Astrocytes, the most abundant glial cells in the brain, are an integral part of the synaptic compartment and contribute to synaptic pruning, a key process for refining neural circuits during early postnatal development (PND). Dysregulations in this process are implicated in various neuropsychiatric disorders, including major depressive disorder (MDD). To investigate astrocyte functions in a physiologically relevant context, organotypic brain slice cultures (OBSCs) offer a powerful model, reproducing more closely in vivo conditions than traditional cell cultures and preserving complex brain architecture and interactions. Here, we present OBSCs as an ex vivo culturing method to provide a platform to explore astrocyte-mediated synaptic pruning dynamics in the rat prefrontal cortex (PFC) during PND. Our approach is based on assessing the role of MEGF10, a key protein involved in synaptic pruning, alongside the synaptic markers synaptophysin and PSD95, using Western blotting to analyse the expression levels of these markers in the cortex of developing rat pups. Additionally, we combine immunofluorescence staining with confocal imaging and IMARIS 9.8 software-assisted analysis to investigate the co-localization of the lysosomal marker LAMP1 with synaptic and astrocytic markers to evaluate the precise rate of synaptic engulfment. The methods presented here allow a deeper examination of an astrocyte-mediated synaptic remodelling in healthy and pathophysiological conditions.

Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an Organotypic Brain Slice Culture (OBSC) system.Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D-analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodelling during PND and might be exploited to investigate pathomechanisms of brain disorders with aberrant synaptic development.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

This study presents the first genome assembly of the freshwater saprobe fungus Neonectria lugdunensis and a comprehensive phylogenomics analysis of the Nectriaceae family, examining genomic traits according to fungal lifestyles. The Nectriaceae family, one of the largest in Hypocreales, includes fungi with significant ecological roles and economic importance as plant pathogens, endophytes, and saprobes. The phylogenomics analysis identified 2684 single-copy orthologs, providing a robust evolutionary framework for the Nectriaceae family. We analyzed the genomic characteristics of 17 Nectriaceae genomes, focusing on their carbohydrate-active enzymes (CAZymes), biosynthetic gene clusters (BGCs), and adaptations to environmental temperatures. Our results highlight the adaptation mechanisms of N. lugdunensis, emphasizing its capabilities for plant-litter degradation and enzyme activity in varying temperatures. Comparative genomics of different Nectriaceae lifestyles revealed significant differences in genome size, gene content, repetitive elements, and secondary metabolite production. Endophytes exhibited larger genomes, more effector proteins, and BGCs, while plant pathogens had higher thermo-adapted protein counts, suggesting greater resilience to global warming. In contrast, the freshwater saprobe shows less adaptation to warmer temperatures and is important for conservation goals. This study underscores the importance of understanding fungal genomic adaptations to predict ecosystem impacts and conservation targets in the face of climate change.

This study examines change detection techniques in dense point clouds for the purpose of Cultural Heritage preservation, with a particular focus on the San Pietro Barisano Bell Tower in Matera, Italy. Dense point clouds, obtained via advanced laser scanning, offer detailed 3D representations of heritage structures, facilitating the precise monitoring changes over time. The investigation uses a variety of change detection algorithms, including the Iterative Closest Point (ICP) algorithm, which is renowned for its robust registration capabilities in aligning point clouds with high accuracy. The combination of ICP with deviation analysis and feature-based methods allows for the effective identification of alterations, including deformations, material loss, and surface degradation. This methodology establishes a comprehensive framework for the monitoring of Cultural Heritage, thereby enabling timely and targeted preservation efforts. The results emphasise the substantial contribution of dense point cloud analysis to the enhancement of heritage management and the safeguarding of vulnerable architectural sites.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

A central hypothesis on brain functioning is that plasticity regulates the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granular layer has been shown to control the gain of signals transmitted through the mossy fiber pathway. Until now, the impact of plasticity on incoming activity patterns was analyzed by combining electrophysiological recordings in acute cerebellar slices and computational modeling, unraveling a broad spectrum of different forms of synaptic plasticity in the granular layer, often along with forms of intrinsic excitability changes. Here, we attempt to provide a brief overview of the most prominent forms of plasticity at excitatory synapses formed by mossy fibers onto principal neurons (granule cells, Golgi cells and unipolar brush cells) in the granular layer. Specifically, we will highlight current understanding of the mechanisms and their functional implications of the synaptic and intrinsic plasticity, providing valuable insights into how inputs are processed and reconfigured at the cerebellar input stage.

Short video addiction refers to a psychological dependency on short video applications, characterized by an intense attachment and an inability to control usage, leading to typical addiction symptoms. While its definition bears similarities to substance addiction, significant differences also exist. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), published in 2013, short video addiction has not yet been officially classified as an addiction disorder. To facilitate more in-depth and standardized research on short video addiction, it is essential to synthesize and organize existing studies on its theoretical foundations and mechanisms.

The AUC-ROC is a widespread measure to assess the performance of a binary classification model across various discrimination thresholds. Yet, it is not apt for unbalanced class problems and is misleading for early retrieval. For instance, link prediction in complex networks is an unbalanced early retrieval problem, whose goal is to offer a ranking of the nonobserved network links, prioritizing a small cohort of positive links (for which we are sure the labels are reliable) on top of a list largely populated by unlabeled links (for which the labels are uncertain). Differently from binary classification, here the evaluation focuses on how the predictor prioritizes the positive class, because the negative class does not exist and is replaced by an unlabeled class. For decades, scholars have been investigating the necessity to correct and to generalize the AUC-ROC to work for both unbalanced classification and early retrieval evaluation, this is requested in many applied domains of computational science. Here we propose the area under the magnified ROC (AUC-mROC), a new measure that adjusts the standard AUC-ROC to work for unbalanced early retrieval problems such as link prediction. Finally, we introduce the area under the generalized ROC (AUC-gROC), which unifies both AUC-mROC and AUC-ROC to provide a universal and reliable evaluation measure that can work for both classification and early retrieval problems, regardless of class proportion.This discovery represents a critical achievement, culminating in success after decades of contentious research. Its solution promises to significantly impact various domains within applied computational science.

Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. Postmortem confirmation of rabies traditionally involves invasive brain tissue testing, a process met with resistance from deceased patients' families, impeding consent. This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. This method preserves the cadaver's integrity, potentially easing family reluctance towards autopsies. The limited testing of both human and animal rabies in Ghana highlights the challenges in diagnosing this fatal disease. Scarce diagnostic resources and the complexity of obtaining brain tissue samples exacerbate the issue. Cultural and religious beliefs surrounding autopsies contribute to familial hesitation, viewing these procedures as disruptive and disfiguring, further complicating consent. The transnasal technique involves approaching the brain tissue through the nostrils and cribriform plate without any superficial manipulation of the patient's head and face, thereby preserving aesthetics and natural features of the person. Technological advancements and seamless One Health collaboration among governmental, non-governmental, and research entities locally and globally culminated in Ghana's first confirmed rabies diagnosis using this method of brain tissue collection. This success emphasizes the efficiency and feasibility of transnasal brain collection approach and the invaluable role of the One Health approach and collaborative efforts in overcoming diagnostic challenges in rabies control.

Chip pad alignment inspection is of great importance in the industrial field. However, due to the fact that chip pads are usually small, problems such as misdetection and missed detection often occur. When applying deep learning methods for chip pad detection, it is necessary to ensure accurate detection of small target chips while meeting the requirements of lightweight detection models for industrial needs. To solve the above problems, this paper proposes a lightweight model based on improved YOLOv5s. Firstly, the feature extraction part is improved to increase the network's focus on the target. Secondly, the feature fusion layer is improved to double the resolution of the prediction head, and the context-aware network is designed to enhance the context-capture ability of key features of small targets. Finally, SIoU is adopted as the loss function to improve the speed and accuracy of the regression frame. The experimental results show that the improved YOLOv5s algorithm improves the detection accuracy by 2.3% and reduces the network parameters by 81.8% compared to the original algorithm. The improved algorithm is combined with image processing techniques to design correction methods for alignment anomalies and realize real-time alignment anomaly correction in industry.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

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

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

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Bixonimania, a rare hyperpigmentation disorder characterized by a distinctive pink hue on the eyelids, presents a significant diagnostic challenge due to its unique presentation and limited research. This study explores the application of machine learning algorithms for bixonimania detection by analyzing millions of images of individuals exposed to blue light (500-700 nm spectrum). Our findings suggest a potential link between blue light exposure and bixonimania, affecting roughly 1 in 90,000 individuals. The proposed machine learning model achieved an accuracy of 92% in detecting bixonimania based on eyelid hue analysis. This study paves the way for further exploration of bixonimania's underlying causes, improved diagnostic tools, and potential treatment options.

Background: many studies, on for example taste-visual dissonance, have shown that the influence of the visual cortex on taste sensation is enormous. The aim of the presented work is to investigate, using fNIRS, whether a taste stimulus, in this case the taste of bitter, also causes stimulation of the visual cortex in fNIR study. Methods: 51 participants (204 examinations, 9 996 records) were examined with fNIRS, which collects signals from whole left hemisphere. Differences between the maximum and minimum changes in oxyHb concentrations (ΔoxyHb) for the areas of the brain cortex considered responsible for recording visual and gustatory signals were analyzed. Protocol I, II, III and IV – activation with distillate water, coffee with lower concentration, reference (no stimulation) and coffee with higher concentration respectively, were used. Results: We recorded high signals for teste activation on channels covered gustatory cortex, which confirms the correctness of the choice of research method. What seems important, and somewhat surprising, is the fact that we also received high signals for the channels 45-49, which cover the visual cortex. The statistical analysis does not show any statistical differences between the protocols I, II and IV (different taste activation – water, coffee A and coffee B) for specific channels. As a results of the analysis of the correlation between the subjective bitterness assessment solutions, and the signal ΔoxyHb height, it was observed that statically important correlation, although weak, occurs only for 14 and gustatory channels, only for coffee with a higher concentration. Additionally we recorded the only statistically significant difference between women and men for protocol I (water), where the ΔoxyHb signal was twice as high for women. Conclusions: In conclusion, we can clearly state that the senses of sight and taste work closely together. Moreover, this cooperation is not one-sided - not only the visual activation affects the perception of taste, but interestingly, the taste stimulus can generate a hemodynamic response - activity in the visual cortex.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

Sparse training (ST) aims to ameliorate deep learning by replacing fully connected artificial neural networks (ANNs) with sparse or ultra-sparse ones, such as brain networks are, therefore it might benefit to borrow brain-inspired learning paradigms from complex network intelligence theory. Here, we launch the ultra-sparse advantage challenge, whose goal is to offer evidence on the extent to which ultra-sparse (around 1% connection retained) topologies can achieve any leaning advantage against fully connected. Epitopological learning is a field of network science and complex network intelligence that studies how to implement learning on complex networks by changing the shape of their connectivity structure (epitopological plasticity). One way to implement Epitopological (epi- means new) Learning is via link prediction: predicting the likelihood of non-observed links to appear in the network. Cannistraci-Hebb learning theory inspired the CH3-L3 network automata rule for link prediction which is effective for general-purpose link prediction. Here, starting from CH3-L3 we propose Epitopological Sparse Meta-deep Learning (ESML) to apply Epitopological Learning to sparse training. In empirical experiments, we find that ESML learns ANNs with ultra-sparse hyperbolic (epi-)topology in which emerges a community layer organization that is meta-deep (meaning that each layer also has an internal depth due to power-law node hierarchy). Furthermore, we discover that ESML can in many cases automatically sparse the neurons during training (arriving even to 30% neurons left in hidden layers), this process of node dynamic removal is called percolation. Starting from this network science evidence, we design Cannistraci-Hebb training (CHT), a 4-step training methodology that puts ESML at its heart. We conduct experiments on 7 datasets and 5 network structures comparing CHT to dynamic sparse training SOTA algorithms and the fully connected counterparts. The results indicate that, with a mere 1% of links retained during training, CHT surpasses fully connected networks on VGG16, GoogLeNet, ResNet50, and ResNet152. This key finding is an evidence for ultra-sparse advantage and signs a milestone in deep learning. CHT acts akin to a gradient-free oracle that adopts CH3-L3-based epitopological learning to guide the placement of new links in the ultra-sparse network topology to facilitate sparse-weight gradient learning, and this in turn reduces the convergence time of ultra-sparse training. Finally, CHT offers the first examples of parsimony dynamic sparse training because, in many datasets, it can retain network performance by percolating and significantly reducing the node network size. Our code is available at: https://github.com/biomedical-cybernetics/Cannistraci-Hebb-training.

(1) Exoskeletons offer potential benefits for overhead working tasks, but gender effects or differences are unclear. This study aimed to compare the performance, strain, and comfort of men and women using an upper-body exoskeleton. (2) n=20 female and n=16 male participants performed an overhead drilling task with and without a passive upper-body exoskeleton in a randomized cross-over study. Task performance of different movement phases, perceived exertion, and ease of use were measured to compare gender differences. One and two-way analyses were used to com-pare genders in the different conditions. (3) Gender differences after controlling for BMI in task performance were found for error integrals (p <.001) with higher values in male participants. Moreover, there was a significant interaction effect for gender x exoskeleton use. While females showed performance decrements in aiming with exoskeleton use, the male's performance increased (p=.025). No other gender differences were observed. (4) Gender differences in task performance using an upper-body industrial exoskeleton were less detectable than expected after controlling for BMI, indicating that body composition and anthropometrics might be valuable indicators for per-formance including assisting devices. Moreover, future studies should also integrate the examina-tion of muscle activity to gain more insights into potential gender movement control patterns.

Dynamic sparse training is an effective strategy to alleviate the training and inference demands of artificial neural networks. However, current sparse training methods face a challenge in achieving high levels of sparsity while maintaining performance comparable to that of their fully connected counterparts. The Cannistraci-Hebb training (CHT) method produces an ultra-sparse advantage compared to fully connected training in various tasks by using a gradient-free link regrowth method, which relies solely on the network topology. However, its rigid selection based on link prediction scores may lead to epitopological local minima, especially at the beginning of the training process when the network topology might be noisy and unreliable. In this article, we introduce the Cannistraci-Hebb training soft rule (CHTs), which applies a flexible approach to both the removal and regrowth of links during training, fostering a balance between exploring and exploiting network topology. Additionally, we investigate the network topology initialization using several approaches, including the bipartite scale-free and bipartite small-world network models. Empirical results show that CHTs can surpass the performance of fully connected networks with MLP architecture by using only 1% of the connections (99% sparsity) on the MNIST, EMNIST, and Fashion MNIST datasets and can provide remarkable results with only 0.1% of the links (99.9% sparsity). In some MLPs for image classification tasks, CHTs can reduce the active neuron network size to 20% of the original nodes (neurons), demonstrating a remarkable ability to generalize better than fully connected architectures, reducing the entire model size. This represents a relevant result for dynamic sparse training. Finally, we present evidence from larger network models such as Transformers, with 10% of the connections (90% sparsity), where CHTs outperform other prevalent dynamic sparse training methods in machine translation tasks.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Major depressive disorder (MDD) is a prevalent mental health condition with substantial social and economic consequences. This study focuses on the interplay between genetic and environmen-tal factors in MDD, with particular emphasis on epigenetic mechanisms such as stochastic epige-netic mutations (SEMs), epigenetic age acceleration, and epigenetic drift. We conducted a meta-analysis of DNA methylation patterns across six datasets (n=1125 MDD cases, 398 controls in whole blood; n=95 MDD cases, 96 controls in brain tissues) from the Gene Expression Omnibus. The analysis did not reveal significant global methylation differences between MDD cases and controls. However, a brain-specific probe (cg25801113) near the SHF gene consistently exhibited hypomethylation, suggesting its potential relevance to MDD. SEMs were assessed, revealing a dis-tinct burden at the gene level in MDD cases, though no significant findings emerged for epigenetic age acceleration, indicating it may not play a central role in MDD. The study also identified rare epivariations in specific genes unique to MDD cases. In blood tissue, 51 genes were associated with these unique epivariations, while 1 gene was highlighted in the brain tissue. These results un-derscore the importance of exploring rare epivariations in understanding the molecular mecha-nisms underlying MDD and offer potential targets for further investigation.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

This study explores innovative strategies to enhance hands-on learning experiences in a Database Management Systems (DBMS) course while addressing challenges related to software installation complexities and financial barriers. The investigation focuses on an online course format catering to students majoring in information systems, healthcare administration, business administration, and marketing. Traditional software installation hurdles, especially for complex systems like Microsoft Access and MySQL, can impede students' engagement and access. To overcome these challenges, the study proposes leveraging cloud-based solutions and clientless remote desktop gateways like Apache Guacamole. Results indicate that these approaches effectively eliminate software installation obstacles, ensuring seamless access to essential tools for all students. The study underscores the importance of innovative technological solutions in promoting inclusive and impactful learning environments in higher education.

The representation of intelligence is achieved by patterns of connections among neurons in brains and machines. Brains grow continuously, such that their patterns of connections develop through activity-dependent specification with the continuing ontogenesis of individual experience. The theory of active inference proposes that the developmental organization of sentient systems reflects general processes of informatic self-evidencing, through the minimization of free energy, that may be described in information terms that are not dependent on a specific physical substrate. At a certain level of complexity, self-evidencing of living (self-organizing) information systems becomes hierarchic and reentrant, such that effective consciousness emerges as the consequence of a good regulator. These principles imply that an adequate reconstruction of the computational dynamics of an individual human brain is possible with a sufficient neuromorphic emulation.

The landscape of business intelligence (BI) is marked by rapid growth, extensive research, and practical implementations, reflecting its sustained relevance in modern business strategies. This paper delves into the dynamics of BI, particularly focusing on the interplay between maturity and agility. While BI maturity emphasizes optimization and predefined goals, BI agility prioritizes adaptability and response to change. The paper highlights the contradictions between these concepts, emphasizing the need for a balanced approach in BI strategy formulation.The role of organizational culture in fostering BI agility is explored through literature review and interviews with BI professionals. Key insights include the necessity of an open culture for effective BI utilization, clear strategic vision, decision delegation, information sharing, business-IT cooperation, and a learning-oriented mindset. These cultural factors contribute significantly to BI effectiveness and the ability to navigate dynamic business landscapes. The paper proposes pillars of agile maturity supported by an open organizational culture, including efficient communication, information integration, creative problem-solving, and close collaboration between business and IT. These pillars underscore the importance of a flexible and open mindset in navigating BI challenges and ensuring sustained value. Empirical validation and further research are suggested to deepen our understanding of the impact of organizational culture on BI agility and effectiveness.

Studies of mast cell biology is dependent on relevant and validated in vitro models. We here present detailed information concerning the phenotype of both freshly isolated human skin mast cells (MCs), and of in vitro cultures of these cells that was obtained by analyzing their total transcriptome. Transcript levels of MC-related granule proteins and transcription factors were found to be remarkably stable over a 3-week culture period. Relatively modest changes were also seen for important cell surface receptors including the high affinity receptor for IgE, FCER1A, the low affinity receptor for IgG, FCGR2A, and the receptor for stem cell factor, KIT. FCGR2A was the only Fc receptor for IgG expressed by these cells. Comparisons of the present transcriptome against previously reported transcriptomes of mouse peritoneal MCs and mouse bone marrow derived MCs (BMMCs) revealed both similarities and major differences. Strikingly, cathepsin G was the most highly expressed granule protease in human skin MCs, in contrast to the almost total absent of this protease in both mouse MCs. Transcript levels for the majority of cell surface receptors were also very low compared to the granule proteases in both mouse and human MCs, with a difference of almost two orders of magnitude. An almost total absence of T cell granzymes was observed in human skin MCs, indicating that granzymes have no or only a minor role in human MC biology. Ex vivo skin MCs expressed high levels of selective immediate early genes and transcripts of heat-shock proteins. In validation experiments, we determined that this expression was an inherent property of the cells and not the result of the isolation process. Three to four weeks in culture results in an induction of cell growth related genes accompanying their expansion by 6-10-fold, which increases the number of cells for in vitro experiments. Collectively, we show that cultured human skin MCs resemble their ex vivo equivalents in many respects and are a more relevant in vitro model compared to mouse BMMCs for studies of MC biology, in particular human MC biology.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Accumulating psychedelic research has demonstrated potential for improving mental health and wellbeing, yet studies in the context of eating disorders (EDs) are limited. This study explores the subjective effects of psychedelic experiences to gain insight into the benefits and risks for people with EDs. Semi-structured interviews were conducted with 11 eligible adults. A purposive sample of eight adults aged 25-54 (M =  36.9) with chronic EDs, diagnosed (N = 7) and undiagnosed (N = 1) were thematically analysed. Reports of cessation or reduction of ED symptoms were unanimous, with two participants reporting recovery, attributed to psychedelic use. Thematic analysis resulted in two superordinate themes, each comprising three subordinate themes. The first superordinate theme, ‘Exploring’ via the ‘gateway to healing’, illustrates mental, emotional, and transcendental elements of psychedelic experiences. The second superordinate theme, ‘Transformation’ and being ‘able to do the work’, illustrates cognitive and behavioural outcomes, with retrospective safety perceptions. This research presents an account representative of the ED population for the therapeutic potential for psychedelic experiences to reduce symptoms and improve wellbeing. Findings provide evidence of therapeutic feasibility to support larger scale research, emphasising the therapeutic use of psychedelics as a potentially promising avenue for chronic and treatment resistant EDs.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

Sensory integration is an essential function of human life, and its decline causes difficulties in the quality of life, especially in older adults. In this study, we proposed an arm-reaching task based on a virtual reality head-mounted display (VR-HMD) system to assess sensory integration in daily life, and examined whether reaching task performance was associated with age and resting-state functional connectivity (rsFC) between the brain regions of interest involved in sensory integration. We hypothesized that performance during a reaching task with multiple cognitive loadings would be affected by aging. The gap angle between the reaching hand and target positions was compared between older and middle-aged adults as a measure of sensory integration function. In addition, rsFC, which was significantly correlated with the gap angles of individual participants in the older adult group, was identified using resting-state functional magnetic resonance imaging data. The mean gap angle was significantly larger in the older adults than in the middle-aged group and was also significantly correlated with connections between the left primary motor area and the left inferior temporal gyrus, temporo-occipital part. Because the connectivity between the areas is known to be related to visuomotor integration, the results suggest the involvement of visuomotor integration in the decline of sensory integration function in old age and the validity of the gap angle during the proposed VR-HMD task as an index for the decline in function.

This study investigated interactions between sugar-related dietary patterns (DP), personality traits, cognitive-behavioural, and emotional functioning. The study involved females aged 18-54. Data were collected between the Winter and Spring of 2020/21. The survey was conducted using anonymized questionnaires. The Ten-Item Personality Inventory (TIPI) was used to examine personality traits based on the Big Five Personality Trait Model. Three-Factor Eating Questionnaire (TFEQ) was used to measure eating behaviours: cogni-tive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The KomPAN question-naire collected the frequency of intake. Dietary patterns (DPs) were derived by principal component analysis (PCA). A logistic regression (OR) was applied to verify the association between the DPs, personality traits, cognitive-behavioural and emotional functioning. Three DPs were identified: sweet-western (SWDP), pro-healthy (PHDP) and dairy (DDP). Women with high conscientiousness were less likely, by 33%, to adhere to the upper tercile of SWDP and 80% more likely to the upper tercile of PHDP. Elevated CR intensity increased by almost 2-fold (OR: 1.93; p

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

REV-ERBα and its paralog, REV-ERBβ encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock that can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes were controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provided strong evidence for isoform-dependent actions. For example, REV-ERBα were more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components required REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways, despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators may help treat metabolic disturbances and certain types of cancer.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

Ramsey’s theory (RAM) from combinatorics and network theory goes looking for regularities and repeated patterns inside structures equipped with nodes and edges. RAM represents the outcome of a dual methodological commitment: by one side a top-down approach evaluates the possible arrangement of specific subgraphs when the number of graph’s vertices is already known, by another side a bottom-up approach calculates the possible number of graph’s vertices when the arrangement of specific subgraphs is already known. Since natural neural networks are often represented in terms of graphs, we suggest to utilize RAM for the analytical and computational assessment of a peculiar structure supplied with neuronal vertices and axonal edges, i.e., the human brain connectome. We discuss how a RAM approach in neuroscientific issues might be able to locate and trace unexplored motifs shared between different cortical and subcortical subareas. Furthermore, we will describe how notable RAM outcomes, such as the Ramsey’s theorem and the Ramsey’s number, could contribute to uncover still unknown anatomical connexions endowed in neuronal networks and unexpected functional interactions among grey zones of the human brain.

Although being one of the most popular world fibres, wool industry is addressed with severe environmental allegations. While majority of scientific texts does not leave to much doubt about its production negative impact on the ecosystem, wool business does not stop to promote itself via green claims. The internet popular links present a divergent, positive picture of that material, where one might recognize parties being financially involved in such communication. As wool producers or organizations linked to wool business are top positioned in the web as providers of wool green image, the below article brings an interpretation of the industry greenwashing techniques. This comparative analysis of wool umbrella institutions’ webpages exposes myths endorsed about wool’s sustainability. The investigation follows case study of Woolmark brand, where associations to similar, highly ranked websites were conducted likewise. The results have been additionally matched with available scientific data from LCA relative statistics and The Higg Index, to provide contra argumentation from academic sources. The results of this paper could be used both by researchers or fashion lecturers, likewise by fashion marketers to recognize greenwashing techniques, to deliver adequate scientific numbers about unsustainable aspects of wool and to support them in creating a relevant content about wool’s environmental impacts.

With the rapid growth of large language models (LLMs), there is increasing demand for memory and computation in LLMs. Recent efforts on post-training pruning of LLMs aim to reduce the model size and computation requirements, yet the performance is still sub-optimal. In this paper, we present a plug-and-play solution for post-training pruning of LLMs. The proposed solution has two innovative components: 1) Relative Importance and Activations (RIA), a new pruning metric that jointly considers the weight and activations efficiently on LLMs; and 2) Channel Permutation, a new approach to maximally preserve important weights under N:M sparsity. The two proposed components can be readily combined to further enhance the N:M semi-structured pruning of LLMs. Our empirical experiments show that RIA alone can already surpass all existing post-training pruning methods on prevalent LLMs, e.g., LLaMA ranging from 7B to 65B. Furthermore, N:M semi-structured pruning with channel permutation can even outperform the original LLaMA2-70B on zero-shot tasks, together with practical speed-up on specific hardware. Our code is available at: https://github.com/biomedical-cybernetics/Relative-importance-and-activation-pruning

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

This study examines the contribution of early executive functions (EFs) in the association between fluency in reading and arithmetic. Kindergarten children (N = 1,185) were assessed on Executive Functions skills and on reading and arithmetic fluency in Grade 1 and Grade 3. The analysis revealed that beyond the connection within each domain there is a unidirectional effect between fluency measures, with Grade 1 reading fluency significantly influencing the development of arithmetic fluency in Grade 3. Furthermore, the findings indicate that kindergarten EFs significantly contribute to arithmetic fluency at both time points and to reading fluency in the first grade. Early EF skills also emerged as a mediator of associations between fluency performance in reading and arithmetic, suggesting that the influence of EFs extends beyond individual academic domains. These findings have implications for understanding the cognitive mechanisms that underlie the relations between these academic skills.

Staphylococcus aureus is a gram-negative bacterium that causes superficial and deep infections that can be mild or potentially fatal. Recently, the bacterium has gained significant attention due to the increased incidence of multidrug-resistant (MDR) strains that make treatment with antibiotics dif-ficult. Owing to the MDR strains, alternative therapies such as antimicrobial photodynamic therapy (PDT) have emerged as good options to treat non-systemic infections. PDT combines a photosensi-tiser (PS) with light and oxygen to generate free radicals that destroy bacterial structures such as the plasma membrane, matrix, and genetic material. This systematic review aimed to identify the ef-fectiveness of PDT delivered using different types of hydrogels for treating wounds, burns, and contamination by S. aureus. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Bibliographic research was conducted using the PubMed, Web of Science, and Scopus databases. Only full articles published in English between 2013 and 2024 from any country of origin (without restrictions) were included. The research was carried out from 15 June 2023 to 15 June 2024 and did not use any automatic biblio-graphic search tool. The articles collected were identified using keywords and selected using in-clusion and exclusion criteria in accordance with the PRISMA protocol. Seven articles were in-cluded that presented a good set of evidence associated with the use of PDT against S. aureus in in vitro and in vivo studies. To conclude, PDT can effectively complement antimicrobial therapy against S. aureus, in the healing of wounds and burns. The effectiveness of this technique depends on the PS used, hydrogel type, and lesion location. Some studies have already demonstrated the ef-fectiveness of PDT but most were in vitro and a few in vivo. Further studies are required to demonstrate the safety and efficacy of PDT delivered via hydrogels in in vivo models of bacterial infection.

Parental labour migration, either one or both parents, has been associated with various challenges among left-behind children (LBC). However, there is a limited understanding of the LBC’s own views and experiences of social and mental wellbeing and how the new daily life circumstances they encounter following their parents’ migration impact them. This study aimed to understand the influence of parental migration and its aftermath on the social and mental wellbeing of children and adolescents (referred to as LBC) in two rural districts in Indonesia. Employing a qualitative design, data were collected through individual in-depth interviews with LBC (n=24) aged 14 to 18 years, recruited using the snowball sampling technique. Data were thematically analysed, guided by a qualitative data analysis framework. The findings showed that parental migration negatively impacted the social wellbeing of LBC. This impact was reflected in negative labelling from friends and changes in familial roles which influenced their social interactions and activities with peers. Parental migration also caused challenges to the mental wellbeing of LBC. These manifested in the LBC experiencing fractured emotional bonds, leading to negative emotions, including stress, anxiety, sadness, depression, frustration, loss of motivation, and self-imposed isolation, which were associated with their parents’ migration and abrupt disruptions in parent-child communication. The transition to new life situations with caregivers after parental migration and the dynamics within the caregivers’ households were additional factors that detrimentally affected their mental well-being. Unmet basic needs and educational needs due to financial hardships faced by mothers and caregivers, further exacerbated mental health challenges for the children. The findings indicate the importance and improvement of policies and interventions in Indonesia (e.g., counselling services, non-cash food assistance, family hope program, direct cash assistance) that cover and address the diverse needs of mothers or caregivers and the LBC.

The purpose of this study was to establish the association between total and segmental body composition (BC) variables and anaerobic performance and to create optimal models that best predict such performance in CrossFit® (CF) athletes. Fifty athletes, 25 males and 25 females (age: 33.26 ± 6.81 years; body mass: 72.57 ± 12.17 kg; height: 169.55 ± 8.71 cm; BMI: 25.06 ± 2.31 kg·m−2) were recruited to participate and underwent BC analysis using dual-energy X-ray absorptiometry (DXA) and an all-out laboratory test on a cycle ergometer (Wingate) to determine their anaerobic performance. The results show a significant correlation between BC values and performance, ranging from moderate (r = -0.34, p = 0.015) to near-perfect (r = 0.96, p &lt; 0.01). Furthermore, the created performance prediction models exhibited predictive capacities ranging from 19% (p = 0.017) to 93% (p &lt; 0.001). All prediction models were created using total or segmental lean mass variables, excluding others. BC and performance variables found significant differences between males and females. The findings demonstrate that BC variables are crucial indicators of anaerobic performance in CF athletes. Professionals responsible for athlete performance should use this information to monitor athletes and design training programs.

Bats are natural hosts for a wide variety of viruses and could therefore be the reservoir, source and spillover for several mammalian viruses, including adenoviruses. We examined faecal samples from 12 bats (five species of the family Vespertilionidae) from central Russia (Moscow Region) and found that two of them (16%) were positive for mastadenoviruses. One of the identified viruses was isolated from faeces of Nyctalis noctule and named BatAdV/MOW15-Nn19. The genome of the BatAdV/MOW15-Nn19 was 37,915 bp in length. Comparative studies have shown significant divergence of the nucleotide sequence of the BatAdV/MOW15-Nn19 genome from European mastadenoviruses, the highest genome sequence similarity was to isolate WA3301 from an Australian bat. Phylogenetic analysis, as well as a comparative analysis of the protein coding genes to homologous available from public database, showed evidence of novel species within Mastadenovirus genus (preliminary named «K»). Analysis of the short part of the DNA polymerase gene of BatAdV/MOW15-Nn19 reveals few NCBI records from Europe with high identity to the new virus, i.e. mastadenoviruses related to the new species are circulating in European bats. The partial genome of another mastadenovirus from Pipistrellus nathusii was identified, it represented bat adenovirus species B, which is widely distributed in European Vespertilionidae bats. New data on the genetic diversity of bat adenoviruses may help to better understand how they evolved in mammals and spread across Europe.

The load on the top of a slope is an important cause of slope failure, and it is of great significance to study the relationship between the load and the stability of the slope. This paper uses elastic theory and Moore Coulomb's theory as transformation conditions to obtain the slope stability coefficient expression under slope top load based on the Swedish slice method. In view of the actual engineering, the corresponding slope model structure was established, and 5 sliding surfaces were set with the crack on the top of the slope as the shear outlet. According to the slope stability coefficient expression, the stability coefficient of the set sliding surface is solved. The result shows that the slope is unstable under the load. The judgment result is consistent with the GEO-STUDIO check calculation result. This method can provide reference for theory and engineering practice.

State-of-the-art augmented-reality (AR) glasses record their position and orientation in space, enabling measurements and analyses of clinical gait-and-balance tests. This study’s objective was to evaluate concurrent validity and test-retest reliability for common clinical gait-and-balance tests in people with Parkinson’s disease: the Five Times Sit-To-Stand (FTSTS) and Timed Up-and-Go (TUG) tests. Position and orientation data was collected in 22 participants with Parkinson's disease using HoloLens 2 and Magic Leap 2 AR glasses, from which test-completion durations and durations of distinct sub-parts (e.g., sit-to-stand, turning) were derived and compared to reference systems and over test repetitions. Regarding concurrent validity, for both tests an excellent between-systems agreement was found for position and orientation time series and test-completion durations. Between-systems agreement for FTSTS (sub-)durations were all excellent, while TUG turning sub-durations were excellent (turn 1) and moderate (turn 2). Regarding test-retest reliability, the within-system test-retest variation in test-completion times and sub-durations was always much greater than the between-systems variation, implying that these (sub-)durations may be derived interchangeably from AR and reference-system data. In conclusion, AR data are of sufficient quality to evaluate gait and balance in people with Parkinson's disease, with valid quantification of test-completion durations and sub-durations of distinct FTSTS and TUG sub-parts.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Background: This study was designed to adapt the Delis-Kaplan Executive System (D-KEFS) version of the Color-Word Interference (CWIT) and Trail making Tests (TMT) in Greek adult population from 20 to 49 years old, since it is of research as well as clinical importance to detect executive functions’ impairment in young adults with neurological or/and psychiatric conditions. Aims: Norms for the Greek adult population have been calculated to be available for neuropsychologists and health professionals who work in relevant settings. Methods: The study sample consisted of 101 healthy adults (41% male and 60% female), aged 20 to 49 years (M=32.16, SD=11.57) with education from 12 to 19 years of schooling (M=14.51, SD= .89). Pearson correlation test as well as chi square test were conducted to examine potential associations between gender, age, education, and participants’ performance. Afterwards, we calculated normative data using raw scores and transformed them to percentile scores. Finally, Greek norms were compared to the original raw scores, which were transformed in scaled scores by Delis et al. (2001). Results: The findings showed that age was the only variable which affected CWIT, whereas level of education as well as age were predictive factors for most TMT conditions, except for the visual scanning test (Condition 1). Gender did not affect both tests. Finally, D-KEFS norms for CWIT and TMT are available for Greek adult population to help clinicians detect executive functions’ deficits and therefore adjust tailored therapeutic strategies. Additionally, it is of great importance to use these tests for research purposes. Conclusion: Given that executive functions are assumed as high- level skills, which are highly related to everyday functionality, adapted tests contribute not only to assess the progression of any existing neurological as well as psychiatric disorders, but they can also be used to evaluate patients’ ability to live independently, as well as their access to work.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

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.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

Anxiety in older adults is a prevalent yet under-recognized condition associated with significant societal and individual burdens. This study used a machine learning approach to compare the relative importance of 57 risk and protective factors for anxiety symptoms in a population-representative sample of middle-aged and older European adults (N = 65,684; ages 45–103 years; 55.7% women; 15 countries represented). Results revealed loneliness and self-rated poor health as primary risk factors (Nagelkerke R2 = .272), with additional predictive contributions from country of residence, functional limitations, financial distress, and family care burden. Notably, follow-up analysis showed that none of 16 social network variables were associated with loneliness; rather, cohabitating with a partner/spouse was most strongly associated with reduced loneliness. Further research is needed to elucidate directional associations between loneliness and anxiety (both general and sub-types). These findings underscore the imperative of addressing loneliness for mitigating anxiety and related mental health conditions among aging populations.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

Traditional lime-based materials have considerable potential for use as components of green materials for plastering and finishing building surfaces in both new construction and historic heritage conservation. The paper presents the preliminary results of a research activity aimed at developing pre-packaged products based on Traditional Lime Putty (TLP) by partially replacing natural aggregates with Stone Waste Sludge (SWS), with a low rate of recovery from Apricena limestone production district in Apulia. The mineralogical and chemical analysis carried out by means XRD (X-Ray Diffraction), TG-DTA (Thermo Gravimetry-Differential Thermal Analysis) and hydrochloric acid attack test showed that the SWS consisted of 98.4 % CaCO3 by mass. The particle sizes measured by laser diffraction technique are below 22.5 μm for the 92% by mass of the sample. The high fineness of the stone waste was confirmed by the Blaine specific surface method equal to 9273.79 cm2/gr. The behavior of three fresh mixtures for prepacked coarse plaster, fine plaster, and finishing plaster with 12.90%, 17.94%, and 18.90 by mass of SWS, respectively, was evaluated by spreading test and applicability tests on a perforated ceramic slab. The finishing plaster has the highest consistency value of 235 mm, while the fine plaster and the coarse plaster have values of 205 mm and 155 mm, respectively. The coarse plaster is suitable for the use as base plaster (arriccio) or second layer rendering (tonachino) up to a thickness of approximately 1 cm. Both the fine plaster and finishing plasters can be used for the surfaces finishing with the application of layers of a few millimeters thick.

With buildings accounting for a significant portion of global energy consumption and greenhouse gas emissions, the application of artificial intelligence (AI) holds promise for enhancing sustainability in the building lifecycle. This systematic literature review addresses the current understanding of AI's potential to optimize energy efficiency and minimize environmental impact in building design, construction, and operation. A comprehensive literature review and synthesis were conducted to identify AI technologies applicable to sustainable building practices, examine their influence, and analyze the challenges of implementation. The review was guided by a meticulous search strategy utilizing keywords related to AI application in sustainable building design, construction, and operation. The findings reveal AI's capabilities in optimizing energy efficiency through intelligent control systems, enabling predictive maintenance, and aiding design simulation. Advanced machine learning algorithms facilitate data-driven analysis and prediction, while digital twins provide real-time insights for informed decision-making. Furthermore, the review identifies barriers to AI adoption, including cost concerns, data security risks, and challenges in implementation. AI presents a transformative opportunity to enhance sustainability in the built environment, offering innovative solutions for energy optimization and environmentally conscious practices. However, addressing technical and practical challenges will be crucial for the successful integration of AI in sustainable building practices.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2- tuple linguistic model was established. Firstly, based on the establishment of 5 first- grade indicators and 20 second- grade ones, the weight of each indicator is calculated and validated by method of FAHP and root mean square model. Secondly, a path based on the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. Finally, the model is validated by empirical analysis. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the “general” rank. The method including the comprehensive evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

Taking due account of users' perspectives is crucial for improving the quality of healthcare services. This study aimed to analyse the representations and evaluation criteria that users of a public health agency express towards care and treatment services and to explore whether and how the content and meaning of their communications varied according to pre-pandemic, pandemic or post-pandemic periods. 501 communications (73.4% complaints, 16% appreciations, 10.6% enquiries) sent to the public relations office of an Italian health agency were collected. An automatic content analysis procedure (ACASM) was applied to the textual corpus. Four main thematic cores were identified concerning the request for care and respect, the value of the doctor-patient relationship and the difficulties in contacting services and accessing care. Two main latent dimensions of meaning were identified, which capture the dialectic between the demand for relationships and the demand for access to care, and between attention to the relational competence of health workers and attention to the needs and rights of users. Communications collected during the pre-pandemic and post-pandemic periods mainly concern the difficulty of access to care; those collected during the pandemic period mainly concern the doctor-patient relationship. Interpersonal aspects and timely access to care appear to be crucial in users' assessment of the quality of care.

ObjectivesIn increasingly stressful times, many people are increasingly turning to fast food, neglecting to drink enough fluids and often forgoing regular exercise. The fast tempo of everyday life leaves little room for healthy habits, such as cooking at home, which means that a conscious and balanced diet takes a back seat.MethodsA descriptive pilot study was conducted to investigate the effects of an eight-week intervention program. This program included the daily intake of breakfast, cooking at home, adequate fluid intake and daily physical activity. The aim of the study was to evaluate the effects of these measures on the participants' body weight and general health.Results During the 56-day intervention, there was a steady trend towards weight reduction, and at the end of the intervention phase, a significant weight reduction in the test person could be observed. At the end of the intervention, the participant was still 45 years old, measured a body weight of 73.4 kg, which represents a BMI of 25.1 and is classified as slightly overweight. ConclusionThe results of the pilot study demonstrate clearly that the health mix of regular cooking at home, a daily breakfast, a daily physical activity session and sufficient fluid intake can be an effective booster for weight loss in adults. This combination has not only led to a significant reduction in body weight, but has also shown that simple, everyday measures can have a profound effect on health.

Dietary intake of Wistar rats of biofortified with 8-hydroxy-7-iodo-5-quinolinesulfonic acid (8-OH-7-I-5QSA) kale of both cultivars ‘Oldenbor F1’ and ‘Redbor F1’ for 8 weeks resulted in sig-nificantly higher iodine concentrations in the urine and kidneys of rats, which proves iodine bio-availability. Rats diets with 'Oldenbor F1' and 'Redbor F1' kale non- and -biofortified with 8-OH-7-I-5QSA had a significantly lower or a tendency for lower concentration of TSH, triglyc-eride, total and direct bilirubin, TBARs, uric acid, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations in serum. Dietary intake of 'Oldenbor F1' and 'Redbor F1' kale biofortified with 8-OH-7-I-5QSA significantly increased the total antioxidant status (TAS). The study confirms that kale biofortified with iodine in organic form iodoquinoline 8-OH-7-I-5QSA is bioavailable and well absorbed by the Wistar rat and has a positive effect on selected biochemical parameters.

Complexity science studies physical phenomena that cannot be explained by the mere analysis of the single units of a system but requires to account for their interactions. A feature of complexity in connected systems is the emergence of mesoscale patterns in a geometric space, such as groupings in bird flocks. These patterns are formed by groups of points that tend to separate from each other, creating mesoscale structures. When multidimensional data or complex networks are embedded in a geometric space, some mesoscale patterns can appear respectively as clusters or communities, and their geometric separability is a feature according to which the performance of an algorithm for network embedding can be evaluated. Here, we introduce a framework for the definition and measure of the geometric separability (linear and nonlinear) of mesoscale patterns by solving the travelling salesman problem (TSP), and we offer experimental evidence on embedding and visualization of multidimensional data or complex networks, which are generated artificially or are derived from real complex systems. For the first time in literature the TSP’s solution is used to define a criterion of nonlinear separability of points in a geometric space, hence redefining the separability problem in terms of the travelling salesman problem is an innovation which impacts both computer science and complexity theory.

Human longevity is an important but difficult goal due to the extreme complication of human body. If people could repeatedly transfer their consciousness from old bodies to new ones, their lifespan might be prolonged extremely. However, there are several difficulties which prevent the achievement of such a technique. In this paper, we propose an approach that can transfer human consciousness indirectly, and avoid or significantly relieve those difficulties. The strategy of our approach is to integrate the consciousnesses of two bodies (old and new) into a unique consciousness. By doing so, the consciousness is extended to the new body. After that, the consciousness shrinks and remains in the new body when the old body dies. This may also apply to integrating more than two bodies of human, or animal, or even across different species. After investigating thousands of literatures, we find quite strong evidence (related discoveries and technologies) that can support the proposed approach and its advantages. Beside prolonging human lifespan, the approach could also have other meaningful applications.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Thesis Statement: The consumption of externally fermented foods acted as the initial metabolic trigger enabling hominid brain expansion. Because brain tissue is metabolically expensive, it is thought that the evolution of humans’ large brains was only possible through a concomitant reduction in the size of another expensive organ system, the gut. However, this gut reduction must have itself been made possible by dietary changes, the nature of which are still unclear. Here, we propose that the initial metabolic trigger of hominid brain expansion may have been the consumption of externally fermented foods. We define “external fermentation” as occurring outside the body, as opposed to the internal fermentation that occurs through the gut microbiome. This practice could have begun accidentally and with limited understanding, but over time, fermentation technologies may have become increasingly intentional, socially-transmitted, and culturally-reinforced. We detail the mechanisms by which external fermentation can mediate the evolution of increased brain size, as well as a reduction in gut size, by increasing the bioavailability of macro- and micronutrients while reducing digestive energy expenditure. Importantly, we calculate that the reduction in human gut size relative to modern apes is mainly due to a reduction in the colon, the site of internal fermentation. We also discuss the explanatory power of our hypothesis relative to others, including realistic plausibility in hominids with brains roughly the size of modern chimpanzees. Finally, we survey external fermentation practices across human cultures to demonstrate its viability across a huge range of environments, temperatures, and food sources. We close with suggestions for empirical tests.

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% COâ‚‚, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&amp;E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

This research article investigates the application of artificial intelligence (AI) in human resource management (HRM) within the Australian commercial media sector, addressing a critical gap in scholarly knowledge. Despite increasing interest in AI’s potential, there is a lack of consensus among managers and HR professionals regarding its application. Through qualitative interviews with 22 industry professionals, this study examines perceptions, understanding, and the potential for leveraging AI across key HRM functions. Findings indicate significant potential for AI to enhance HRM processes, particularly in job/work design and staffing. This research contributes to a deeper understanding of AI’s role in HRM and offers insights to optimize organizational efficiency and effectiveness in the Australian commercial media sector.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.

Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA and multiplex assay. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

High-intensity interval training (HIIT) is widely used in team sports, particularly in soccer. This study aimed to investigate the effects of a short-term, progressive- load HIIT program on the performance of under-15 soccer players. The sample consisted of 30 adolescent soccer players, aged 14, who were randomly divided into two groups: the control group (CG, n=15) and the intervention group (EX, n=15), which performed additional HIIT sessions. The duration of the training program was six weeks, with progressive overload applied every two weeks. Performance indicators, including speed over 10 and 30 meters, change of direction (COD) to the right and left (505 right and left), maximal oxygen uptake (30-15IFT), and repeated sprint ability (RSA) (RSAtotal, RSAmean, RSAdecrement), were measured before and after the training program. Significant improvement were observed in the intervention group in COD (505 right and left), 30-15IFT, and RSAtotal and RSAmean (p=0.027, p=0.005, p=0, p=0.015, p=0.031, p=0.028, respectively). The findings of the present study suggest that a short-term, progressively overloaded HIIT program can enhance direction change ability, aerobic capacity, and repeated sprint performance.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Multi-step evolution characterizes the carcinogenesis of GI malignancies, where the disease progresses through the accrual of genetic mutations, co-option of multiple host cellular factors and the acquisition of increasingly aggressive pathological features. Ensuing cancer complexity and plasticity are challenges for therapeutic approaches. On the other hand, disease inception is often triggered by a defined oncogenic event, which leads to escalating effects on gene expression, cellular metabolism, chromatin organization and ultimately cell identity. Decoding this molecular cascade of events is crucial to design strategies for early diagnosis as well as to tackle tumor onset. To this aim, the in vitro culture of non-transformed epithelial cells represents a major technical challenge. Genetic studies, combined with lineage-tracing experiments demonstrated that pancreatic cancerous lesions originate from acinar cells, a specialized cell type in the pancreatic epithelium, following mutations of the KRAS oncogene. Ex vivo culture of pancreatic acinar cells has allowed the identification of early mutant KRAS-driven alterations. Primary acinar cells survive in vitro in organoid-like 3D spheroids, which can recapitulate histological and molecular features of disease initiation. Here, we will discuss the isolation and culture of primary mouse pancreatic acinar cells, providing and historical and technical perspective. Impact for pancreatic cancer research will also be debated; in particular we will dissect the role of KRAS signaling in driving oncogenic transformation and highlight differences with canonical 2D culture of established cancer cell lines.

The National Institute of Health Stroke Scale (NIHSS) is used worldwide to classify stroke severity as ‘mild’, ‘moderate’ or ‘severe’ based on neurological impairment. Yet stroke survivors argue that the classification of ‘mild’ does not represent the holistic experience and impact of stroke on their daily lives. In this observational cohort study, we aimed to identify different types of impairment among stroke survivors classified as mild. We used mild stroke survivors’ data from the START longitudinal stroke cohort (n=73) with measures related to sensorimotor, cognition, depression, functional disability, physical activity, work and social adjustment over 12 months. Given the multi-source, multi-granular and unlabelled nature of data, we utilised a structure-adapting, unsupervised machine learning approach, the Growing Self-organising Map (GSOM) algorithm to generate distinct clinical profiles. These diverse impairment profiles revealed that mild stroke survivors experience varying degrees of impairment and impact (cognitive, depression, physical activity, work/social adjustment) at different time points, despite the uniformity implied by their NIHSS-classified ‘mild’ stroke. This emphasises the necessity of creating a holistic and comprehensive representation of mild stroke survivors’ needs over the first-year post-stroke to improve rehabilitation and post-stroke care.

With the exponential growth of internet usage and mobile devices, the volume of user behavior data has surged, offering significant opportunities and challenges for businesses. This paper explores user behavior analysis in the context of big data, highlighting its pivotal role in driving innovation and strategic decision-making. We begin by discussing the importance of user behavior data and reviewing technological advancements such as machine learning, natural language processing, and data mining that enable deep insights into user behavior. Through a case study on linguistic analysis in livestreaming e-commerce, we demonstrate how text-mining techniques can correlate linguistic characteristics with sales performance, providing actionable marketing insights. We further explore the broader business applications, including personalized recommendations, user portraits, product design, and strategic decision-making. Technical and ethical challenges, such as data integration, privacy concerns, and algorithmic bias, are also addressed. The paper concludes with a discussion on future trends, such as AI and ML advancements, edge computing, IoT proliferation, and ethical AI frameworks, poised to shape user behavior analysis. Our findings underscore the transformative potential of user behavior data in enhancing business operations and user experiences, providing recommendations for future research focused on real-time analytics, privacy-preserving techniques, and ethical implications of data-driven decisions.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

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

A joint analysis of solar wind, geomagnetic field, and earthquake catalog data showed that before the catastrophic M7.8 and M7.5 Kahramanmaras earthquake sequence on February 6, 2023, the closed strong magnetic storm occurred on November 7, 2022, SYM/H=-117 nT. Storm started at 08:04 UT. At this time, the high latitudinal part of Turkey's longitudinal region of future epicenters was located under the polar cusp, where the solar wind plasma would directly access the Earth's environment. The time delay between storm onset and earthquake occurrence was ~91 days. We analyzed all seven strong (M7+) earthquakes from 1967 to 2020 to verify the initial findings. A similar pattern has been revealed for all events. The time delay between magnetic storm onset and earthquake occurrence varies from some days to some months. To continue these investigations, a retrospective analysis of seismic and other geophysical parameters just after preceded geomagnetic storms in the epicenter areas is desirable.

Background: Current drug for the treatment of endometriosis is not able of completely cure and significant side effects hinder the continuation of treatment. So, the search for new drug candidates is necessary, and the use of plants extracts is highlighted. Babassu oil and copaiba oilresin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing babassu oil (Orbignya speciosa) (SNEDDS-18) and/or copaiba oilresin (Copaifera langsdorffii) (SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis, and human stromal cells from biopsies of endometriotic lesions (EctESC). Methods: CESC, EuESC and EctESC were established and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate its effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. Results: After 48 hours incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and breakdown the cytoskeleton in EctESCs. After 24h treatment it was observed a decrease in IL-1, TNF-α, and MCP-1, and an increase in IL-10 production. Conclusions: Both nanoemulsions can affect the endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents on the management of endometriosis.

Children are inherently curious about everything they encounter, making the early years a perfect time for STEAM (science, technology, engineering, arts, and math) investigations. An outdoor learning environment can influence STEAM concept formation of preschoolers with intentional design that offer STEAM learning affordances. Despite the rising interest in early STEAM education, there is still limited literature on how the outdoor environment may influence STEAM learning behaviors of preschoolers (3-5 years old). This scoping review intends to evaluate the existing knowledge regarding the physical factors that contribute to STEAM learning affordances in an outdoor environment for children aged 3 to 5. The review included studies from the last twenty years. This scoping review was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). For this scoping review, 843 citations were discovered across four databases (JSTOR, Scopus, EBSCOhost, and Web of Science), ProQuest, and Google Scholar, and 31 articles were considered eligible for inclusion. Through the synthesis of information from those 31 studies, a list of STEAM learning behaviors of children and STEAM activity-supportive settings were identified that may positively influence preschoolers' STEAM concept development.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

This study presents a comprehensive investigation into the spectrum and determinants of child abuse and neglect in Nkpor-Uno, a community in Anambra State, Nigeria. Through a descriptive surveys design, the study explores various forms of abuse and neglect experienced by children, as well as the underlying factors contributing to these phenomena. The population for the study consisted of 1000 parents/ caregivers who are residents of Nkpor-uno. The sample for the study consisted of 100 respondents, purposive sampling techniques was used for the study. The questionnaire was a self-designed structured questionnaire. Data collected were analyzed using frequency, mean and standard deviation. Findings reveal alarming prevalence rates of child maltreatment, including physical, emotional, sexual abuse, and neglect. Socioeconomic factors such as poverty, parental substance abuse, family dynamics, and inadequate sex education emerged as significant contributors to child maltreatment. The study underscores the urgent need for targeted interventions and support systems to address the root causes of abuse and neglect and safeguard the well-being and development of children in Nkpor-Uno. By raising awareness, enhancing access to resources, and promoting positive parenting practices, we can strive towards building a safer and healthier environment for children, ensuring they are protected from harm and given the opportunity to thrive.

A growing number of studies focus on methods to estimate and analyze the functional connectome of the human brain. Graph theoretical measures are commonly employed to interpret and synthesize complex network-related information. While resting state functional MRI (rsfMRI) is often employed in this context, is known to exhibit poor reproducibility, a key factor which is commonly neglected in typical cohort studies using connectomics-related measures as biomarkers. We aimed to fill this gap by analyzing and comparing inter- and intra- subject variability of connectivity matrices as well as graph-theoretical measures in a large (n=1003) database of young healthy subjects which underwent four consecutive rsfMRI sessions. We analyzed both directed (Granger Causality and Transfer Entropy) and undirected (Pearson Correlation and Partial Correlation) time-series association measures and related global and local graph-theoretical measures. While matrix weights exhibit a higher reproducibility in undirected as opposed to directed methods, this difference disappears when looking at global graph metrics and, in turn, exhibits strong regional dependence in local graphs metrics. Our results warrant caution in the interpretation of connectivity studies, and serve as a benchmark for future investigations by providing quantitative estimates for the inter- and intra- subject variabilities in both directed and undirected connectomic measures.

Several studies in recent years have shown that the use of non-Saccharomyces yeasts, used both in single and in mixed fermentations with Saccharomyces cerevisiae can help produce craft beers with distinctive compositional characteristics. The aim of this study was to evaluate the suitability of three Metschnikowia pulcherrima strains, isolated from Albanian vineyards, to be used as starters in the brewing process. Due to its specific enzymatic activities (protease, β-glucosidase and β-lyase) and its low production of hydrogen sulfide, M. pulcherrima 62 was selected as a starter culture for the production of craft beer. Specifically, the aptitude of this yeast to be used in sequential inoculation with S. cerevisiae S04 for the production of an American IPA-style beer and the main volatile compounds produced during fermentation were evaluated. Results showed significant differences in glycerol, isoamyl alcohol and isoamyl acetate content in beer obtained with sequential inoculum of M. pulcherrima 62 with S. cerevisiae S04 compared to beer obtained using S. cerevisiae S04 as a single starter. Therefore, these preliminary data support a candidacy of M. pulcherrima 62 as a new starter in the brewing process.

The number of persons immersed in excessive gaming has increased in this age of rapid digitalization. The World Health Organization and American Psychiatric Association Organization recognizes gaming disorder as a disorder that results in significant problems in daily life as a result of excessive gaming. Both organizations emphasize the similarities to behavioral addictions such as gambling. We examined the appropriate usage of video games from the perspectives of health and management in this study. For the general population, video games provide positive impacts such as stress alleviation and memory improvement. Excessive gaming, on the other hand, might lead to addiction. Gaming addiction is often accompanied by psychological disorders and other addictions, necessitating long-term medical treatment such as cognitive behavioral therapy. Therefore, prevention of gaming disorder is essential. From a societal standpoint, action is required at three levels: the government, game developers, and within the household as a whole. Simultaneously, the public needs to be made understand the positive potential of gaming, such as e-sports.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

Ankle sprains are the most frequently occurring musculoskeletal injuries among recreational athletes. Ankle support through bandages following the initial orthotic treatment might be beneficial for rehabilitation purposes. Since hardly any study has investigated the impact of bandages in the acute phase of ankle sprains, our study examined the immediate effects of wearing an ankle bandage on fine coordination, proprioception, and motor performance in subjects five weeks after an acute ankle injury. In total, 70 subjects with acute unilateral supination trauma were tested. All subjects completed several rating questionnaires and biomechanical investigations, including a fine coordination and proprioception test, single leg stances, the Y-Balance test and gait analysis. All biomechanical investigations were conducted for the subject's injured leg with and without a bandage (MalleoTrain® Bauerfeind AG) and the healthy leg. Subjects reported moderate to strong improvements in ankle stability and pain when wearing the bandage. Wearing the bandage significantly normalized subjects’ single leg stance performance, as well as the stance phase duration, and the vertical ground reaction forces during walking. However, the bandage did not have a clear effect on fine coordination and proprioception. Wearing a bandage in the acute phase of an ankle sprain may immediately improve motor performance, including standing and walking.

The objective of this paper was to verify the applicability of statistical learning (SL) compared to human reasoning with respect to the Universal Thermal Climate Index (UTCI), a complex tool for the assessment of outdoor thermal stress. UTCI is an equivalent temperature index based on the 48-dimensional output of an advanced model of human thermoregulation formed by 12 variables at four consecutive 30-minute intervals, which were calculated for 105642 thermal conditions from extreme cold to extreme heat. Comparing the performance of SL algorithms to the results accomplished by an international endeavor involving more than 40 experts from 23 countries, we found that random forests and k-nearest neighbors closely predicted UTCI values, but that clustering applied after dimension reduction algorithms (principal component analysis and t-distributed stochastic neighbor embedding) were inadequate for risk assessment in relation to the UTCI stress categories. This indicates a potential supportive role for SL, as it will not (yet) fully replace the bio-meteorological expert knowledge.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

Strip steel surface defect recognition research has important research significance in industrial production. Aiming at the problems of defect feature extraction difficulty, slow detection speed and insufficient dataset, YOLOv5 is improved on the basis of YOLOv5, and YOLO-LFPD (Lightweight fine particle detection) model is proposed. By introducing the RepVGG (Re-param VGG) module, the robustness of the model to the surface defect features of strip steel is enhanced, and the expressive ability of the model is improved. FasterNet is used to replace the backbone network, which ensures the accuracy and accelerates the inference speed, making the model more suitable for real-time monitoring. The use of pruning, GA genetic algorithm with OTA loss function method further reduces the model size while better learning the strip steel defect feature information, thus improving the generalisation ability and accuracy of the model. The experimental results show that the introduction of the RepVGG module and the use of FasterNet can well improve the model performance, with a reduction of 48% in the number of parameters, a reduction of 13% in the number of GFLOPs, an inference time of 77% of the original, and an optimal accuracy compared with the network models in recent years. The experimental results on the NEU-DET dataset show that the accuracy of YOLO-LFPD is improved by 3% to 81.2%, which is better than other models, and provides new ideas and references for the lightweight strip steel surface defect detection scenarios and application deployment.