic department between February 2023 and July 2023. We had 68 patients who underwent total knee replacement surgery. Variables like age, gender, smoking history, ASA grade, BMI, and side of injury (unilateral or bilateral) were studied.Results: Out of 68 patients, we had 37 (54.4 %) of patients were female. The most common age group was 44- 54 years. 60.3 % of patients were non-smokers. We had 50 patients with unilateral injury and the rest were bilateral. ASA grade II (51 patients) were more than ASA grade I (17 patients). In this study, 41 patients were obese and the duration for total knee replacement was 90 - 120 minutes, in contrast to overweight patients (75 – 90 minutes) and normal patients (60-75 minutes).Conclusion:We found a significant correlation between BMI and the duration of total knee replacement surgery. The time could be doubled if the arthroplasty was bilateral.

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

Nowadays the dynamism induced by the constant change of strategic decisions on the markets produces an extra difficulty in the management of an organization. The strategic decisions made by managers can become obsolete in a short period of time. One of the major difficulties in managing a commercial organization is to predict, with some precision degree, the impact some strategic decisions have on the financial results. Business Intelligence (BI) is an area widely used to help managers to make strategic decisions. But the methods used, behind the scenes, to achieve the conclusions are kept secret by BI company-based services. Modelling the environment can be a good option to study the impact of an action, provided by a strategic decision, in a real environment. A good model should give an approximate result of an action applied to a previous state of the environment. Artificial Neural Networks (ANNs) are proven to be excellent in modeling environments with some level of data noise. The same strategic action can have different results in different organizations. A tool that allows an evaluation of a strategic action applied to an environment should have a major importance in the management scope. Modeling the environment should save time and money for the organization to improve the performance of the strategic plan. If one evaluates the state of the environment after a strategic action being applied, it can be possible to mitigate the risk of failure of the strategic plan. As we will be able to verify, it is possible to use ANNs to model strategic environments that should allow the prediction of sales and operating results by the used strategies with some precision, although the level of success will be directly related with the user’s necessity.

Polypharmacy and malnutrition are common health issues among older adults. In older people, there is a high prevalence of polypharmacy and malnutrition, and preliminary data also indicates that there is a significant of Food Supplements (FS) use, increasing the risk of duplication of thera-pies and several adverse reactions and drug-FS and FS-FS interactions. The intervention of health professionals in mitigating these risks is essential. This review not only underscores and discusses the potential association between polypharmacy, malnutrition, and food supplements but also presents current scientific evidence on polypharmacy, malnutrition, and the use of food supplements by the elderly. The work reviews the challenges, advantages and risks of using FS for the elderly who are polymedicated and/or malnourished, focusing on the good practices needed to support healthy ageing. In this regard, the paper intends to help health professionals better deal with the issue of polypharmacy and the use of multiple FS to overcome the malnutrition problem and improve the health and well-being of older adults.

There is a growing trend among consumers to seek out natural foods and products with natural ingredients. This shift in consumer preferences had a direct impact on both food and pharmaceutical industries, leading to a focus of scientific research and commercial efforts to meet these new demands. The aim of this work is to review recent available scientific data on foods of interest, such as artichoke, gooseberry, and polygonoideae plants, as well as olive oil and red raspberries. Interestingly, the urgency of solutions to the climate change emergency has brought new attention to by-products of grapevine bunch stem and cane, which have been found to contain bioactive compounds with potential health benefits. There is a pressing need for a faster process of translating scientific knowledge from the laboratory to real-world applications, especially in the face of the increasing societal burden associated to non-communicable diseases (NCDs), environmental crises, the post-pandemic world, and ongoing violent conflicts around the world.

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 95.45% of our samples. Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction (PCR), immunohistochemistry (IHC) and tissue microarray (TMA) analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffused Id-1 overexpression, which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Laser direct writing allows for the fabrication of complex structures, which is particularly advantageous in micro-optic applications. However, the increasing demand for optics quality requires the lowest optical power loss, which can occur from unwanted reflections. This research demonstrates the possibility of forming an anti-reflective coating on hybrid-polymer micro-lenses fabricated by employing laser direct writing (LDW), without changing their geometry. Such coating deposited by atomic layer deposition (ALD) decreased the reflection from 3.3 % to 0.1 % at the wavelength of 633 nm for one surface of SZ2080™.

The subject of study in the article is the method of industrial equipment vibration diagnostics using Allan variance. The goal is to increase the precision and accuracy of industrial equipment's vibration diagnostics processes by developing and implementing IoT-oriented solutions based on intelligent sensors and actuators per the IEEE 1451.0-2007 standard. Tasks: justify the feasibility of using platform-oriented technologies for vibration diagnostics of industrial equipment and choose a cloud service for the implementation of the platform; develop software and hardware solutions of the IoT platform for vibration diagnostics of industrial equipment; calibrate the vibration diagnostics system and check the measurement precision and accuracy. The methods used are the microservice approach, multilevel architecture, and assessing equipment state-based Allan variance. We obtained the following results. The architecture of the IoT system for vibration diagnostics of industrial equipment developed and presented in the article is three-level. The level of autonomous sensors provides readings of vibration acceleration indicators and transmits data to the Hub level, which is implemented based on a BeagleBone single-board microcomputer through the BLE digital wireless data transmission channel. BeagleBone computing power provides work with artificial intelligence algorithms. At the third level of the server platform, the tasks of diagnosing and predicting the condition of the equipment are solved, for which the Dictionary Learning algorithm implemented in the Python programming language is applied. Verifying the accelerometer calibration method for vibration diagnostics of industrial equipment was performed using a unique stand. Correct operation of the entire system is confirmed by the coincidence of expected and measured results. In the next step, we plan the development of additional microservices that will provide the possibility of using time series analysis methods and modern artificial intelligence technologies for complex diagnostics and forecasting of the equipment state.

In aerobic environments, bacteria are exposed to reactive oxygen species (ROS). To avoid an excess of ROS, microorganisms are equipped with powerful enzymatic and non-enzymatic antioxidants. Corynebacterium glutamicum, a widely used industrial platform organism, uses mycothiol (MSH) as major low molecular weight (LMW) thiol and non-enzymatic antioxidant. In aerobic bioreactor cultivations C. glutamicum becomes exposed to oxygen concentrations surpassing the air saturation, which are supposed to constitute a challenge for the intracellular MSH redox balance. In this study, the role of MSH was investigated at different oxygen levels (pO2) in bioreactor cultivations in C. glutamicum. Despite the presence of other highly efficient antioxidant systems, such as catalase, the MSH deficient ΔmshC mutant was impaired in growth in bioreactor experiments performed at pO2 values of 30%. At a pO2 level of 20% this growth defect was abolished, indicating a high susceptibility of the MSH-deficient mutant towards elevated oxygen concentrations. Bioreactor experiments with C. glutamicum expressing the Mrx1-roGFP2 redox biosensor revealed a strong oxidative shift in the MSH redox potential (EMSH) at pO2 values above 20%. This indicates, that the LMW thiol MSH is an essential antioxidant to maintain the robustness and industrial performance of C. glutamicum during aerobic fermentation processes.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

In the context of sustainable development, integrating the work aspect into health promotion systems is essential, ensuring that employees maintain a healthy balance between their professional and personal lives, which respects and amplifies the potential of every individual. Lately, there has been a noticeable shift of medical professionals from the public to the private sector. This trend paints a bleak picture, highlighting the vulnerabilities of a system teetering on the brink of failure, with significant impacts on patient care. Among the myriad reasons behind this shift, burnout stands out prominently. Medical professionals face increasing pressures due to understaffing, limited organizational support, and insufficient resources, leading to feelings of cynicism, exhaustion, and detachment from their roles. Utilizing the Maslach et al. questionnaire, we assessed the risk of burnout among physicians in public hospitals to identify and underscore preventive measures and improvements, correlating our findings with key aspects of organizational empowerment. Our research indicates that enhancing interpersonal relationships and resources—both within teams and between the organization and its physicians—is crucial for the revival of the healthcare system. This approach aims at improving the delivery of healthcare services and offering appropriate recognition to healthcare professionals, aligning with the principles of sustainable employment.

In this review, we summarize recent progress in crystal growth and understanding the influence of crystal structure on the superconductivity in pure and Pb-doped Bi2Sr2CuOy (Bi-2201) materials belonging to the overdoped region of high temperature cuprate superconductors. The crystal growth of Bi-2201 superconductors faces challenges due to intricate materials chemistry and lack of knowledge of corresponding phase diagrams. Historically, a crucible-free floating zone method has emerged as the most promising growth approach for these materials, resulting in high-quality single crystals. This review outlines the described in the literature and the authors' synthesis endeavors, encompassing Pb-doped Bi-2201 crystals, detailed structural characterization of as-grown and post-growth annealed samples, and highlights optimal growth conditions that yield large-size, single-phase, and compositionally homogeneous Bi-2201 single crystals.

The study findings revealed significant variability in various wood properties among different genetic families, although the static modulus of elasticity did not exhibit significant differences between the chosen genetic families. All measured wood properties decreased from the bottom to the top of the model trees. Wood hardness displayed a moderately negative correlation with wood density and weak correlations with MOE and MOR. Given the weak correlations between wood hardness and other wood mechanical properties, it is suggested that the MOEdyn would be a more suitable trait for genetic studies.

Craters are the most prominent geomorphological features on the surface of celestial bodies, which is playing a crucial role in studying the formation and evolution of celestial bodies, as well as in landing and planning for surface exploration. Currently, the main automatic crater detection models and datasets focus on the detection of large and medium craters. In this paper, we created 23 small lunar crater datasets for model training based on the Chang’E-2 (CE-2) DOM, DEM, Slope, and integrated data with 7 kinds of visualization stretching methods. And then, we proposed the YOLO-Crater model for Lunar and Martian small crater detection by replacing EioU and VariFocal loss to solve the crater samples imbalance problem and introducing a CBAM attention mechanism to mitigate interference from the complex extraterrestrial environment. The results show that the accuracy (P = 87.86%, R = 66.04%, and F1 = 75.41%) of the Lunar YOLO-Crater model based on the DOM-MMS (Maximum-Minimum Stretching) dataset is the highest and better than that of YOLOX model. And the Martian YOLO-Crater, trained by the Martian dataset from the 2022 GeoAI Martian Challenge, achieves good performance with P = 88.37%, R = 69.25%, and F1 = 77.65%. It indicates that the YOLO-Crater model has a strong transferability and generalization capability, which can be applied to detect small craters on the Moon and other celestial bodies.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Fabrication of a true-3D inorganic ceramic with resolution down to nanoscale using sol-gel resist precursor is demonstrated. The method has an unrestricted free-form capability, control of the fill-factor, and high fabrication throughput. A systematic study of the proposed approach based on ultrafast laser 3D lithography of organic-inorganic hybrid sol-gel resin followed by a heat treatment enabled formation of inorganic amorphous and crystalline composites guided by the composition of the initial resin. The achieved resolution of 100 nm was obtained for 3D patterns of complex free-form architectures. Fabrication throughput of 50×10³ voxels/s is achieved; voxel - a single volume element was recorded by a single pulse exposure. After a subsequent thermal treatment, ceramic phase was formed depending on the temperature and duration of the heat treatment as validated by Raman micro-spectroscopy. The X-ray diffraction (XRD) revealed a gradual emergence of the crystalline phases at higher temperatures with a signature of cristobalite SiO₂, a high-temperature polymorph. Also, the tetragonal ZrO₂ phase known for its high fracture strength was observed. This 3D nano-sintering technique is scalable from nano- to millimeter dimensions and opens a conceptually novel route for optical 3D nano-printing of various crystalline inorganic materials defined by an initial composition for diverse applications for microdevices in harsh physical and chemical environments and high temperatures.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on the smart cane. The intelligent guide system relies on 2D LiDAR, RGB-D camera, IMU, GPS, Jetson nano B01, STM32 and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on Cartographer algorithm, thus achieving Simultaneous localization and mapping (SLAM). At the same time, through the improved yolov5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved yolov5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the wheels and omnidirectional wheels at the bottom of the smart cane, and give the smart cane a self-leading blind guide function like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach the predetermined destination, and can quickly and effectively identify the obstacles on the way out. The laser SLAM speed of this system is 25~31FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor envionments. The improved yolov5 helps to identify 86 types of objects, the recognition rate for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26FPS.

Introduction: Bone fractures may be the result of high force impact or stress, or a minimal trauma injury as a result of certain medical conditions that weaken the bones, such as osteoporosis, osteopenia, bone cancer, or osteogenesis imperfecta, where the fracture is then properly termed a pathologic fracture. Bone cancer can be primarily or secondary to metastasis. Case presentation: We report a rare case of left humerus fracture in a 59-year-old male patient due to metastatic renal cell carcinoma. Our patient had no important past medical history. He suffered from two months of left arm pain, moderate disability and fever at night. Analgesics consumption resulted in minimal relieve. Trauma history was negative. X-ray of the left arm showed an osteolytic lesion with humerus fracture. Abdominal computed tomography with contrast showed right renal mass.Radical right nephrectomy was performed in addition to alignment nailing of the left humerus fracture with biopsy. Pathology report documented clear cell carcinoma with metastatic bone. The treatment was completed by chemotherapyDiscussion: Secondary bone tumors are metastatic lesions which have spread from other organs, most commonly carcinomas of the breast, lung, and prostate, and rarely from kidney. In some cases, bone metastasis could be the first symptoms of renal cell carcinoma. Conclusion: suspected pathological bone fractures should be investigated completely. It may hide a tumor as a cause.

Neuropsin is a brain-expressed extracellular matrix serine protease that governs synaptic plasticity through activity-induced proteolytic cleavage of synaptic proteins. Its substrates comprise several molecules central to structural synaptic plasticity, and studies in rodents have documented its role in cognition and the behavioral and neurobiological response to stress. Intriguingly, differential usage of KLK8 (neuropsin gene) splice forms in the fetal and adult brain has only been reported in humans, suggesting that neuropsin may serve a specialized role in human neurodevelopment. Through systematic interrogation of large-scale genetic data, we review KLK8 regulation in the context of mental health and provide a summary of clinical and preclinical evidence supporting a role for neuropsin in the pathogenesis of mental illness.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Background: Patients with allergic rhinitis (AR) have bothersome symptoms that may assess using the visual analog scale (VAS). Asthma frequently is associated with AR. The present study investigated the role of VAS in children with newly-diagnosed AR. Methods: Parameters were VAS for nasal and asthma symptoms, and doctor’s perception of these diseases, medication use, and asthma comorbidity. Results: 67% of AR children had asthma. Severity of perceived nasal symptoms was associated with more intense asthma symptoms and doctor’s perception of disease severity (p<0.001 and p=0.02, re-spectively. Conclusions: Allergic rhinitis frequently is associated with asthma in child-hood. Symptom perception assessment using VAS is a simple tool for assessing their intensity. Moreover, the severity of nasal symptoms is associated with asthma symptom severity. Therefore, asthma should be carefully considered in AR children and require appropriate symptom perception assessment.

L-asparaginase from bacterial sources have been used in antineoplastic treatments and the food industry. A novel type II L-a sparaginase encoded by the N-truncated gene ansZP21 of halotolerant Bacillus subtilis CH11 isolated from Chilca salterns in Peru was expressed using a heterologous system in Escherichia coli BL21 (DE3)pLysS. The recombinant protein was purified using one-step nickel affinity chromatography and exhibited activity of 234.38 U mg-1 and a maximum catalytic activity at pH 9.0 and 60 °C. The enzyme shows a homotetrameric form with an estimated molecular weight of 155 kDa by gel filtration chromatography. The enzyme half-life at 60 °C was 3 h 48 min, and L-asparaginase retained 50% of initial activity for 24 h at 37 °C. The activity was considerably enhanced by KCl, CaCl2, MgCl2, mercaptoethanol, and DL-dithiothreitol (p-value &lt; 0.01). Moreover, the Vmax and Km were 145.2 µmol mL-1 min-1 and 4.752 mM, respectively. These findings evidence a promising novel type II L-asparaginase for future industrial applications.

A pandemic happens when a novel influenza A virus is able to infect and transmit efficiently to a new, distinct host species. Although the exact timing of pandemics is uncertain, it is known that both viral and host factors play a role in their emergence. Species-specific interactions between the virus and the host cell determine the virus tropism. These include binding and entering cells, replicating the viral RNA genome within the host cell nucleus, assembling, maturing, and releasing the virus to neighbouring cells, tissues, or organs before transmitting it between individuals. Influenza has a vast and antigenically varied reservoir. In wild aquatic birds, the infection is typically asymptomatic. Avian influenza virus (AIV) can cross into new species, and occasionally, it can acquire the ability to transmit from human to human. A pandemic might occur if a new influenza virus acquires enough adaptive mutations to maintain transmission between people. This review highlights the key determinants AIV must achieve to initiate a human pandemic and describes how AIV mutates to establish tropism and stable human adaptation. Understanding the tropism of AIV may be crucial in preventing virus transmission in humans and may help design vaccines, antivirals and therapeutic agents against the virus.