Recently, selection in pigs has been focused on improving the lean meat content in carcasses; this focus has been most evident in breeds constituting a paternal component in breeding. Such sire-breeds are used to improve the meat quantity of cross-breed pig lines. However, even in one breed, a significant variation in the meatiness level can be observed. In the present study, the comprehensive analysis of genes and microRNA expression profiles in porcine muscle tissue was applied to identify the genetic background of meat content. The comparison was performed between whole gene expression and miRNA profiles of muscle tissue collected from two sire-line pig breeds (Piertain, Hampshire). The RNA-seq approach allowed the identification of 627 and 416 differentially expressed genes (DEGs) between pig groups differing in terms of loin weight between Pietrain and Hampshire breeds, respectively. The comparison of miRNA profiles showed differential expression of 57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18 miRNAs were selected as differentially expressed in both breeds and potentially related to muscle development. According to Gene Ontology analysis, identified DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid biosynthesis and regulation of the actin cytoskeleton. The most deregulated pathways dependent on muscle mass were the Hippo signalling pathway connected with the TGF-beta signalling pathway and controlling organ size via the regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis. The identified target genes were also involved in pathways such as the FoxO signalling pathway, signalling pathways regulating pluripotency of stem cells and the PI3K-Akt signalling pathway. The obtained results indicate molecular mechanisms controlling porcine muscle growth and development. Identified genes (SOX2, SIRT1, KLF4, PAX6 and genes belonging to the transforming growth factor beta superfamily) could be considered candidate genes for determining muscle mass in pigs.

We investigate the human sustainability of ICT and management changes using a French linked employer-employee survey on organizational changes and computerization (COI). We approach the human sustainability of changes through the evolutions of work intensity, skill utilization and the subjective relationship to work. We compare in the private sector and the State civil service the impacts of ICT and management changes on the evolution of these three dimensions of work experience. We find that when ICT and management changes are intense, they are positively associated in the public sector with work intensification and new knowledge. In the private sector ICT and management changes increase the use of skills, but at a rate decreasing with their intensity and without favoring the accumulation of new knowledge. However, their impacts on the subjective relationship to work are much stronger, with public sector employees expressing discouragement as well as the feeling of an increased effort-reward imbalance when private sector employees become more committed. We tested that the self-selection of employees, the specific sources and paths of changes and the implementation of performance pay did not explain this divergence. We identify two partial explanations: one is related with employee turnover in the private sector, the other one with the role of trade unions. These results suggest that the human sustainability of ICT and management changes depends on their intensity and on how their implementation takes into account the institutional context of the organization.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

Elevated antimony concentrations in aqueous environments from anthropogenic sources is becoming of global concern, here iron oxides are known to strongly adsorb aqueous antimony species with different oxidation states, but the effect of silica on the removal characteristics is not well understood despite being a common component in the environment. In this study, ferrihydrite was synthesized at various Si/Fe molar ratios to investigate its adsorption and co-precipitation behaviors with aqueous antimony anionic species, Sb(III) and Sb(V). The XRD analyses of the precipitates showed two broad diffraction features at approximately 35° and 62° 2θ, which are characteristic of 2-line ferrihydrite, no significant shifts in peak positions in the ferrihydrite regardless of the Si/Fe ratios. The infrared spectra showed a sharp band at ~990 cm⁻¹, corresponding to asymmetric stretching vibrations of Si-O-Fe bonds which increased in intensity with increasing Si/Fe molar ratios. Further, the surface charge on the precipitates became more negative with increasing Si/Fe molar ratios. The adsorption experiments indicated that Sb(V) was preferentially adsorbed at acidic conditions and decreased dramatically with increasing pH while the adsorption rate of Sb(III) ions was independent of pH, however, the presence of silica suppressed the adsorption of both Sb(III) and Sb(V) ions. The results showed that Sb(III) and Sb(V) ions were significantly inhibited by co-precipitation with ferrihydrite even in the presence of silica by isomorphous substitution in the ferrihydrite crystal structure.

Meta-aminobenzoic acid, an important model system in the study of polymorphism and crystallization of active pharmaceutical ingredients, exist in water in both the nonionic (mABA) and zwitterionic (mABA^±) forms. However, the constituent molecules of the polymorph that crystallizes from aqueous solutions are zwitterionic. This study reports atomistic simulations of the events surrounding the early stage of crystal nucleation of meta-aminobenzoic acid from aqueous solutions. Ab initio molecular dynamics was used to simulate the hydration of mABA± and mABA, and to quantify the interaction of these molecules with the surrounding water molecules. Density functional theory calculations were conducted to determine the low-lying energy conformers of meta-aminobenzoic acid dimers and compute the Gibbs free energies in water of nonionic, (mABA)₂, zwitterionic, (mABA^±)₂ and nonionic-zwitterionic, (mABA)(mABA^±), species. Classical molecular dynamics simulations of mixed mABA–mABA^± aqueous solutions were carried out to examine the aggregation of meta-aminobenzoic acid. According to these simulations the selective crystallization of the polymorph which constituent molecules are zwitterionic is driven by the formation of zwitterionic dimers in solution, which are thermodynamically more stable than (mABA)₂ and (mABA)(mABA^±) pairs. This work represents a paradigm of the role of molecular processes during the early stages of crystal nucleation in affecting polymorph selection during crystallization from solution.

In the second half of the 19th century a wave of modernisation, industrialisation and urbanisation swept the Nordic countries, catapulting what had until then been lagging and primarily rural countries into modernity. These major upheavals, however, also plunged the Nordic countries into a profound social and cultural crisis resulting from their consciousness of their own backwardness vis-a-vis the countries on the European continent, as well as the recognition that a nostalgic nationalism recalling a mythical past had become obsolete in the industrial age. In response to this crisis, a life reform movement emerged that was based on Arts and Crafts movements as well as various artistic and literary reform movements and—equally absorbing rural traditions and progressive social ideas—tried to establish a new national everyday culture. In this article, the two key terms coined by Ellen Key, “Festive Customs” (‘festvanor’) and “Everyday Beauty” (‘vardagsskönhet’)—the programmatic core of the Nordic life reform movement—are analysed and illustrated in various typical manifestations. It also examines to what extent the Nordic life reform movement with these two key concepts as its core agenda found expression in arts and crafts, in painting as well as in the architecture of the late nineteenth and early twentieth century and contributed to the progress of social and cultural renewal.

Baobab (Adansonia digitata) leaves are usually used in dry form in the preparation of a soup known as ‘miyan kuka’ in Northern Nigeria. The leaves are believed to have nutritional and medicinal benefits and have been used for those purposes in Africa and Asia. However there has been limited research on the detailed constituents of the dry leaves. In this study, phytochemical, elemental and proximate analyses of stored, sun and shade-dried baobab leaves were conducted. The results revealed a great variation in the nutritional contents of the leaves. The study reveals that the leaves are rich in phytochemicals such as glycosides, saponins, steroids and flavonoids while alkaloids, tannins and resins are absent. Also, they are important source of minerals such as zinc, copper, iron and manganese. In addition, they are rich in fibre, crude protein, nitrogen and ash. Contrasting responses were obtained in the samples studied. The implications of these responses are discussed in relation to crop yield.

It is well known that that there is an intrinsic link between the financial and energy sectors, which can be analyzed through their spillover effects, which are measures of how the shocks to returns in different assets affect each other’s subsequent volatility in both spot and futures markets. Financial derivatives, which are not only highly representative of the underlying indices, but can also be traded on both the spot and futures markets, include Exchange Traded Funds (ETFs), a tradable spot index whose aim is to replicate the return of an underlying benchmark index. When ETF futures are not available to examine spillover effects, “generated regressors” are useful for constructing both Financial ETF futures and Energy ETF futures. The purpose of the paper is to investigate the co-volatility spillovers within and across the US energy and financial sectors in both spot and futures markets, by using “generated regressors” and a multivariate conditional volatility model, namely Diagonal BEKK. The daily data used are from 1998/12/23 to 2016/4/22. The data set is analyzed in its entirety, and are also subdivided into three distinct subsets. The empirical results show there is a significant relationship between the Financial ETF and Energy ETF in the spot and futures markets. Therefore, financial and energy ETFs are suitable for constructing a financial portfolio from an optimal risk management perspective, and also for dynamic hedging purposes.

Glycerol is a subproduct of biodiesel production and represents an important problem when generated in large scale. Alternatives that can utilize this unrefined byproduct is of potential interest. It is herein described the synthesis of a series of 1,2,3-triazoles using glycerol as starting material. The key step involved in the preparation of triazolic derivatives corresponded to the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicide activity was assessed in vitro against Colletotrichum gloeosporioides, the causing agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)cyclohexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency on controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to control C. gloeosporioides.

In this study, we investigated the effects of Akebia quinata ethanol extract (AE), Akebia quinata sikhye (AS), and Akebia quinata water extract (AW) on alcohol-induced liver injury in rats. The hepatoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects of AE, AS, and AW were examined. Experimental animals were randomly divided into five groups: normal, ethanol, AE (10 mL/kg), AS (10 mL/kg), and AW (10 mL/kg). Each group was administered the respective treatment orally once per day for 21 days. CYP2E1 mRNA expression was significantly lower in the AE, AS, and AW groups than that in the ethanol group. Pro-inflammatory cytokines including cyclooxygenase-2, IL-6, and TNF-α increased significantly in the ethanol group but these increases were ameliorated with AE, AS, and AW treatment. Moreover, the expression of the apoptosis-associated proteins Bax, p53, procaspase-3, and PARP decreased after treatment with AE, AS, and AW. The expression of antioxidant enzymes including BCL-2, SOD, and GST slightly decreased in the ethanol group, but AE, AS, and AW treatment augmented their activities. AQ extracts and AS attenuated ethanol-induced increases in the levels of phosphorylated p-AKT, p-ERK, and p-JNK. These results demonstrate that AQ is a competence indicator for inhibiting alcoholic liver injury.

Saliency detection in synthetic aperture radar (SAR) image is a difficult problem. This paper proposed a multitask saliency detection (MSD) model for the saliency detection task of SAR image. Firstly, we extract four features of SAR image as the input of the MSD model, which include the intensity, orientation, uniqueness and global contrast. Then, the saliency map is generated by the multitask sparsity pursuit (MTSP) which integrates the multiple features collaboratively. Subjective and objective evaluation of the MSD model verifies its effectiveness. Based on the saliency maps of the source images, an image fusion method is proposed for the SAR and color optical image fusion. The experimental results of real data show the proposed image fusion method is superior to the presenting methods in terms of several universal quality evaluation indexes, as well as in the visual quality. The salient areas in the SAR image can be highlighted and the spatial and spectral details of color optical image can also be preserved in the fusion result.

For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study we aimed to investigate whether abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with COVID-19-induced ARDS. Plasma ET-1 levels were measured in 18 mechanically ventilated COVID-19-induced ARDS patients, with simultaneous central venous and systemic arterial blood sampling on Days 1 and 3 following ICU admission. Two age- and sex-matched non-COVID-19 control groups were also used [mechanically ventilated non-COVID-19 critically ill and ARDS patients]. On ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and venous ET-1 levels compared to non-COVID-19 ARDS and critically ill patients (p< 0.05). The arterial:venous (A:V) ET-1 ratio was higher in the non-COVID-19 ARDS patients [1.06 (0.93-1.20)] compared to the other two groups (p< 0.05). The A:V ratio was 0.63 (0.49-1.02) in the COVID-19-induced ARDS patients and 0.79 (0.52-1.11) in the non-COVID-19 critically ill patients. On Day 3, the A:V ratio in all three groups was < 1. The COVID-19 patient group was then divided based on 28-day ICU mortality. Although arterial and venous levels did not differ, the A:V ratio was statistically significantly higher on ICU admission in the non-survivors [0.95 (0.78-1.34)] vs 0.57 (0.48-0.92), p= 0.027]. Measurement of ET-1 clearance via A:V plasma ET-1 levels on ICU admission may assist in predicting outcomes in COVID-19 critically ill patients.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might have reduced the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patient with diabetes and those with obesity, as well as considering sex-based differences. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to develop a personalized approach.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

Various wood fibres, including pine and flax, are used in wood–plastic composites (WPCs). This paper studies the effect of the lignin content on the morphological and thermal degradation and damage due to the ultraviolet (UV) aging of polypropylene/flax (PP-flax) and polypropylene/pine (PP-pine) fibres composites. Flax and pine fibres exhibited distinct densities of 1.51 and 1.47 g/cm³, respectively, potentially influenced by growth factors and varying compositions of light substances, such as hemicellulose, lignin, and impurities. The thermal decomposition mass loss increased proportionally with the percentage of lignin in the fibre. From 238°C to 390°C, the pine fibre exhibited a 72% mass loss compared to flax fibre, which showed a 54% mass loss, owing to the higher lignin content in pine fibres. Based on differential scanning calorimetry (DSC), the fibre composition affected the material melting temperature. Moreover, DSC curves revealed a higher degree of crystallinity in the case of the PP-flax biocomposite (12%) compared to pure polypropylene (9%) and PP-pine (6%). This result can be attributed to the high content of crystalline components in flax fibres, such as cellulose. Acoustic emissions analysis confirmed that the high lignin content delays degradation and mitigates the appearance of microcracks on the surface of the PP-pine biocomposite. Overall, the study provides valuable data for understanding the UV degradation phenomenon in biocomposites and highlights the influence of fibre composition on material performance.

Cross-institutional secondary use of medical data benefits from structured semantic annotation, which, ideally, enables matching and merging semantically related data items from different sources and sites. While numerous medical terminologies and ontologies, as well as some tooling, exist to support such annotation, cross-institutional data usage based on independently annotated datasets is challenging for multiple reasons: the annotation process is resource intensive and requires a combination of medical and technical expertise since it often requires judgment calls to resolve ambiguities resulting from non-uniqueness of potential mappings to various levels of ontological hierarchies and relational and representational systems. Divergent resolution of such ambiguities can inhibit joint cross-institutional data usage based on semantic annotation since data items with related content from different sites will not be identifiable based on their respective annotations if different choices were made without further steps such as ontological inference, which is still an active area of research. We hypothesize that a collaborative approach to semantic annotation of medical data can contribute to more resource efficient and high-quality annotation by utilizing prior annotational choices of others to inform the annotation process, thus both speeding up the annotation itself and fostering a consensus approach to resolving annotational ambiguities by enabling annotators to discover and follow pre-existing annotational choices. Therefore, we have implemented a prototypical Collaborative Annotation Tool (CoAT), evaluated its usability, and present first inter-institutional experiences with this novel approach to promoting practically relevant interoperability driven by use of standardized ontologies.

Rice production in the Anhui province is threatened by fungal diseases. We obtained twenty-five fungal isolates from rice and wild-rice leaves showing leaf spot disease collected along the Yangtze River. A phylogenetic analysis based on internal transcribed spacer (ITS), translation elongation factor 1 alpha (TEF1-α), and beta tubulin (TUB2) sequences revealed that one isolate (SS-2-JB-1B) grouped with Nigrospora shaerica, one (QY) with Nigrospora chinensis, twenty-two with Ngrospora oryzae, and one strain (QY-2) grouped in its own clade, related to but clearly different from N. oryzae. Nineteen tested isolates including sixteen strains from the N. oryzae clade and the three isolates of the other three clades, caused disease on detached rice leaves. The three isolates that did not belong to N. oryzae were also able to cause disease on rice seedlings, suggesting that they were rice pathogens. Isolate QY-2 differed from the other isolates in terms of colony mor-phology, cell-size, and susceptibility to fungicides, indicating that this isolate represents a new species that we named Nigrospora anhuiensis. Our analysis showed that N. sphaerica, N. chinensis, and the new species N. anhuiensis can cause rice leaf spot disease in the field. This research pro-vides new knowledge for understanding rice leaf spot disease.

This manuscript explores sustainable agriculture's role in mitigating environmental challenges and meeting the nutritional needs of a growing global population. The objective is to assess the impact of different fertilizers on two distinct tomato-growing soils, each characterized by unique chemical and biological properties. The study compares four fertilizer treatments: Additionally, it evaluates the environmental implications of these fertilizers, focusing on their Carbon and Water Footprints. The findings indicate significant improvements in soil quality with SBO fertilizer. Both soils experienced a shift towards a near-neutral pH, increased organic matter content, and heightened microbial biomass. Enzyme activities were notably superior in SBO-treated soils. Life Cycle Assessment (LCA) results demonstrate that the SBO-based system is the most sustainable, with the lowest Carbon footprint. NPK exerts the highest environmental impact. The Water Footprint analysis aligns with these results, showing that SBO requires the least water for tomato production. In summary, this study underscores the significance of sustainable fertilization practices in improving soil quality and reducing environmental footprints in agriculture, offering potential benefits for food production and environmental conservation.

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn's disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.. In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA). We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels. In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels. Aims its connections with We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression. In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels. This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

Carbon (C) cycle n inland waters, including its concentrations and carbon dioxide (CO2) emis-sions from water surfaces are at the forefront of biogeochemical studies, especially in the re-gions, strongly impacted by on-going climate change. Towards better understanding of C stor-age, transport and emission in Central Asian mountain regions, extremely poorly studied until now, here we carried out systematic measurements of dissolved C and CO2 emissions in 15 riv-ers and 5 lakes located along a macro-transect of various natural landscapes in the Sayan-Altai mountain region, from high mountains of the Western Sayan in the northwest of Tyva to arid (dry) steppe and semi-deserts in intermountain basins of the southeast of Tyva, the border with Mongolia. New data on major hydrochemical parameters, CO2 fluxes by floating chambers, dis-solved organic and inorganic carbon concentrations collected over four main hydrological sea-sons allowed to assess the current C biogeochemical status of these water bodies in order to judge possible future changes under climate warming. We further tested the impact of perma-frost, river watershed size, lake area and climate parameters as well as ‘internal’ biogeochemical drivers (pH, mineralization, organic matter quality and bacterial population) on CO2 concentra-tion and emissions in lakes and rivers of this region, and compared them with available data on other subarctic and mountain settings.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. In two of them, the optimized geometry was determined in the monomer, cyclic dimer and staking forms using the B3LYP, M06-2X and MP2 methods. The effect of the para-substitution in the aryl ring was evaluated based on the changes in the molecular structure and atomic charge distribution of the triazole ring. Several relationships were obtained that could facilitate the selection of the substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to the functional calculations on the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE).

To evaluate the relative importance of IGF-I expression in various cell types for endochon-dral ossification, we quantified the trabecular bone at the secondary spongiosa and epiphysis of the distal femur in 8-12-week-old male mice with a global knockout of the Igf-I gene as well as conditional deletion of the Igf-I gene in osteoblasts, chondrocytes, osteo-blasts/chondrocytes, and their corresponding control wild type littermates. The osteoblast-, chondrocyte- and osteoblast/chondrocyte-specific Igf-I conditional knockout mice were generated by crossing Igf-I floxed mice with Cre transgenic mice in which Cre expression is under the control of Col1α2 or Col2α1 promoter. We found that global disruption of Igf-I resulted in 80% and 70% reduction in bone size, which is defined as total volume, at the secondary spongiosa and epiphysis of the distal femur, respectively. Abrogation of Igf-I in Col1α2-producing osteoblasts, but not Col2α1-producing chondrocytes, decreased bone size by 25% at both the secondary spongiosa and epiphysis while deletion of the Igf-I globally or specifically in osteoblasts or chondrocytes reduced trabecular bone mass by 25%. By contrast, global Igf-I knockout but not conditional knockout of Igf-I in osteoblasts and/or chondrocytes reduced trabecular bone mass in the epiphysis. The reduced trabecu-lar bone mass at the secondary spongiosa in osteoblast- and/or chondrocyte-specific Igf-I conditional knockout mice is caused by reduced trabecular number and increased trabec-ular separation. Immunohistochemistry studies revealed that expression levels of chon-drocyte (COL10, MMP13) and osteoblast (BSP) markers were reduced in the secondary spongiosa and the epiphyses in the global Igf-I knockout mice. Our data indicate that local and endocrine IGF-I actions in bone are pleiotropic and dependent on cell type as well as the bone compartment where IGF-I acts.

In this study, our primary objective was to analyze the tradeoff between accuracy and complexity in machine learning models, with a specific focus on the impact of reducing complexity and entropy on the production of landslide susceptibility maps. We aimed to investigate how simplifying the model and reducing entropy can affect the capture of complex patterns in the susceptibility maps. To achieve this, we conducted a comprehensive evaluation of various machine-learning algorithms for classification tasks. We compared the performance of these algorithms in terms of accuracy and complexity, considering both "before" and "after" scenarios of dimensionality reduction using Principal Component Analysis (PCA). Our findings revealed that reducing complexity and lowering entropy can lead to an increase in model accuracy. However, we also observed that this reduction in complexity comes at the cost of losing important complex patterns in the produced landslide susceptibility maps. By simplifying the model and reducing entropy, certain intricate relationships and uncertain patterns may be overlooked, resulting in a loss of information and potentially compromising the accuracy of the susceptibility maps. The analysis encompassed a diverse range of machine learning algorithms, including Random Forest (RF), Extra Trees (EXT), XGboost, LightGBM, Catboost, Naive Bayes (NB), K-Nearest Neighbors (KNN), Gradient Boosting Machine (GBM), and Decision Trees (DT). Each algorithm was evaluated for its strengths and limitations, considering the tradeoff between accuracy and complexity. Before dimensionality reduction, the algorithms demonstrated promising results, with RF exhibiting excellent AUC/ROC scores and average accuracy. However, computational costs were noted as a potential drawback for RF, especially when dealing with large datasets. EXT showcased robust performance and good accuracy, while XGboost demonstrated its ability to handle complex relationships within large datasets, albeit requiring careful hyperparameter tuning. The efficiency and scalability of LightGBM made it a suitable choice for large datasets, although it displayed sensitivity to class imbalance. Catboost excelled in handling categorical features, but longer training times were observed for larger datasets. NB showcased simplicity and computational efficiency but assumed independence among features. KNN, known for its capability to capture local patterns and spatial relationships, was found to be sensitive to the choice of distance metric. GBM, while capturing complex relationships effectively, was prone to overfitting without proper regularization. DT, with its interpretability and ease of understanding, faced limitations in terms of overfitting and limited generalization. After dimensionality reduction, certain algorithms exhibited improvements in their AUC/ROC scores and average accuracy, including RF, EXT, XGboost, and LightGBM. However, for a few algorithms, such as NB and DT, a decrease in performance was observed. This study provides valuable insights into the performance characteristics, strengths, and limitations of various machine learning algorithms in classification tasks. Researchers and practitioners can utilize these findings to make informed decisions when selecting algorithms for their specific datasets and requirements. We also aim to identify the potential factors contributing to the high accuracy rates obtained from these ensembled algorithms and explore possible shortcomings of non-ensembled algorithms that may result in lower accuracy rates. By conducting a comprehensive analysis of these algorithms, we seek to provide valuable insights into the benefits and limitations of ensembled approaches for landslide susceptibility mapping. Our study sheds light on the challenges faced when balancing accuracy and complexity in machine learning models for landslide susceptibility mapping. It emphasizes the importance of carefully considering the level of complexity and entropy reduction in relation to the specific patterns and uncertainties present in the data. By providing insights into this tradeoff, our research aims to assist researchers and practitioners in making informed decisions regarding model complexity and entropy reduction, ultimately improving the quality and interpretability of landslide susceptibility maps.

The province of Jaén (Andalusia, Spain), despite being declared the European territory with the largest number of defensive constructions (castles, fortifications, etc.), has few conservation plans, with many remains included on the Red List of Spanish Heritage ly-ing abandoned. This poses a challenge for landscape conservation and the optimal use of the province’s tourism potential. In this paper we present the early implementation of an ongoing methodological approach designed to alleviate this situation. It takes advantage of data from the Sentinel 2A and 2B satellites, HBIM, RPAS, GIS and fieldwork that will be applied across five archaeological case studies. It has been tested for the first time in the village of Magaña. Three main objectives and phases of this methodological approach have been designed: 1. Preparation of an Environmental Risk Chart with which to answer such ques-tions as “How have climate change, anthropic alterations and environmental characteris-tics affected the state of conservation of certain heritage sites?” 2. Preparation of HBIM models to foster monitorisation and conservation policies for the main archaeological remains and improving their protection based on digital and technological tools. 3. Building a Smart Tourism App for mobile devices aimed at promoting smart tourism by digitalising and virtualising tourist itineraries and archaeological remains. Finally, public administrations will be apprised of the need to implement a conservation policy for cultural assets and their surroundings in a simple, quick and cost-effective man-ner.

This article discusses the comparison between digital and traditional face-to-face coaching within the scope of shadow education institutions. While analyzing the differences and similarities between the two educational models, both their advantages and disadvantages are thoroughly discussed. In this context, interviews were conducted with students and teachers who receive education in both face-to-face and digital coaching, and the positive and negative aspects of both institutions, suitable and unsuitable courses, the future situation, and the effects on students' academic achievements were revealed. According to the results obtained from the research, it is noteworthy that students who do not receive education in digital coaching have prejudices against digitalization. Additionally, no significant difference was found between the academic achievements of students receiving education in digital coaching and those receiving education in face-to-face coaching.

The steady-state dissolution rates of basaltic glass and labradorite have been measured in the presence of 10 to 700 x 10-3 mol kgw-1 aqueous NaCl, KCl, CaCl2, and MgCl2 at 25 oC. All rates were measured in mixed flow reactors, and at pH~3.6 by the addition of HCl to the reactive fluids. Steady-state basaltic glass dissolution rates based on Si release increased by ~0.3 log units in the presence of 1 x 10-2 mol kgw-1 of CaCl2 or MgCl2, compared to their rates in 10 x 10-3 mol kgw-1 of NaCl, and KCl. In contrast, the steady-state dissolution rates of labradorite decreased by ~0.4 log units in the presence of 10 x 10-3mol kgw-1 of CaCl2 or MgCl2, compared to their rates in 10 x 10-3 mol kgw-1 of NaCl, and KCl. These contrasting behaviours likely reflect the varying effects of these cations on the stability of rate controlling Si-rich activated complexes on the surface of the solids. On average, the Si release rates of these solids are similar to each other and increase slightly with increasing ionic strength. As the pH of water charged with 10 to 30 bars CO2 is ~3.6, the results of this study indicate that both basaltic glass and labradorite dissolution will likely be effective at increasing pH and adding Ca to the aqueous phase in saline fluids. This observation supports potential efforts to store carbon through its mineralization in saline aquifers containing Ca-bearing feldspar and in submarine basalts.

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.

Abstract: The overuse of antibiotic prophylaxis during the COVID-19 pandemic would have led to the devel-opment of antibiotic-resistant bacterial strains, thereby increasing the epidemiological burden of antimicrobi-al resistance. The aim of this study was to determine the prevalence and antibiotic resistance pattern of bacte-ria isolated in 02 referral health facilities in Yaoundé before and during the COVID-19 pandemic era. We conducted a retrospective study over a period of 03 years (from 1 January 2019 to 31 December 2021) in the bacteriology units of the Central and General Hospitals of Yaoundé, Cameroon. The review of the services' registers was done to record bacterial isolates (Streptococcus, Staphylococcus, Neisseria meningitidis and Entero-bacteriaceae) as well as their susceptibility to selected, specific and highly potent antibiotics: Cefixime, Azythromycin and Erythromycin. The relationship between each group of resistant bacteria and the antibiotic of interest was determined by simple linear regression; the comparison of the prevalences of before (2019) and during 2 consecutive years of the COVID-19 pandemic onset (2020 and 2021) was done by the Chi2 test of in-dependence. In all, 426 bacterial strains were included. It appeared that the highest number of bacteria iso-lates and lowest rate of bacterial resistance were recorded during the pre-COVID 2019 period in 2019 (160 isolates vs. 58.8% resistance rate). Conversely, lower bacteria stains but greater resistance burden were rec-orded during the pandemic era (2020 and 2021) with the lowest bacteria amount and peak of bacteria re-sistance registered in 2020, the year of COVID-19 onset (120 isolates vs. 70% resistance in 2020 and 146 iso-lates vs.58.9% resistance in 2021). In contrast to almost all others groups of bacteria where the resistance burden was quite constant over years, the Enterobacteriaceae exhibited greater resistance rate during the pandemic period [60%(48/80) in 2019 to 86.9%(60/69) in 2020 and 64.5%(61/95) in 2021)]. Concerning antibiotics, unlike Erythromycin, Azythromycin related resitance increased during the pandemic period and the resistance to Cefixim tends to decrease the year of the pandemic onset (2020) and re-increase one year therafter. A significant association was found between resistant Enterobacteriaceae strains and Cefixime (R= 0.7; P-value= 0.0001) and also, between resistant Staphylococcus strains and Erythromycin (R= 0.8; P-value= 0.0001). It could be that the more frequent use of these antibiotics has increased resistance rate especially in Enterobacteriaceae. Anticromicrobial resistance should be closely monitor during and after COVID pandemic era.

The province of Jaén (Andalusia, Spain), despite being declared the European territory with the largest number of defensive constructions (castles and fortifications), has few conservation plans, with many remains included on the Red List of Spanish Heritage lying abandoned. This presents a problem for the conservation of the landscape and the optimal use of the province’s tourism potential. Through the study case of Magaña hamlet two actions are proposed to alleviate this situation: The creation of an archaeological and environmental risk chart with which to answer such questions as “How have climate change, anthropic alterations and environmental charac-teristics affected the state of conservation of certain heritage sites?” and to put forward proposals for improving their protection using as a basis digital and technological tools, such as remote sensing (SAR), taking advantage of data from the Sentinel 2A and 2B satellites, HBIM, RPAS and GIS. To foster the promotion of smart tourism by digitalising and virtualising tourist routes and archaeological remains by building a Smart Tourism App for mobile devices. Finally, public administrations will be apprised of the need to implement a conservation policy for cultural as-sets and their surroundings in a simple, quick and cost-effective manner.

An important step towards COVID-19 pandemic control is adequate knowledge and adherence to mitigation measures, including vaccination. We assessed the level of COVID-19 knowledge, attitudes, and practices among residents from an urban informal settlement in the City of Nairobi (Kibera), and a rural community in western Kenya (Asembo). A cross-sectional survey was implemented from April to May 2021 among randomly selected adult residents from a population-based infectious diseases surveillance (PBIDS) cohort in Nairobi and Siaya Counties. Factors associated with the level of COVID-19 KAP, were assessed using multivariable regression methods. COVID-19 vaccine acceptance was 83.6% for the participants from Asembo and 59.8% in Kibera. The reasons cited for vaccine hesitancy in Kibera were safety concerns (34.0%), insufficient information available to decide (18.0%), and a lack of belief in the vaccine (21.0%), while the reasons in Asembo were safety concerns (55.0%), insufficient information to decide (26.0%) and lack of belief in the vaccine (11%). Our study findings suggest the need for continued public education to enhance COVID-19 knowledge, attitudes, and practices to ensure adherence to mitigation measures. Urban informal settlements require targeted messaging to improve vaccine awareness, acceptability, and uptake.

Abstract: (1) Background: tuberculosis presents an epidemiological trend towards inequality, especially among people in social exclusion and situations of vulnerability. To analyze territories where there is a concentration of people diagnosed with tuberculosis, in a street situation, and who make chronic use of alcohol, tobacco, and illicit drugs. We will also analyze trends in this health condition in southern Brazil; (2) Methods: Ecological study, developed in the 399 municipalities of Paraná, Southern Brazil, with all tuberculosis cases in the homeless population registered in the Information System of Notifiable Diseases between 2014 to 2018. For data analysis, we used descriptive statistics, for the time series, the Prais-Winsten autoregression method, whereas for spatial analysis, we used the Getis-Ord Gi technique*; (3) Results: in total, 560 cases were reported. We found a predominance of alcohol, smoking, and illicit drugs users, with an increasing trend in the state and clusters of spatial risk in the East health macro-region; (4) Conclusions: We observed territories with critical levels of highly vulnerable people who use psychoactive substances and are in a street situation. The results highlight the importance of incorporating public policies of social protection to these individuals and resolutive health services that receive and assist in eradicating TB.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory (CIRS) systems and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AF-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of the disease. However, the interactome of FEP/FES is not well delineated. The aim of the current study was to delineate the characteristics of the protein-protein interaction (PPI) network of AN-FEP and its transition to FES and the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. PPI network analysis shows that FEP and FEP/FES are strongly associated with a response to a bacterium, TNF, NFκB, RELA, SP1, JAK-STAT, death receptor and TLR4 signaling, and tyrosine phosphorylation of STAT proteins. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin/Trk, RTK and Wnt/catenin signaling and adherens junction organization. Lowered neuroprotection due to reduced neurotrophin/Trk and Wnt/catenin signaling, and DISC1 expression and multiple interactions between lowered BDNF, CDH1, CTNNB, and DISC1 expression, increase the vulnerability to the neurotoxic effects of immune products including cytokines and complement factors. All pathways or molecular patterns enriched in the interactome of FEP/FES are directly or indirectly affected by LPS. In summary: FEP appears to be triggered by a biotic stimulus (e.g. Gram-negative bacteria) which may induce neuro-immune toxicity cascades especially when anti-inflammatory and neurotrophic protections are deficient.

Background. COVID-19 patients suffer from hypercoagulation and activated immune-inflammatory pathways. This study was performed to assay serum complement C3 and C4, and thromboxane A2 (TxA2) and prostacyclin (PGI2) in association with chest CT scan anomalies (CCTAs) and peripheral oxygen saturation (SpO2) Methods. Serum levels of C3, C4, TxA2, and PGI2 were measured by ELISA and albumin, calcium, and magnesium by spectrophotometric method in 60 COVID-19 patients and 30 controls. Results. C3 and C4 are significantly decreased and TxA2 and PGI2 significantly increased in COVID-19 patients as compared with controls. Neural networks showed that a combination of C3, albumin, and TxA2 yielded a predictive accuracy of 100% in detecting COVID-19 patients. SpO2 was significantly decreased in COVID-19 patients and was inversely associated with TxA2 and PGI2, and positively with C3, C4, albumin, and calcium. CCTAs were accompanied by lower SpO2 and albumin, and increased PGI2 levels. Patients with positive IgG results show significantly higher SpO2, TxA2, PGI2, and C4 levels than IgG negative patients. Conclusion. Hypoalbuminemia, which is strongly associated with lung lesions and lowered peripheral oxygen saturation, is characterized by increased TxA2, suggesting that interactions between immune-inflammatory pathways and platelet hyperactivity participate in the pathophysiology of COVID-19 and consequently may play a role in enhanced risk of hypercoagulability and venous thromboembolism. These mechanisms are aggravated by lowered calcium and magnesium levels.

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls.Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO₂ and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

Digital technologies have changed the way supply chain operations are structured. In this article, we conduct systematic syntheses of literature on the impact of new technologies on supply chains and the related cyber risks. A taxonomic/cladistic approach is used for the evaluations of progress in the area of supply chain integration in the Industrial Internet of Things and Industry 4.0, with a specific focus on the mitigation of cyber risks. An analytical framework is presented, based on a critical assessment with respect to issues related to new types of cyber risk and the integration of supply chains with new technologies. This paper identifies a dynamic and self-adapting supply chain system supported with Artificial Intelligence and Machine Learning (AI/ML) and real-time intelligence for predictive cyber risk analytics. The system is integrated into a cognition engine that enables predictive cyber risk analytics with real-time intelligence from IoT networks at the edge. This enhances capacities and assist in the creation of a comprehensive understanding of the opportunities and threats that arise when edge computing nodes are deployed, and when AI/ML technologies are migrated to the periphery of IoT networks.

Digital technologies have changed the way supply chain operations are structured. In this article, we conduct systematic syntheses of literature on the impact of new technologies on supply chains and the related cyber risks. A taxonomic/cladistic approach is used for the evaluations of progress in the area of supply chain integration in the Industrial Internet of Things and Industry 4.0, with a specific focus on the mitigation of cyber risks. An analytical framework is presented, based on a critical assessment with respect to issues related to new types of cyber risk and the integration of supply chains with new technologies. This paper identifies a dynamic and self-adapting supply chain system supported with Artificial Intelligence and Machine Learning (AI/ML) and real-time intelligence for predictive cyber risk analytics. The system is integrated into a cognition engine that enables predictive cyber risk analytics with real-time intelligence from IoT networks at the edge. This enhances capacities and assist in the creation of a comprehensive understanding of the opportunities and threats that arise when edge computing nodes are deployed, and when AI/ML technologies are migrated to the periphery of IoT networks.

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

Fertility management techniques being promoted in sub-Saharan Africa (SSA) seek to grow indigenous vegetables economically and sustainably. This study was conducted in a phytotron chamber and compared yield, soil carbon (C) speciation and greenhouse gas (nitrous oxide (N₂O) and carbon dioxide (CO₂)) emissions from SSA soils of two ecoregions; the dry savanna (lna, Republic of Benin) and rainforest (Ife, Nigeria) cultivated with local amaranth (Amaranthus cruentus) under manure (5 t/ha) and/or urea (80 kg N/ha) fertilization. Vegetable yield ranged from 1753 kg/ac to 3198kg/ac in the rainforest, RF, soils and 1281 kg/ac to 1951 kg/ac in the dry savanna, DS, soils. Yield in the urea treatment was slightly higher compared to the manure+urea treatment, but the difference was not statistically significant. Cumulative CO₂ emissions over 21 days ranged from 497.06 to 579.47 g CO₂ in the RF, and 322.96 to 624.97 g CO₂ in the DS, while cumulative N₂O emissions ranged from 60.53 to 220.86 mg N₂O in the RF, and 24.78 to 99.08 mg N₂O in the DS. In the RF samples, the combined use of manure and urea reduced CO₂ and N₂O emissions but led to an increase in the DS samples. ATR-FTIR analysis showed that the combined use of manure and urea increased the rate of microbial degradation in the soils of the DS, but no such effect was observed in soils of the RF. We conclude that combining manure and urea fertilization has different effects on soils of the two ecoregions, and that RF farmers can reduce agricultural emissions without compromising soil productivity and yield potential.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.

This study presents the validation process of the Questionnaire on Academic Stress in Secondary Education –QASSE-, designed to assess the wide variety of school sources and situations related to academic stress in adolescence, and their relationship with students’ physical and psychological well-being. Participants were 860 Spanish high school students (52.9% girls) with an average age of 14.62 years (SD = 1.8). Through a cross-validation process, EFA and CFA supported QASSE multifactorial structure with four first-order factors -academic overload, interaction with classmates, family pressure, and future-oriented perspective- and a second-order factor of academic stress, showing a significant and intense relationship with adolescents’ psychological and physical well-being. Results also highlight the effects of the gender*educational level interaction on the students’ stress, with girls showing higher levels of stress in the transition courses between educational phases (sophomore and junior years). The QASSE demonstrates good validity and reliability, showing potential for both research and educational application. The results show the high impact of the QASSE dimensions on psychological and physical well-being in adolescence, highlighting its special usefulness for designing and adjusting educational prevention and intervention actions in this area to the students’ specific characteristics and needs

In addition to its use as a food additive, sesame is also very popular in conventional drugs because of its antifungal, anticancer, analgesic, antioxidant, and antiproliferative, vitamin B and E supplier, serum cholesterol and blood pressure-lowering, wound healing potential. In this study, the cytotoxicity, wound healing, and anticancer (antiproliferation) properties of the ex-tract obtained from in vitro cultures of Sesamum orientale L. cv. "Gökova" were investigated using in L929 fibroblast, MCF-7 breast, and A549 lung epithelial cell lines. In our study, the cisplatin was also used as a control group to compare the anticancer efficacy of our plant extract. The IC50 values obtained from cell treatments were 922.73 µg.ml-1 (plant extract) and 33.09 µg.ml-1 (cispla-tin) for A549 µg.ml-1, 1837.07 µg.ml-1 (plant extract) and 19.27 µg.ml-1 (cisplatin) for MCF-7, and 154.70 µg.ml-1 (plant extract) for L929, respectively. The subcytotoxic doses of the treated plant extract provided the healing of artificially created wounds on L929 fibroblast cell cultures within 48 hours. For the evaluation of the anticancer activity, it was also determined that transcriptomic analyzes of BCL-XL gene, which is negatively correlated with apoptotic pathway, and Cas3 and Cas9 genes, which are positively correlated with apoptotic pathway, showed a statistically sig-nificant increase in A549 and MCF-7 cell lines treated with plant extract or cisplatin. In the light of the results obtained from the present study, it was seen that sesame plant extract may have wound healing potential at decreasing doses and anticancer activity potential at increasing dos-es. The present study can be a useful resource for the development of a drug with wound healing and/or antiproliferative potential, with applications to be made in different cell lines in the future.

How the subculture and marginalized community have become the leading sectors in the egalitarian and inclusive creative economy is a growing issue and still needs elaboration. One of the subculture phenomena that happened recently in one of Southeast Asia's countries is known as Citayam Pop-up and Makeshift Fashion Week (CFW). Then this paper aims to elaborate on how the CFW can contribute and play a significant role in the development of an egalitarian and inclusive creative economy. The current CFW was not developed instantly, yet it is through the complexities of push and pull factors that are very typical among SE Asian marginalized people that led to the onset of SE Asian subculture, particularly among the youth. Driven by finding their self-identity, wanting to belong, and combined with economic, family, and peer pressures, this group of suburban youth, at the beginning, find a corner of a city in the middle of the business district as a medium to express their identity in the form of CFW. As a result and in lieu of growing discourses, the CFW has boosted local economic growth, and the adolescents who participated in the CFW have also received endorsement from a startup business for marketing certain teen products. In the long term, the mutual relationships created can lead to job opportunities

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

Developing short-term forecasting model for global atmospheric temperature and wind in the near space is crucial for understanding atmospheric dynamics and supporting human activities in this region. While numerical models have been extensively developed, deep learning techniques have recently shown promise in improving atmospheric forecasting accuracy. In this study, convolutional long short-term memory (ConvLSTM) and convolutional gated recurrent unit (ConvGRU) neural networks were applied to build for short-term global-scale forecasting model of atmospheric temperature and wind in the `near space based on the MERRA-2 reanalysis dataset from 2010-2022. The model results showed that the ConvGRU model outperforms the ConvLSTM model in the short-term forecast results. The ConvGRU model achieved a root mean square error in the first three hours of approximately 1.8 K for temperature predictions, and errors of 4.2 m/s and 3.8 m/s for eastward and northward wind predictions, respectively.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas, the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). We, for the first time, have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Many studies have demonstrated hydrogen's therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. Sub-lethal WBI resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of lethal WBI, while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

Much evidence now indicates a direct crosstalk between thyroid hormones (THs) and the immune system. We previously showed that THs behave as anti-inflammatory agents in human leukemic THP-1 monocytes, but a potential neuroprotective effect of THs in microglia have been under-investigated. Microglia, the primary innate immune cells of the brain, play a pivotal role in the regulation of neuroinflammation and nongenomic integrin αvβ3-mediated action of THs appear to be involved. Integrin αvβ3 was highly expressed in activated BV-2 cells, while it was decreased by THs. In addition, THs facilitated wound healing in BV-2 murine microglia cells activated by lipopolysaccharide (LPS), through integrin αvβ3 and reactive oxygen species (ROS), with tetrac (a metabolite of TH) potentiated the inhibition of migration. Nitric oxide (NO) played a role with different mechanisms in the presence of either T3 or T4. Our data showed the capability of TH and analogues to modulate the M1-to-M2 microglial transition and suggest a new spectrum of actions in the central nervous system (CNS).

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Green peppers (Capsicum annuum L.) is a fruit vegetable with great culinary versatility, and present important nutritional properties for human health. Water deficit negatively affects nutritional quality of green peppers fruits. This study aimed to investigate the influence of zinc oxide nanoparticles (ZnONPs), associated with plant growth-promoting bacteria (PGPB), on the post-harvest quality nutritional of green peppers subjected to water deficit. In an open-field ex-periment, two irrigation levels (50 and 100% of crop evapotranspiration - Etc), four treatments composed by combination of ZnONPs, zinc sulfate (ZnSO4) and PGPB (T1 = ZnSO4, T2 = foliar ZnONPs, T3 = foliar ZnONPs + PGPB, T4 = ZnSO4 via soil + PGPB via soil) and a control treatment (Check) were tested. Water deficit or water deficit mitigation treatments did not interfere with the physical-chemical parameters (except vitamin C content) and physical color parameters (except L*) of green pepper. The water deficit reduced the levels of Ca, Mg, P, K, Mn, Fe, B, and Zn in the fruits. The foliar application of ZnONPs in association with PGPB provided better nutritional quality of green pepper in terms of vitamin C and mineral nutrients. Under water deficit, ZnONPs or ZnSO4 via foliar, associated or not with PGPB, increased the levels of Ca, P, Mg, and Fe in the fruits. Applying Zn via foliar as ZnONPs or ZnSO4 mitigated the negative effects of water deficit on the quality of pepper fruits that was enhanced by the Bacillus subtilis and B. amyloliquefaciens inoculation.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from July 1, 2020, to August 31, 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71%(79) of patients underwent an EGD within 6 months, revealing varices in 41%(32) and requiring intervention in 19%(15). The overall bleeding rate was 15%(17), with GI-specific bleeding occurring in 83%(5) of the EGD group and 17%(1) of the non-EGD group (p=0.24). Non-GI bleeding was observed in 10%(11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. Our study showed twice the rate of varices detection and treatment compared to IMbrave150, reflecting real-world treatment of high-risk populations. There was no increased GI bleeding in patients without pre-treatment EGD, supporting a selective EGD approach.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of modified RoPE score for PFO presence in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without PFO (median 63 years vs. 71 years, p&lt;0.001) and fewer were female (46.1% vs. 49.7%, p&lt;0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p&lt;0.001). The area under the curve for the RoPE score in predicting PFO was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut point of ≥5 increased specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFO was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

Rutin, a flavonoid compound found in various plants, has gained attention for its potential applications in the cosmetic industry due to its antioxidant, anti-inflammatory, and potential photoprotective properties. Our review explored the use of rutin (rutoside, 3-O-rutinoside-quercetin) in cosmetics/dermocosmetics, focusing on its physicochemical properties and stability, cutaneous permeability, and efficacy in sunscreen systems, involving in vitro tests and the current state of clinical trials. Rutin's ability to scavenge free radicals, prevent peroxidation, and reduce vascular fragility makes this flavonoid a promising ingredient for photoprotection. Studies have shown that rutin can enhance the sun protection factor (SPF) of sunscreen formulations, especially when combined with organic UV filters. The encapsulation of rutin in nanostructures has also been investigated to improve its applicability. Overall, rutin shows potential as a safe and effective ingredient in cosmetic/dermocosmetic formulations, offering protection against the harmful effects of UV radiation and oxidative stress on the skin.

Image-guided radiotherapy supported by surface guidance can help track lower lung lesion respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how skin respiratory motion magnitudes and correlations with lung lesion respiratory motion vary between different skin regions of interest (ROI). Four-dimensional Computed Tomography (4DCT) images provide information on both skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. Analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing lower lung lobe lesion, as well as respiratory motion correlations between nine ROIs and TS. The effects of gender and adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between ROIs in both respiratory motion magnitudes and correlations to TS have been detected. An overall negative correlation between ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. Respiratory magnitudes in regions without rib support tended to be larger for men than for women, but no differences in ROI-to-TS correlation between sexes have been detected. Described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

1) Background: carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic Gram-negative pathogen that has a significant role in healthcare-associated infections. Unlike several studies on the antibiotic-resistant epidemiology of A. baumanni, virulence molecular epidemiology was less studied. This study aimed to investigate CRAB virulence genes and their ability to form biofilms, and to correlate their biofilm formation ability with both; biofilm-encoding virulence genes and carbapenemase-encoding resistance genes. 2) Methods: 107 CRAB clinical isolates were collected from two hospitals in Jordan between 2018 and 2019 and were screened for virulence genes using PCR. In addition, biofilm formation ability was assessed using the microtiter plate method. 3) Results: the frequencies of the bap, OmpA, surA, PLD, paaE, basD, and traT virulence genes were 99.10%, 98.20%, 98.20%, 95.50%, 89.10%, 86.40%, and 8.20%, respectively. Overall, 86.4% of the tested isolates were biofilm formers with varying degrees; weak (28.2%), moderate (36.4%) and strong (21.8%). A significant relationship was found between the carbapenemase-encoding gene (OXA-23 gene) and biofilm production. 4) Conclusion: to the best of our knowledge, this is the first study in Jordan that inspected CRAB virulence genes and highlighted the importance of improving infection control measures to avoid CRAB outbreaks.

This article aimed to evaluate, using statistical tools, the generation and composition of urban solid waste (MSW) in the city of Belém, Pará, from nine urban collection sectors in the municipality, and the average nominal income of the population. Approximately 900kg of urban solid waste were col-lected from the municipality in the period from 2021 to 2022. Statistical tests were carried out on hypotheses with 5% significance in comparative evaluations, and their respective average nominal incomes. The results indicated that the organic fraction corresponds to 55.57% of the waste generated in the municipality, 14.26% is inert waste (potentially contaminating) and 0.67% is miscellaneous waste. It was observed that the waste generated by families with high purchasing power tends to contain higher percentages of recyclables, while in families with lower purchasing power the highest percentages tend to be organic. Knowledge of the generation of MSW is fundamental for the choice and dimensioning of operations and processes involved in the management chain at the municipal level. The decentralization of services offered based on solid waste management would enable greater success in serving the population.

In clinical practice, patient assessments rely on established scales. Integrating data from these scales into the International Classification of Functioning, Disability, and Health (ICF) framework has been suggested; however, a standardized approach is lacking. Herein, we tested a new approach to develop a conversion table translating clinical scale scores into ICF Qualifiers based on a clinician survey. The survey queried rehabilitation professionals about which functional independence measure (FIM) item scores (1-7) corresponded to the ICF qualifiers (0-4). A total of 458 rehabilitation professionals participated. The survey findings indicated a general consensus on the equivalence of FIM scores with ICF qualifiers. The median value for each item remained consistent across all item groups. Specifically, FIM 1 had a median value of 4; FIM 2 and 3 had median values of 3; FIM 4 and 5 had median values of 2; FIM 6 had a median value of 1; and FIM 7 had a median value of 0. Despite limitations due to the irreconcilable differences between the frameworks of existing scales and the ICF, these results underline the ICF's potential to serve as a central hub for integrating clinical data from various scales.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU) grew within a colloidal suspension of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers MA and ME, respectively). This method, applied for the first time in Semi Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality, since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a twenty-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. ME-based PHU exhibited higher (M_w ) ̅ than MA-based PHU (34,100 Da and 16,400 Da, respectively). Applying the enhanced methodology to prepare ten multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating ME enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when MA was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

A sustainable green one pot procedure for the synthesis of dihydropyrimidinones (DHPMs) derivatives by a three-component reaction of β-ketoester derivatives, aldehyde and urea or thiourea over the alkali-treated H-ZSM-5 zeolite under ball-milling has been developed. The product was isolated by simple washing of the crude reaction residue with ethyl acetate followed by evaporation of solvent. The hierachical zeolite catalyst (MFI27_6) showed high yield (86–96%) of dihydropyrimidinones (DHPMs), in very short time (10-30 min). The catalyst is recycled for subsequent reactions in four runs without appreciable loss of activity and high yields of products provide efficient protocol for Biginelli reactions.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

This research investigates the relationship between the long-term orientation of top managers and their strategic decision-making processes, emphasising the comprehensiveness, speed, and inventiveness of decisions. The study employed structural equation modelling to look into the suggested connections using a sample of CEOs. The findings demonstrated a high and positive correlation between long-term orientation and decision comprehensiveness and speed, but not for decision creativity. The study contributes to the growing body of research on how human variations, such as temporal orientation, affect business outcomes and strategic decision-making. Moreover, the fact that a number of the results differed from those of other studies carried out in other contexts highlights how important it is to consider the industry and cultural environment when assessing these connections.

Over the coming decades, global freshwater withdrawals are expected to grow, especially in low and middle-income countries. Unless there are significant improvements in the efficiency of water use by economies, freshwater stress, crises and scarcity will worsen. This paper explores further the economic relationship between water use efficiency and scarcity. Because growing scarcity of freshwater in many regions and countries is not adequately reflected in markets, there is often insufficient incentives for investment and innovation to improve the efficiency of water use. To explore further changes in water use efficiency across countries, we conduct a panel analysis of water productivity changes for 130 countries over 1995 to 2020. Countries with lower initial levels of water use efficiency tended to have higher water productivity growth, whereas more agriculturally dependent economies displayed lower improvements in water use efficiency. Better institutional quality and capacity for innovation may also increase water use efficiency. We discuss the implications of these results for improving water use productivity in economies, and in particular, the opportunities and challenges for improving water markets and trades to alleviate water scarcity. We conclude by identifying further areas of research.

Objectives: The tau protein is essential for stabilizing microtubules. Changes in its phosphorylation are identified in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. The hyperphosphorylation of the tau protein is linked to various factors, including stress, which has a substantial impact on depressive illness. The present study aimed to systematically review studies that describe the association between tau protein and depression.Design: The present study used the PRISMA statement 2020 as the inclusion criterion for articles describing tau protein in individuals with depression. The exclusion criterion was the lack of comparison of tau protein levels with individuals without depression.Results: A total of 138 papers were identified, of which 21 were ultimately included. One out of every three articles included demonstrated the statistical significance of the tau protein values between the depression group and controls. Only one had an adequate sample but demonstrated results without any major significance.Conclusions: The association between tau protein and depression remains unclear. Studies with adequate sampling are necessary to answer this question.

This article reviews all the major stages in the origins of life. From the emergence of matter in the initial Big Bang to the modern, civilized human being. On an immaterial level, it is proposed and explained how consciousness necessarily takes precedence over matter. Next, we explain how consciousness, with its ability to process information, selected the water molecule to breathe life into the periodic table of elements. We also explain why the notion of entropy allows us to evolve: "Die Entropie der Welt strebt einem Maximum zu" (second principle) and, therefore, takes precedence over the notion of energy, which, on the contrary, encourages us to preserve what we have: "Die Energie der Welt bleibt konstant" (first principle). This is followed by a discussion of the importance of quantum coherence and the need to rely on a second quantization formalism for a proper understanding of the physical-biochemical properties of water. Moreover, throughout the argument developed on the best and most fundamental things science has to offer, care is taken to link this knowledge to the great philosophies of the West (Greece), the East (China, India) or even to practices of a shamanic nature (Africa, America). Hence, finally, the proposal to reconsider all musical practice within the framework of the diapason of water at a frequency of 429.62 Hz, as well as all therapeutic practice on the basis of seven clearly identified and established frameworks of thought.

Information theoretic quantities such as entropy, entropy rate, information gain, and relative entropy are often used to understand the performance of intelligent agents in learning applications. Mean squared error has not played a role in these analyses, primarily because it is not felt to be a viable performance indicator in these scenarios. We build on a new quantity, the log ratio of entropy powers, to establish that minimum mean squared error (MMSE) estimation, prediction, and smoothing are directly connected to Mutual Information Gain or Loss in an agent learning system modeled by a Markov chain for many probability distributions of interest. Expressions for mutual information gain or loss are developed for MMSE estimation, prediction, and smoothing and an example for fixed lag smoothing is presented.

This study examines a new approach to hybdrid neuromorphic devices by studying the impact of omeprazole-proteinoid complexes on Izhikevich neurone models. We investigate the influence of these metabolic structures on five specific patterns of neuronal firing: accommodation, chattering, triggered spiking, phasic spiking, and tonic spiking. By combining omeprazole, a proton pump inhibitor, with proteinoids, we create a unique substrate that interfaces with neuromorphic models. The Izhikevich neurone model is used because it is computationally efficient and can accurately simulate various behaviours of cortical neurones. The results of our simulations show that omeprazole-proteinoid complexes have the ability to affect neuronal dynamics in different ways. This suggests that they could be used as adjustable components in bio-inspired computer systems. We have noticed a notable alteration in the frequency of spikes, patterns of bursts, and rates of adaptation, especially in chattering and triggered spiking behaviours. The findings indicate that omeprazole-proteinoid complexes have the potential to serve as adaptable elements in neuromorphic systems, presenting novel opportunities for information processing and computation that have origins in neurobiological principles. This study makes a valuable contribution to the expanding field of biochemical neuromorphic devices and establishes a basis for the development of hybrid bio-synthetic computational systems.

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homologue, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives of the study of NOXs in CVDs.

The global need for rapid diagnostic methods for pathogen identification and antimicrobial susceptibility testing (AST) is underscored by the increasing bacterial resistance and limited therapeutic options, especially critical in sepsis management. The evolution from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly decreased result turnaround times, improving patient outcomes. Despite advancements, the complex decision-making in antimicrobial therapy often exceeds the capacity of many clinicians, highlighting the importance of antimicrobial stewardship programs (ASP). These programs, integrating mHealth and eHealth, leverage technology to enhance healthcare services and patient outcomes, particularly in remote or resource-limited settings. However, the application of such technologies in antimicrobial management remains underexplored in hospitals. The development of platforms combining antimicrobial prescription data with pharmacotherapeutic algorithms and laboratory integration can significantly reduce costs and improve hospitalization times and mortality rates. Yet, the effectiveness of empirical antibiotic therapy, influenced by rapid diagnostic tests, becomes cost-effective when error rates exceed 20%, emphasizing the need for technological integration in ASPs to combat the rising challenge of antimicrobial resistance (AMR) and healthcare sustainability.

The purpose of this narrative review is to provide an overview of the latest literature on bariatric and metabolic surgery for diabetes mellitus type II and obesity (diabesity) and to discuss its implications for future research and clinical practice.

The scientific fields of complexity, artificial life (ALife), and artificial intelligence (A.I.) share commonalities: historic, conceptual, methodological, and philosophical. Although their origins trace back to the 1940s birth of cybernetics, they were only able to properly develop as modern information technology became available. In this perspective, I offer a personal (and thus biased) account of the expectations and limitations of these fields, some of which have their roots in the limits of formal systems. I will use interactions, self-organization, emergence, and balance to compare different aspects of complexity, ALife, and A.I. Even when the trajectory of the paper is influenced by my personal experience, the general questions posed (which outweigh the answers) hopefully will be useful to align efforts in these fields toward overcoming --- or accepting --- their limits.

There is a lot of pressures from organizations to continually redesign the business processes and the technology infrastructure to support the organization, but to also help organizations manage competing stakeholder needs, changing objectives and behaviour, and so on. A key part of this is making sure that all their activities in the different components of the business are interconnected and that they are moving in the same direction. Enterprise Architecture (EA) is an effective way of dealing with the challenge of designing business activities and supporting IT. This paper will summarize the organization of EA and look more closely at some major components of EA: governance architecture, business architecture, information architecture and technical architecture and consider the overlap and constructive interaction involved. Enterprise Architecture can be best understood through business process redesign. So, it is useful to briefly review the leading frameworks for business process redesign, including COBIT from ISACA, LEAN from the Toyota Group, TOGAF from the Object-Management Group, and the Capgemini Integrated Architecture Framework (IAF). All these frameworks allow us to more successful transformation, to return to the central idea of this paper.

Linear Hashing is an important algorithm for many key-value stores. Spiral Storage was invented to overcome the poor fringe behavior of Linear Hashing, but after an influential study by Larson, seems to have been discarded. Since almost 50 years have passed, we repeat Larson’s comparison with in-memory implementation of both to see whether his verdict still stands. Our study shows that Spiral Storage has slightly better look-up performance, but slightly poorer insert performance.

The advanced industrial systems are characterized by complex event-driven processes. The specification and computer analysis are illustrated by the common problem of a servo drive with the PWM controller. A mathematical model from the class of Cauchy problems with non-liner control logic is presented to resolve the task discussed. The designed model is performed in two stages: the mathematical model specification (modeling) and implementation (simulation). Two approaches to make a model specification are considered, the first one is the traditional structural technique, and the advanced method is based on the finite state machine paradigm. Structural and finite state software models are built in progressive simulation tools. Computer implementation of the software models of hybrid systems is performed using platform built-in libraries with numerical methods and algorithms for correct event detection. The results of computational experiments for transient processes of phase variables are qualitatively identical, that proves the adequacy of the developed models. The algorithm for asymptotic event detection is considered in detail. This technique demonstrated the best results by the one-sidedness criterion, which is explained by using the author’s algorithm for the integration step determining and the event function dynamics monitoring in the vicinity of the event limits.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

We examine the relation between environmental, social, and governance commitment levels (ESG) and firm dividend payer status. Given that larger and more profitable firms are positively associated with both payer status and ESG, it could be that ESG and dividends are complements. However, given that both dividends and ESG relate to firm spending decisions, it may be that the choice is “either/or” and that ESG and dividends are substitutes. We document a positive relation between ESG and dividend payer status in U.S. firms over the period 1991-2016. In particular we find that the proportion of dividend payers is roughly 13% higher for firms with positive ESG compared to those with negative ESG. Including ESG in the models used to predict payer status provides, on average, a nearly 26% improvement in relative forecast accuracy. Our results are robust to estimation techniques and the inclusion of variables known to be determinants of payer status.

The power of movement in plants” by Charles Darwin details many examples of oscillatory growth exemplified more recently at the single cell level by pollen tube tip oscillations and associated ion fluxes, particularly Ca²⁺and H⁺. That implies an underlying growth oscillator based on the recent discovery that classical AGPs bind Ca²⁺ at the cell surface. The juxtaposition of AGPs with three other components embedded in the plasma membrane is evidence of a Ca²⁺ cycle that generates cytosolic Ca²⁺. It involves Ca²⁺ channels, auxin efflux “PIN” proteins and an auxin-activated proton pump that dissociates AGP-Ca²⁺ on demand. While the apparent simplicity of this system satisfies Occam’s Razor its hypothetical role as a global growth oscillator demands rigorous experimental appraisal. The wide ramifications extend from pollen tubes to stomatal guard cells. Stomata act as crucial components of a water hypercycle that contributes to homeostasis of a warming planet by regulating evaporative cooling, reflective cloud cover generated by vast forests and the high albedo of snow-capped mountains including polar ice-caps . The Gaia hypothesis of James Lovelock and Lynn Margulis is a brilliant metaphor.

Origin, mechanics and properties of the Solar System are analysed in the framework of the Complete Relativity theory (by the same author). According to Complete Relativity, everything is relative. Any apparent absolutism (notably invariance to scale of dimensional constants, absolute elementariness, invariance to time) is an illusion stemming from limits imposed by [or on] polarized observers that will inevitably lead to misinterpretation of phenomena (another illusion) occurring on non-directly observable scales or even on observable but distant scales in space or time. If everything is relative, reference frames will exist where particles are planets and where planets are living beings. Earth is, therefore, analysed here in more detail, both as a particle and, as a living evolving being (of, hypothesized, extremely introverted intelligence). The analysis confirms the postulates and hypotheses of the theory (ie. existence of discrete vertical energy levels) with a significant degree of confidence. During the analysis, some new hypotheses have emerged. These are discussed and confirmed with various degrees of confidence. To increase confidence or refute some hypotheses, experimental verification is necessary. Main conclusions that stem from my research and are further confirmed in this paper are: universes are, indeed, completely relative; Solar System is a scaled (inflated, in some interpretations) Carbon isotope with a nucleus in a condensed (bosonic) state and components in various vertically excited states; life is common everywhere, albeit extroverted complex forms are present on planetary surfaces only during planetary neurogenesis; anthropogenic climate change is only a part (trigger from one perspective) of bigger global changes; major extinction events on a surface of a planet are relative extinctions, a regular part of transformation and transfer of life in the process of planetary neurogenesis.

Structural and functional asymmetries are traceable in every form of life and, at all cases, are a phenomenon of homology. Functionally speaking, the division of labour between the two halves of the brain is a basic characteristic of the nervous system that arose even before the appearance of vertebrates. The most prominent consequence of this specialization in humans and animals is handedness. Even if handedness is far more commonly associated with the presence of a nervous system, it is also observed in aneural organism such as plants. To date, little is known regarding the possible functional significance of handedness in plants, and many questions remain open (among these, whether it reflects a generalized behavioural asymmetry). Here, we propose a comparative perspective to the study of handedness, including plants, by taking advantage of the experimental models and paradigms already used to study laterality in humans and various animal species. By taking this approach, we aim to enrich our knowledge on the concept of handedness across natural kingdoms.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular (CVD) disease not only due to multiple shared pathologic elements, but also because changes that develop over decades in CVD disease appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol, however, cholesterol dependent signaling such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase is downregulated indicating a cholesterol deficit with upregulation of cholesterol synthesis and efflux. Hypoxia related signaling in preeclampsia also appears paradoxical with increased Hypoxia Inducible Factors (HIF) in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol dependent signaling may arise from the effects of dietary lipid variance causing the cellular hypoxia which characterizes preeclampsia.

This article conducts a bibliometric analysis focusing on the influence of globalization and technology in the academic context. Previous studies have focused on analyzing the relationship between the number of research citations and international collaboration, but no study has explored it in the scope of consumer behavior and retail. Leveraging the Scopus database, the research analyzes a significant corpus of 2,111 documents from 1971 to 2022. The findings reveal a distinct surge in academic output related to the topic of technology, reflecting a growing interest in understanding the interaction between technological factors and consumer behavior. The study also explores trends in international collaboration in publications as well as its impact on citation counts.

The Schwarzschild metric emerges independent of Einstein's field equations, offering a straightforward derivation solely reliant on Newtonian mechanics and Minkowskian proper acceleration. This approach provides a clear path to understanding the gravitational field around a spherically symmetric mass without the need for the complexities of Einstein's full theory of General Relativity. Transitioning to our exploration of the cosmic Friedmann equations, we adopt a novel perspective rooted in a Lagrangian formulation grounded in Newtonian mechanics and the first law of thermodynamics. Our investigation operates under the assumption that the universe is populated by either a perfect fluid or a scalar field. By elucidating the intricate interplay between the Lagrangian formulation and the cosmic Friedmann equations, we uncover the fundamental principles governing the universe's dynamics within the framework of these elemental constituents. In our concluding endeavor, we embark on the task of harmonizing the classical equations—namely, the conservation, Euler, and Poisson equations—with the principles of General Relativity. This undertaking seeks to extend these foundational equations to encompass the gravitational effects delineated by General Relativity, thus providing a comprehensive framework for understanding the behavior of matter and spacetime in the cosmic context.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

Introduction: It has long been accepted that trauma is one of the most important and frequent predisposing factors for onychomycoses . However, the role of direct trauma in the pathogenesis of fungal nail infections was only recently been elucidated in a series of 32 cases of post-traumatic single-digit onychomycosis. The importance of repeated trauma due to foot and toe abnormalities was rarely investigated.Aim of the study: This is a multicenter single-author observational study over a period of 6 years performed at a specialized nail clinic in three countries. All patient photographs taken by the author during this period were screened for toenail alterations and all toe onychomycosis cases were checked whether they contained enough information to evaluate potential foot and toe abnormalities. Particular attention was paid to the presence of hallux valgus, hallux valgus interphalangeus, hallux erectus, inward rotation of the big toe and outward rotation of the little toe, as well as splay foot. Only cases with unequivocal proof of fungal nail infection by either histopathology, mycologic culture or polymerase chain reaction (PCR) were accepted.Results: Of 1653 cases, 185 were onychomycoses proven by mycologic culture, PCR or histopathology. Of these, 179 involved at least one big toenail, 6 affected one or more lesser toenails. Three patients consulted us for another toenail disease and the onychomycosis was diagnosed as a second disease. Eight patients had a pronounced tinea pedum. Relatively few patients had a normal big toe position (n = 9). Most of the cases had a mild to marked hallux valgus (HV) (105) and a hallux valgus interphalangeus (HVI) (143), hallux erectus was observed in 43 patients, the combination of HV and HVI was observed 83 times. Discussion: The very high percentage of foot and toe deformations was surprising. It may be hypothesized that this is not only a pathogenetically important factor but may also play an important role for the localization of the fungal infection as no marked hallux deviation was noted in onychomycoses that affected the lesser toes only. As the management of onychomycoses is a complex procedure involving the exact diagnosis with determination of the pathogenic fungus, the nail growth rate, the type of onychomycosis, its duration and predisposing factors, anomalies of the toe position may be important. Among the most commonly mentioned predisposing factors are peripheral circulatory insufficiency, venous stasis, peripheral neuropathy, immune deficiency and iatrogenic immunosuppression whereas foot problems are not given enough attention. Unfortunately, many of these predisposing and aggravating factors are difficult to treat or to correct. Generally, when explaining the treatment of onychomycoses to the patients, the importance of these orthopedic alterations is not or only insufficiently discussed. In view of the problems encountered with the treatment of toenail mycoses, this attitude should be changed in order to make the patient understand why there is such a low cure rate despite excellent minimal inhibitory drug concentrations in the laboratory.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers is impaired due to the stratum corneum layer, which acts as barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consists on an array of microscale needles. This particular biomedical device had been drawing attention due to their ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size and composition. The design process of a microneedle device must take in account several factors, like the location delivery, the material and manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application, cosmetics, therapy, diagnosis, tissue engineering, sample extraction, cancer research, wound healing, among others.

This article investigates the fundamental principles that establish universal limits in physical phenomena, such as the uniformity of physical laws and Energy conservation, leading to the concepts of maximum speed, locality, and maximum density. These principles guide me to explore Quantum Black Holes—relativistically rotating, miniature charged black holes with a singular core at the highest possible density. Uniquely, these Quantum Black Holes maintain all quantized charges, including gravitational ones. The study further demonstrates that quarks and leptons are composed of these Quantum Black Holes, redefining them as the actual elementary particles.Exploring these particles reveals that they emit Energy outward, modifying the curvature of nearby space-time. This discovery provides new insights into local space-time dynamics, characterized by a single equation that includes the influence of all charges and hidden Energy. By the conclusion of this article, I show that Quantum Black Holes offer explanations for several Standard Model deficiencies: the nature of luminous, dark, and anti-Matter; the mass, size, and quantized charges of all elementary particles (including gravitational); the nature of neutrino oscillations; and the mechanism by which electric charges remain bound even though the same type of electric charge components must repeal each other.

It is proved that there exist two odd prime numbers, p_i and p_j , such that p_i + p_j = 2r + 2(r ⩾ 2), where p_n denote the n-th odd prime number, 1 ⩽ i, j ⩽ n. By the theory of generating functions, we prove that there exist two positive integers, h_i and h_j , such that h_i + h_j = r(r ⩾ 2), where h_n = (p_n − 1)/2，(p_n ⩾ 3).Then we complete the proof.

Industry 4.0 is an industrial paradigm that is causing changes in form and substance in factories, companies and businesses around the world, and is impacting work and education in general. In fact, the disruptive technologies that frame the fourth industrial revolution have the potential to improve and optimize manufacturing processes and the entire value chain, which can lead to an exponential evolution in the production and distribution of goods and services. All these changes imply that the fields of engineering knowledge must be oriented towards the concept of Industry 4.0, for example Mechanical Engineering. The development of various physical assets that are used by cyber-physical systems and digital twins is based on Mechanics. However, the specialized literature on Industry 4.0 says little about the importance of Mechanics in the new industrial era and more importance is given to the evolution of Information and Communication Technologies and Artificial Intelligence. This article presents a frame of reference about the importance of Mechanical Engineering in Industry 4.0 and proposes an extension to the concept of Mechanics 4.0, recently defined as the relationship between Mechanics and Artificial Intelligence. For the analysis of Mechanical Engineering in Industry 4.0, the criteria of the four driving forces that defined Mechanics in the third industrial revolution was used. An analysis of Mechanical Engineering Education in Industry 4.0 is presented, and the concept of Mechanical Engineering 4.0 Education is improved. Finally, the importance of making changes in the educational models of engineering education is described.

The draconian regulation required by the inherent instability of cognitive phenomena -- gene expression, immune function, cancer suppression, wound healing, animal consciousness, machine intelligence, network stabilization, institutional cognition, and their many and varied composites -- can be viewed through the lens of the asymptotic limit theorems of both information and control theories. Here, we explore the dynamics and sometimes highly punctuated failures of the regulation of cognition under increasing `noise'. The approach parallels, and indeed generalizes, the Data Rate Theorem of control theory, extending the theorem's requirement of a minimum channel capacity necessary for stabilization of an inherently unstable system. Various models are explored across different basic underlying probability distributions characteristic of the system under study, and across different hierarchical scales, finding the addition of adaptive -- learned -- regulation greatly extends the reach of innate -- e.g., AI-driven or otherwise pre-programmed -- regulation. This work points toward the construction of new statistical tools for the analysis of observational and empirical data across a wide spectrum of inherent pathologies and adversarial challenges afflicting a wide variety of cognitive processes.

In this paper we present two ways to solve the Jacobian conjecture. The first way is an equivalent statement to the Jacobian conjecture using idempotent ideals. The second way is to use an equivalent thesis to the thesis of the Jacobian conjecture. In both cases we will show that the Jacobian conjecture is true.

The present article seeks to study whether there is any relationship between the equation of the rhythmic figures (Lugos Abarca, 2023) and cardiac auscultation using Field's method, which consists of representing cardiac sounds by means of musical notation (Field, 2010). A new meaning is given to the equation, concluding a mathematical equality between the equation of the rhythmic figures and the formula for calculating the RR Interval.