Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

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.

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.

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.

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.

Task fMRI has played a critical role in recognizing the specific functions of the different regions of human brain during various cognitive activities. This study aimed to investigate group analysis and functional connectivity in the Faradarmangars brain during the Faradarmani CF (FCF) connection. Using task functional MRI (task-fMRI), we attempted the identification of different activated and deactivated brain regions during the Consciousness Filed connection. Clusters that showed significant differences in peak intensity between task and rest group were selected as seeds for seed-voxel analysis. Connectivity of group differences in functional connectivity analysis was determined following each activation and deactivation network. In this study, we report the fMRI-based representation of the FCF connection at the human brain level. The group analysis of FCF connection task revealed activation of frontal lobe (BA6/BA10/BA11). Moreover, seed based functional connectivity analysis showed decreased connectivity within activated clusters and posterior Cingulate Gyrus (BA31). Moreover, we observed an increased connectivity within deactivated clusters and frontal lobe (BA11/BA47) during the FCF connection. Activation clusters as well as the increased and decreased connectivity between different regions of the brain during the FCF connection, firstly, validates the significant effect of the FCF and secondly, indicates a distinctive pattern of connection with this non-material and non-energetic field, in the brain.

Background: Patients undergoing brain tumor resection experience changes to their neurocognitive abilities, many of which can be difficult to predict. We hypothesized that changes in brain connectivity could predict changes in neurocognitive functioning, demonstrating the potential for brain connectivity aware surgical planning to provide enhanced outcomes for patients. Methods: Patients underwent functional and diffusion MR scanning and neuropsychological testing before tumor resection and two weeks post-resection. Using this functional and diffusion imaging, we measured changes in the topology of the functional and structural graph networks, respectively. From the neuropsychological testing scores, we derived a composite score that describes a patient’s overall level of neurocognitive functioning. We then used a multiple linear regression model to test if structural and functional connectivity measures could predict changes in composite scores. Results: Twenty-one subjects completed imaging and neuropsychological evaluation both before and after surgery. The multiple linear regression model showed that changes in functional local efficiency were inversely correlated with changes in composite score (p

This article explores the intricate journey of neural progenitor cells from the ventricular zones of the embryonic brain, focusing on their pivotal role in the formation of rich club networks, which are integral to the brain's functional architecture. Initially, the ventricular zones, particularly the cerebral ventricular zone, serve as the primary sites for the proliferation and differentiation of neural progenitors, giving rise to various types of neurons and glial cells. We delve into the sequential migration patterns of these cells, emphasizing how early-migrating neurons, destined to form deeper cortical layers, establish extensive and robust connections, potentially evolving into rich club nodes. These nodes are characterized by their high-degree connectivity and serve as crucial hubs for integrating and disseminating information across disparate brain regions.The article further discusses the implications of this developmental pathway in the context of brain network efficiency, resilience, and cognitive function. We highlight how disruptions in early cell migration can lead to anomalies in rich club formation, drawing connections to various neurodevelopmental disorders such as autism, ADHD and schizophrenia. Additionally, the significance of rich club nodes in maintaining efficient information transfer and network resilience is elucidated, underscoring their role in supporting complex cognitive processes and overall brain dynamics.In summary, this article offers a comprehensive overview of the developmental trajectory from the ventricular zones to the establishment of rich club networks, providing insights into the fundamental processes that shape the brain's intricate connectivity and functional capabilities. Ric

The Internet of Things (IoT) is a concept based on the integration of various devices and methods of communication to exchange information in order to contribute to the improvement of everyday life, business and environment. This paper focuses on the establishment of a modern Internet of Things platform to ensure secure collection, processing and storage of data, under unexpected events. This platform establishes reliable connectivity which enhance system uptime; the key to success when implementing an IoT strategy. For this purpose, we proposed a hybrid approach combining different connectivity technologies to ensure the availability and smooth operation of the system and the prevention of data loss in unforeseen cases.

To investigate the intricate dynamics of brain activity when interacting with a dynamic environment, it is imperative to continuously generate and update expectations regarding forthcoming events and their corresponding sensory and motor responses. This study aims to explore the interconnectivity in time perception across predictable and unpredictable conditions. The necessary data for this study were acquired from EEG signals, sourced from an existing database that involved an experiment conducted on a group of healthy participants. The individuals were subjected to two distinct conditions, predictable and unpredictable, encompassing various time delays. The functional connectivity between brain regions was estimated using a method known as the phase lag index. This method was employed to discern disparities in time perception between the two conditions. A comprehensive comparison of the two conditions across different delays demonstrated noteworthy variations, particularly in the gamma, beta, and theta frequency bands. The differences between delays were more pronounced in the predictable condition. Subsequently, an in-depth analysis was conducted to scrutinize the dissimilarities between the conditions within each delay. Notably, significant differences were observed across all delays. In the unpredictable condition, an increase in connectivity was detected within the alpha band during the 400-ms delay, specifically between occipital and temporal regions. Moreover, the mean connectivity in the unpredictable condition surpassed that of the predictable condition. In the delta band, distinct connectivity patterns were observed across different delays, involving connections between central and frontal regions. Specifically, a heightened connectivity between central and prefrontal regions was noted during the 83-ms delay. Notably, the right hemisphere of the prefrontal cortex played a vital role in time perception. Furthermore, a decline in connectivity across the delta, theta, and beta bands was observed in both conditions during the longest delay (800 ms) when compared to other delays

This study introduces a novel computational approach for testing conditional independence (BB CI test) within causal Directed Acyclic Graphs (DAGs), leveraging Bayesian non-parametric bootstrap and machine learning techniques. Our method offers an alternative for validating the assumptions underpinning causal DAGs. Through simulation studies and an industrial case analysis, we demonstrate the test procedure in accurately assessing conditional independence, comparing it with the Generalized Covariance Measure (GCM) test. Our findings suggest that the BB CI test is advantageous in scenarios where existing methods may falter due to violations of model assumptions. This research contributes to the causal inference literature by providing a computational tool for researchers and practitioners to validate causal models.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

The social- and self-directed behaviours of two golden lion tamarins (Leontopithecus rosalia) was investigated while having residence in the tropical house of Aalborg Zoo, Denmark. The behaviour of the female had been distinct from the male since 2018. Despite several diagnostic examinations and medicinal treatments, the cause of the aberrant and apparently stereotypical behavioural patterns remained undetermined, which initiated this study. The pair were recorded throughout a predetermined observation period and these recordings were analysed to illuminate the behaviours of the individuals. The results showed that there were differences in the type, frequency, and durations of both social- and self-directed behaviours between the sick female and the healthy male. The female expressed both social- and self-directed behaviours more frequently and for longer durations, while the male were more socially reserved and did not engage in social behaviours as frequently. Furthermore, subsequent necropsy of the female revealed uro-genital disease.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

(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.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

Functional connectivity (FC) is a potential candidate that can increase the performance of brain-computer interfaces (BCIs) in the elderly because of its compensatory role in neural circuits. However, it is difficult to decode FC by current machine learning techniques because of a lack of its physiological understanding. To investigate the suitability of FC in BCI for the elderly, we propose the decoding of lower- and higher-order FCs using a convolutional neural network (CNN) in six cognitive-motor tasks. The layer-wise relevance propagation (LRP) method describes how age-related changes in FCs impact BCI applications for the elderly compared to younger adults. Seventeen younger (24.5±2.7 years) and twelve older (72.5±3.2 years) adults were recruited to perform tasks related to hand-force control with or without mental calculation. CNN yielded a six-class classification accuracy of 75.3% in the elderly, exceeding the 70.7% accuracy for the younger adults. In the elderly, the proposed method increases the classification accuracy by 88.3% compared to the filter-bank common spatial pattern (FBCSP). LRP results revealed that both lower- and higher-order FCs were dominantly overactivated in the prefrontal lobe depending on task type. These findings suggest a promising application of multi-order FC with deep learning on BCI systems for the elderly.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

In recent years, advancements in brain science and neuroscience have significantly influenced the field of computer science, particularly in the domain of reinforcement learning (RL). Drawing insights from neurobiology and neuropsychology, researchers have leveraged these findings to develop novel mechanisms for understanding intelligent decision-making processes in the brain. Concurrently, the emergence of quantum computing has opened new frontiers in artificial intelligence, leading to the development of quantum machine learning (QML). This study introduces a novel model that integrates Quantum Spiking Neural Networks (QSNN) and Quantum Long Short-Term Memory (QLSTM) architectures, inspired by the complex workings of the human brain. Specifically designed for reinforcement learning tasks in energy-efficient environments, our approach progresses through two distinct stages mirroring sensory and memory systems. In the initial stage, analogous to the brain’s hypothalamus, low-level information is extracted to emulate sensory data processing patterns. Subsequently, resembling the hippocampus, this information is processed at a higher level, capturing and memorizing correlated patterns. We conduct a comparative analysis of our model against existing quantum models such as Quantum Neural Networks and their classical counterparts, elucidating its unique contributions. Through empirical results, we aim to underscore the effectiveness of our approach in optimizing energy consumption in practical scenarios.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Economic sustainability of rural areas is a concern given the increasing trend towards urbanization globally and in India. Self-reliant strategies, including increased savings and investment are more valuable in this regard than external interventions. This paper uses the results of a survey to examine the factors affecting saving in a rural part of Odisha populated primarily by tribals. Our tentative findings are that savings propensity is determined partly by the extent to which individuals feel connected to the broader economy, and partly by cultural factors. One implication of these findings is that connecting rural areas to other, possibly urban, locations could elicit greater saving and this could lead to greater development, employment possibilities, economic betterment and all the consequent social welfare implications. This paper relates savings propensity to new sociological population characteristics, such as perceived connectivity and food consumption patterns, and hence provides hitherto unexplored clues for policy initiatives to increase savings.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.

Graph visualization has evolved significantly over time, offering various methods to effectively represent complex data structures. This study introduces a novel force-directed algorithm for 3D data visualization, specifically tailored for commonly used datasets in linked data visualization. Leveraging the power of graph theory and methods, the algorithm aims to address the challenge of creating visually appealing and easily interpretable visualizations, which often necessitate advanced user interaction. By utilizing 3D space and the Unity Engine, the research successfully visualizes data and develops interactive visualizations, overcoming limitations of basic force-directed implementations. The main contribution of presented research is in the force-directed algorithm with springs and controlled placement as a visualization technique that combines the use of springs and attractive forces to stabilize a graph in a 3D environment. The combination of these two techniques also helps prevent the formation of a single large cluster within the graph, enhancing the overall visualization quality.

Patients with underlying health conditions are at risk for a poor outcome from Coronavirus disease 2019 (COVID-19). Using machine reasoning by the sci.AI system, we investigated the pathobiochemistry of this observation to generate therapeutic guidelines. Facts were extracted and linked from publications available in nlm.nih.gov and Europe PMC to form the dataset which was validated by medical experts. Previously we described how preexisting chronic inflammation renders the acute inflammatory response to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) excessive translating the SARS-CoV-2 infection into the clinical COVID-19 syndrome. Herein we focus on therapeutic interventions that mitigate the immune response. In essence, from bench to bedside, as depicted in the Graphical Abstract, the clinical management of COVID-19 should aim at: A. Control of excessive oxidant production. B. Neutralization of excessive oxidants. C. Upregulation of nitric oxide (NO) production.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

This paper draws on data from a representative city-wide household food security survey of Nairobi conducted in 2017 to examine the importance of food remitting to households in contemporary Nairobi. The next section of the paper provides an overview of urbanization and the rapid growth of Nairobi which has led to growing socio-economic inequality, precarious livelihoods for the majority, and growing food insecurity, as context for the more detailed empirical analysis of food security and food remittances that follows. It is followed by a description of the survey methodology and sections analyzing the differences between migrant and non-migrant households in Nairobi. Attention then turns to the phenomenon of food remitting, showing that over 50% of surveyed households in the city had received food remittances in the previous year. The paper then uses multivariate logistic regression to identify the relationship between Nairobi household characteristics and the probability of receiving food remittances from rural areas. The findings suggest that there are exceptions to the standard migration and poverty-driven explanatory model of the drivers of rural-urban food remitting and that greater attention should be paid to other motivations for maintaining rural-urban connectivity in Africa.

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band oscillations as indicators of hypnotic states, alterations in EEG functional connectivity during hypnosis and wakefulness, drawing critical conclusions, and suggesting future research directions. The reviewed functional connectivity findings support the notion that disruptions in the functional integration between different components of the executive control network during hypnosis may correspond to altered subjective appraisals of the agency during the hypnotic response, as per dissociated and cold control theories of hypnosis. Building upon existing EEG results, a promising exploration avenue involves investigating how frontal lobes' integrated functioning with other cortical regions influences hypnosis and individual differences in hypnotizability during both waking and hypnotic states. Future studies investigating the effects of hypnosis on brain function should prioritize examining distinctive activation patterns across various neural networks. A practical approach entails simultaneously analyzing the causal relationships in functional connectivity linked to cognitive, physiological, and behavioral responses.

The Collatz conjecture is a well-known number theory puzzle that states that every positive integer would eventually converge to the trivial cycle of 1, 2, 1, 2,... when repeatedly exposed to a particular transformation. In this transformation, even numbers are divided in half, odd numbers are tripled, and one is added. In this study, we present a new method for creating a directed graph and using it to display and analyze Collatz sequences. Our technique creates what we call a Collatz directed graph by joining an endless number of simple directed graphs, each of which corresponds to a natural number. We show by careful mathematical analysis that all positive integers are included in this Collatz directed graph. Moreover, we give an evidence that verifies the Collatz conjecture by showing that the sole cycle in this graph is the trivial cycle of 1, 2, 1, 2,... We also prove that there is no sequence that diverges to infinity in this graph. Our results provide insights into the fundamental structure of Collatz sequences and further our knowledge of the Collatz conjecture .

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

We present a new computing package Flagser, designed to construct the directed flag complex of a finite directed graph, and compute persistent homology for flexibly defined filtrations on the graph and the resulting complex. The persistent homology computation part of Flagser is based on the program Ripser [2], but is optimised specifically for large computations. The construction of the directed flag complex is done in a way that allows easy parallelisation by arbitrarily many cores. Flagser also has the option of working with undirected graphs. For homology computations Flagser has an Approximate option, which shortens compute time with remarkable accuracy. We demonstrate the power of Flagser by applying it to the construction of the directed flag complex of digital reconstructions of brain microcircuitry by the Blue Brain Project and several other examples. In some instances we perform computation of homology. For a more complete performance analysis, we also apply Flagser to some other data collections. In all cases the hardware used in the computation, the use of memory and the compute time are recorded.

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.

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

In this work, the transport equations of ionic species in concrete are studied. First, the equations at the porescale are considered, which are then averaged over a representative elementary volume. The so obtained transport equations at the macroscopic scale are thoroughly examined and each term is interpreted. Furthermore, it is shown that the tortuosity-connectivity does not slow the average speed of the ionic species down. The transport equations in the representative elementary volume are then compared with the equations obtained in an equivalent pore. Lastly, comparing Darcy’s law and the Hagen-Poiseuille equation in a cylindrical equivalent pore, the tortuosity-connectivity parameter is obtained for four dierent concretes. The proposed model provides very good results when compared with the experimentally obtained chloride profiles for two additional concretes.

Many marine species use different habitats at different stages of their life cycle. Functional connectivity, the degree to which the seascape facilitates or impedes movement between habitat patches, is poorly studied in marine systems. We reviewed the scientific literature to explore the various barriers preventing functional connectivity between marine habitats and how the removal of these barriers may restore connectivity. To our knowledge, this is the first systematic review to investigate functional connectivity between life cycle habitats for a range of marine species. A total of 4,499 records were identified and screened, leaving 69 publications eligible for review. The results highlighted a range of distances between nursery and adult habitats that limited functional connectivity for a number of species, predominantly reef fishes. For some species, adults were absent on reefs >9km from the closest nursery habitat, suggesting a threshold for connectivity. Similarly, increased distance between spawning and settlement habitats decreased settling success of larvae of various taxa. Pelagic larval duration, seascape topography and climate change were also shown to impact functional connectivity during the larval phase. The removal and mitigation of barriers preventing functional connectivity, including dams and habitat fragmentation, restored connectivity between disconnected life cycle habitats, but the efficacy of these approaches differed between species and studies. The results of this review deepen our understanding of marine functional connectivity between life cycle habitats via larval, juvenile, and adult dispersal. These findings have implications for the design and management of marine reserve networks.

Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and is ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful and which can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P<0.05), left hippocampus volume (LHV, β: -0.02435, P<0.01) and right hippocampus volume (RHV, β: -0.02544, P<0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P<0.05) and LHV (β: -0.01173, P<0.05) and RHV (β: -0.01193, P<0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P<0.05; RHV, β: -0.005527, P<0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

Interhemispheric and frontoparietal functional connectivity have been reported to increase during explicit information processing. However, it is unclear how and when interhemispheric and frontoparietal functional connectivity interact during explicit semantic processing. Here, we tested the neural coupling hypothesis that explicit semantic processing promotes neural activity in the nondominant right hemispheric areas owing to synchronization with enhanced frontoparietal functional connectivity at later processing stages. We analyzed electroencephalogram data obtained using a semantic priming paradigm, which comprised visual priming and target words successively presented under direct or indirect attention to semantic association. Scalp potential analysis demonstrated that the explicit processing of congruent targets reduced negative event-related potentials, as previously reported. Current source density analysis showed that explicit semantic processing activated the right temporal area during later temporal intervals. Subsequent dynamic functional connectivity and neural coupling analyses revealed that explicit semantic processing increased the correlation between right temporal source activities and frontoparietal functional connectivity in later temporal intervals. These findings indicate that explicit semantic processing increases neural coupling between the interhemispheric and frontoparietal functional connectivity during later processing stages.

Green spaces in residential community is important, yet understudied, feature as an urban ecological system. While large urban parks and remnant wildlands in urban areas tend to receive a public attention from conservation and management perspectives, less is known for the importance of spatial and ecological characteristics of the community-scale landscapes. This study investigates natural elements in four planned communities in Phoenix metropolitan area, Arizona, two of which represent conventional type of neighborhood and the other two exemplify the community development with a proclaimed vision of sustainability. These distinct type of communities, which capture variations in age, location, open space type, and a cross-section of housing density, are compared with regard to landscape connectivity as a means of gauging ecological condition for community sustainability. Using Geographical Information System and landscape connectivity indices, each community’s landscape features including size, physical connectedness and ecological potential were examined. Furthermore, a questionnaire survey was performed to examine the perceptional differences between the two types of community residents. The findings demonstrate that the green spaces in conventional communities are more physically connected than the counterparts, but the naturalness and ecological quality manifested by the amount of the land that may serve as potential urban desert habitats were higher in the sustainable communities. The results of the survey indicated that the respondents inhabiting in sustainable communities possess a higher level of satisfaction than the people in conventional type of community due mainly to the amount of, easy access to, and perceived ecological values of, green spaces in their neighborhoods and surrounding areas. The study concludes that careful community design with ecological consideration can help create sustainable communities which can benefit both site-scale ecosystems and perceived human well-being.

Ecological connectivity, as a research method related to spatial ecology and conservation biology, has attracted increasing attention from researchers at home and abroad in recent years. Habitat connectivity, as a key link in ecological connectivity, is of great significance to promote offshore ecological restoration and protection. However, there has been less systematic research about habitat connectivity, which lacks corresponding theories and practices. Therefore, this paper discusses habitat connectivity from three aspects: (1) the concept of habitat connectivity is introduced and clarified, (2) the application of connectivity in artificial habitat and adjacent waters and its relationship with biodiversity conservation are reviewed and illustrated with examples, and (3) the future development trends of this research direction are summarized and prospected, in order to provide a scientific basis and useful reference for the related work of offshore restoration projects in China. Generally, this paper argues that an increase in human behavior irreversibly destroys the connectivity of marine habitats and threatens the temporal scales of biodiversity and ecosystem services. Therefore, the theoretical research results and practical experience of ecological connectivity should be fully applied to marine ecosystems, and the restoration of degraded ecosystems should be encouraged and supported in ways that promote natural recovery.

Background: Emergency medical services (EMS) are the first health care contact for the majority of stroke patients. However, there is a lack of data on the current paramedics’ hospital-directed feedback and training needs across different health care settings. We aimed to evaluate paramedics’ prehospital stroke care knowledge, training needs, and current status of feedback on suspected stroke patients. Methods: We surveyed paramedics from the Vilnius region from September to November 2019, and compared the answers between the city and the district agencies. The questionnaire content included questions on paramedics’ demographic characteristics, prehospital stroke care self-assessment, knowledge on stroke mimics, stroke training needs, and the importance of hospital-directed feedback on suspected stroke patients. Results: A total number of 161 paramedics were surveyed, with more district paramedics rating their prehospital stroke care knowledge as inadequate (44.8% (95% confidence interval (CI) 32.8–57.6) vs 28.1% (95% CI 20.1–27.8), p = 0.028). In addition, more district paramedics indicated a need for additional stroke training (83.1% (95% CI 71.5–90.5) vs 69.8% (60.0–78.1), p = 0.043). However, respondents reported being the most confident while dealing with stroke (71.3%, 95% CI 63.8–77.7) compared to other time-critical conditions (p < 0.001). Vertigo (60.8%, 95% CI 53.0–68.0), brain tumours (56.3%, 95% CI 48.5–63.8), and seizures (54.4%, 95% CI 46.7–62.0) were indicated as the most common stroke mimics. Only 6.2% (95% CI 3.4–11.1) of respondents received formal feedback on the outcome of suspected stroke patients brought to the emergency department. Conclusion: A high proportion of paramedics self-perceive having inadequate stroke knowledge and an urgent need for further stroke training. The EMS staff indicate receiving an insufficient amount of feedback on suspected stroke patients, even though the usefulness is perceived to be paramount.

We use binary string to represent a natural number and show the composite procedure of odd-number and even-number functions, thus we propose full binary directed tree to represent the set of natural numbers and give another partition the natural number set to three sets: pure odd, pure even and mixed number. For the Collatz conjecture we make use of the parity of a natural number to analyse the sequence of iteration (or composite) of Collatz function and reduced Collatz function analog to the inverse function. We give tabular and binary strings to the algebra expression to state the sequence of Collatz, this is the key topic to proof the conjecture: the discrete powers of 2 can be changed to ultimately continuous powers of 2, finally get to pure even number and to the smallest number 1. The sequence created by the infinite iterations of the Collatz function becomes the ultimately periodic sequence if any natural number is the beginning value, proving the conjecture that has been held for 87 years.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

The advent of deep learning (DL) has revolutionized medical imaging, offering unprecedented avenues for accurate disease classification and diagnosis. DL models have shown remarkable promise for classifying brain tumor from Magnetic Resonance Imaging (MRI) scans. However, despite their impressive performance, the opaque nature of DL models poses challenges in understanding their decision-making processes, particularly crucial in medical contexts where interpretability is essential. This paper explores the intersection of medical image analysis and DL interpretability, aiming to elucidate the decision-making rationale of DL models in brain tumor classification. Leveraging state-of-the-art DL frameworks with transfer learning, we conduct a comprehensive evaluation encompassing both classification accuracy and interpretability. Using state-of-the-art DL frameworks with transfer learning, we conduct a thorough evaluation covering both classification accuracy and interpretability. We employ adaptive path-based techniques to understand the underlying decision-making mechanisms of these models. Grad-CAM and Grad-CAM++ highlight critical image regions where the tumors are located.

The $k$-set tree connectivity, as a natural extension of classical connectivity, is a very important index to evaluate the fault-tolerance of interconnection networks. Let $G=(V, E)$ be a connected graph and a subset $S\subseteq V$, an $S$-tree of graph $G$ is a tree $T=(V',E')$ that contains all the vertices of $S$. Two $S$-trees $T$ and $T'$ are internally disjoint if and only if $E(T)\cap E(T')=\varnothing$ and $V(T)\cap V(T')=S$. The cardinality of maximum internally disjoint $S$-trees is defined as $\kappa_{G}(S)$, and the $k$-set tree connectivity is defined by $\kappa_{k}(G)=\min\{\kappa_{G}(S)|S\subseteq V(G)\ \text{and} \ |S|=k\}$. In this paper, we show that the $k$-set tree connectivity of hierarchical folded hypercube when $k=4$, that is, $\kappa_{4}(HFQ_{n})=n+1$, where $HFQ_{n}$ is hierarchical folded hypercube for $n\geq 7$.

This paper presents technical solutions to increase Industry 4.0 maturity. Within the “5G-Enabled Manufacturing” project, a 5G network has been deployed at the shop floor to enable fast and scalable connectivity. This network was used to connect a grinding machine to a private cloud to enable visibility and transparency of the production data, which is the basis for Industry 4.0 and smart manufacturing. Results indicate a present lack of commercially available product independent solutions for interconnection and data transfer despite the availability of open standards and well-documented demonstrator projects. The solution is described and discussed regarding technical interoperability, focusing on the system layout, communication standards, and open systems. From the discussion, it is derived that manufacturing end-users are in need to expand and further internalize knowledge on future information and communication technologies to reduce their dependency on equipment and technology providers.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

In the dynamic landscape of 6G and smart cities, Visible Light Communication (VLC) assumes critical significance for IoT (Internet of Things) applications spanning diverse sectors. The escalating demand for bandwidth and data underscores the need for innovative solutions, positioning VLC as a complementary technology within the electromagnetic spectrum. This paper focuses on the relevance of VLC in the 6G paradigm, shedding light on its applicability across smart cities and industries. The paper highlights the growing efficiency of lighting LEDs in infrastructure, facilitating the seamless integration of VLC. The study then emphasizes VLC’s robustness in outdoor settings, demonstrating effective communication up to 10 meters. This resilience positions VLC as a key player in addressing the very last meter of wireless communication, offering a seamless solution for IoT connectivity. By introducing an a freely available open-source simulator combined to an alternative waveform, UFMC, the study empowers researchers to dimension applications effectively, showcasing VLC’s potential to improve wireless communication in the evolving landscape of 6G and smart cities.

The research proposes a self-directed paradigm with self-design using the existing technology with LMS modules, discussions, and self-tests. The research establishes its criteria for assurance of teaching and learning known as 7x2C for the compliance of content, and appearance along with other criteria for the analysis. The above technology of web and LMS is tested for a business course that is technology-oriented in creating an experiential learning system for Covid-19 awareness. Similarly, among other ideas, an environment for educating learners about diabetes and obesity has been designed. The project is known as Sunchoke with its theme of Grow, Eat, and Heal. The educators can use their technology and apply self-directed pedagogy to transform this approach to their customized ways by using their content and rubrics.

Tumor heterogeneity is a major obstacle in cancer therapy. We offer a novel perspective on tumor heterogeneity, informed by expanding upon the current view on tumor evolution. It is commonly known that in cancer, it is the advantageous genes and mutations that drive tumor capacities and the progression. We recognize an earlier, often overlooked, but necessary thus crucial step preceding the activation of advantageous genes functionality, namely, cellular response. We suggest that cancer is driven by an adaptive action taken by any organism when confronted with adversity - a cellular response to generate specific cancer capacities demanded to overcome survival threat - the responses that prompt the utilization of the functionality of advantageous genetic mutations and genes to attain these capacities and drive the disease. The ongoing development of cancer capabilities, as cells endeavor to obtain a competitive advantage, results in increased molecular chaos, observed as tumor heterogeneity. When the evolutionary drive for survival is impeded by therapeutic inhibition of critical genes, cell death occurs, a phenomenon thus termed oncogene addiction. We summarize the implications of this new framework for understanding tumor evolution and anti-cancer drug discovery, as well as understanding of basic cancer biology.

In this work, oligoesters with terminal hydroxyl groups were obtained by directed glycolytic degradation of polyethylene terephthalate. The possibility of obtaining bifunctional reactive oligomers with an average molecular weight of 865 g mol-1 by directed glycolytic destruction via a dissolution-degradation strategy in dimethyl sulfoxide at a low concentration of ethylene glycol (32.3 mass parts per 100 mass parts of polyethylene terephthalate) was shown. This process allows us to partially solve the urgent problem of recycling post-consumer polyethylene terephthalate.

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed to symptoms relief, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from repurposing of specific compounds with known antiviral activity to the screening of libraries and of natural compounds. The identified antiviral candidates include drugs targeting viral components (structural proteins and enzymes), as well as cellular ones. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

Modularity is arguably one of the most influential theses guiding research on brain and cognitive function since phrenology. This paper considers the following question: is modularity entailed by recent Bayesian models of brain and cognitive function, especially the predictive processing framework? It starts by considering three of the most well-articulated arguments for the view that modularity and predictive processing work well together. It argues that all three kinds of arguments for modularity come up short, albeit for different reasons. The analysis in this paper, although formulated in the context of predictive processing, speaks to broader issues with how to understand the relationship between functional segregation and integration and the reciprocal architecture of the predictive brain. These conclusions have implications for how to study brain and cognitive function. Specifically, when cognitive neuroscience works within an acyclic Markov decision scheme, adopted by most Bayesian models of brain and cognitive function, it may very well be methodologically misguided. This speaks to an increasing tendency within the cognitive neurosciences to emphasise recurrent and reciprocal neuronal processing captured within newly emerging dynamical causal modelling frameworks. The conclusions also suggest that functional integration is an organising principle of brain and cognitive function.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

By defining a constant probabilistic orbit of and iterated functions, the stability dynamics of these functions in possible interactions through connectivity provides the formation of a dynamic fixed point as a metric space between both iterated functions. The presence of a dynamic fixed point identifies qualitatively phases of iteration time lengths and interaction orbits of the event. Qualitative results show that the greater the average distance from one of the functions to the fixed point of the other (all possible solutions), the higher the iteration expression on time (false asymptotic effect) of one of the functions and in the opposite hand, the lower the average distance, the higher orbit’s interactions proximity between iterated functions (stability). This feature reveals asymptotic (well-defined) behavior between functions f and g within a well-defined Lyapunov stability.

Amongst the advantages of using Worldwide Interoperability Microwave Access (WiMAX) technology at the last-mile level as access technology include an extensive range of 50 km Line of Sight (LOS), 5 to 15 km Non-Line of Sight and few infrastructure installations compared to other wireless broadband access technologies. Despite positive investments in ICT fibre infrastructure by developing countries, including Botswana, servicing end-users is subjected to high prices and service disparities. The alternative, the Wi-Fi hotspot initiative by the Botswana government, falls short as a solution for last-mile connectivity and access. This study used OPNET simulation Modeller 14,5 to investigate whether Botswana’s national broadband project could adopt WiMAX IEEE 802.16e as an access technology. Therefore, using the simulation method, this paper evaluates the WiMAX IEEE 802.16e/m over three subscriber locations in Botswana. The results obtained indicate that the deployment of the WiMAX IEEE 802.16e standard can solve most of the deployment issues and access at the last-mile level. Although the findings suggest that WiMAX IEEE 802.16e is more suitable for high-density areas, it could also solve rural areas’ infrastructure development challenges and provide the required high-speed connectivity access. However, unlike the Wi-Fi initiative, which requires more infrastructure deployment and less on institutional and regulatory frameworks, the deployment of WiMAX IEEE802.16e requires institutional and regulatory standards.

Introduction: Musculoskeletal dysfunctions happen to be the most common reason for referral to physiotherapy and manual therapy services. Therapists may use several articular and/or soft tissue concepts/approaches to evaluate and treat such dysfunctions that may include integration of myofascial system. Despite the research in this area spanning more than three decades, the role played by fascia has not received its duly deserved attention, owing to the lack of definitive research evidence. The concept of ‘fascial connectivity’ evolved two decades ago from a simple anatomical hypothesis called ‘myofascial meridians’. Since then it has been widely researched, as conceptually it makes more sense for functional movements than ‘single-muscle’ theory. Researchers have been exploring its existence and role in musculoskeletal dysfunctions and clinicians continue to practice based on anecdotal evidence. This narrative review attempts to gather available evidence, in order to support and facilitate further research that can enhance evidence based practice in this field. Methods: A search of most major databases was conducted with relevant keywords that yielded 272 articles as of December 2019. Thirty five articles were included for final review with level of evidence ranging from 3b to 2a (as per Center of Evidence Based Medicine’s scoring). Results: Findings from cadaveric, animal and human studies supports the claim of fascial connectivity to neighboring structures in the course of specific muscle-fascia chains that may have significant clinical implications. Current research (level 2) supports the existence of certain myofascial connections and their potential role in the manifestation of musculoskeletal dysfunctions and their treatment. Conclusion: Although these reviews and trials yield positive evidence for the objective reality/existence of fascial connectivity and continuity, several aspects need further exploration and in-depth analysis, which could not be evidenced entirely in this review. Manual and physical therapists may utilize the concept of fascial connectivity as a convincing justification to deal with clinical problems, but need to remain vigilant that functional implications are still being investigated.

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

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

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

Visual Sensor Networks (VSNs) have been the focus of numerous studies, emphasizing the quality of the information they generate. The primary goal of these networks is to capture data from an area, extract the pertinent information from the visual scene, and facilitate communication. However, the presence of objects in the study area can impacted the network's efficiency, linking the quality of acquired data directly to the positioning of the cameras. Strategically positioning multiple cameras in a potentially complex area, while ensuring effective communication between nodes, presents a challenging issue in VSNs applications. This paper introduces a specific method to enhance the deployment of visual sensors in indoor environments. The research addresses the theme of multi-objective optimization of VSN deployment, integrating various criteria: maximizing overall visual coverage, maximizing the observation of zones of interest, maximizing observation redundancy of zones of interest and ensuring communication connectivity for data transfers. To tackle this problem, we simulate the observed environment incorporating cameras, obstacles, and considering zones of interest. Camera positioning is performed while considering visual constraints and the scene's characteristics. The quality of positioning is evaluated based on the defined objective functions. Initially, a comparative study is conducted with a state-of-the-art approach, integrating the first three objective functions. Subsequently, we incorporate the fourth objective function to ensure data transfers. The proposed method demonstrates efficient camera network deployments in indoor areas, considering global coverage and observation redundancy. In contrast to the state-of-the-art, these results are achieved in areas with visual obstacles while ensuring communication connectivity between the different cameras.

Brain-computer interfaces (BCI) from electroencephalography (EEG) provide a practical approach to support human-technology interaction. In particular, motor imagery (MI) is a widely-used BCI paradigm that guides the mental trial of motor tasks without physical movement. Here, we present a deep learning methodology, named Kernel-based Regularized EEGNet (KREEGNet), leveled on Centered Kernel Alignment and Gaussian Functional Connectivity, explicitly designed for EEG-based MI classification. The approach proactively tackles the challenge of intra-subject variability brought on by noisy EEG records and the lack of spatial interpretability within end-to-end frameworks applied for MI classification. KREEGNet is a refinement of the widely accepted EEGNet architecture, featuring an additional kernel-based layer for regularized Gaussian functional connectivity estimation based on CKA. The superiority of KREEGNet is evidenced by our experimental results from binary and multi-class MI classification databases, outperforming the baseline EEGNet and other state-of-the-art methods. Further exploration of our model’s interpretability is conducted at individual and group levels, utilizing classification performance measures and pruned functional connectivities. Our approach is a suitable alternative for interpretable end-to-end EEG-BCI based on deep learning.

Topological indices are numerical parameters of a graph which characterize its topology and are usually graph invariant. In this paper, bounds for the Randić, general Randić, sum-connectivity, the general sum-connectivity and harmonic indices for tensor product of graphs are determined by using the combinatorial inequalities and combinatorial computing.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

Directed evolution methods are becoming increasingly popular, as they are extremely powerful toward developing new biomolecules with altered/novel activities, e.g., proteins with new catalytic functions or substrate specificities, and nucleic acids that recognize an intended target. Especially useful are systems that have incorporated continuous evolution, where the protein to be evolved undergoes continuous mutagenesis to evolve a desired trait with little to no input from the researcher once the system is started. However, continuous evolution methods can be challenging to implement in the lab and daunting for researchers to invest time and resources. Our intent is to provide basic information and helpful suggestions that we have gained from our experience with bacterial phage-assisted continuous evolution (PACE). Specifically, we review factors to consider before adopting PACE for a given evolution scheme, different types of selection circuits that can be utilized with particular focus on the PACE-B1H selection system, what optimization of a PACE selection circuit may look like using directed evolution of ME47 as a case study, and additional techniques that may be incorporated into a PACE experiment. With this information, researchers will be better equipped to determine if PACE is a valid strategy to use to evolve their proteins and how to set up a valid selection circuit.

Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.

The main purpose of this article is to identify brain diseases such as Alzheimer's and Parkinson's in an intelligent way using Python software and processing the function of neurons in the neural network areas of the brain, which are classified into different components, and the data is based on the information obtained from FMRI images using algorithms artificial intelligence can intelligently diagnose the type of disease. Therefore, by using spatial clustering based on the deep learning method with noise algorithm (DBSCAN), fMRI brain image and fMRI brain surface complexity are classified, and then image preprocessing will be applied to fMRI images by using artificial intelligence neural networks (ANN) algorithm. became. Then, by using the ANN algorithm and Deep CNN topology of the brain neural network, the type of disease in the brain can be diagnosed by simulating the performance of an artificial neural network (ANN) in Python software. Deep machine learning-based methods, especially algorithms based on neural networks, have shown great success in medical image analysis for various tasks including brain tumor detection, segmentation, and classification, and Alzheimer's and epilepsy. In this research, we propose an integrated model based on a convolutional neural network for simultaneous recognition and classification of brain diseases for intelligent diagnosis of tumors and epilepsy. The average accuracy obtained from our proposed model is 97.89 percent accuracy and 91.66 percent specificity.

This study presents a computational simulation to explore the distinctive patterns of neural connectivity in Autism Spectrum Disorder (ASD), focusing on the concepts of spatial and topological proximities. ASD is characterized by unique cognitive and behavioral profiles, often attributed to atypical neural development and connectivity. Our simulation employs a two-pronged approach: first, by modeling spatial proximity through the generation of clustered 3D node positions, we mimic the observed over-connectivity in localized brain regions in ASD. Second, we construct a topological network to represent the complex interplay of under-connectivity and over-connectivity in functional brain networks, a hallmark of ASD's neural landscape. The spatial model demonstrates pronounced clustering, reflecting the structural brain differences and atypical growth patterns reported in neuroimaging studies of individuals with ASD. In contrast, the topological model reveals a network with a mix of sparse and dense connections, simulating the diverse and often contradictory findings of functional connectivity in ASD, such as reduced long-range connections and increased local connections. Our simulation provides a visual and conceptual framework for understanding the altered neural connectivity in ASD. It underscores the importance of considering both physical (spatial) and functional (topological) aspects of brain connectivity to grasp the full extent of neurodevelopmental deviations in ASD. This approach not only aids in elucidating the neural underpinnings of ASD's core symptoms but also offers a foundation for developing targeted interventions. Future research, integrating more complex and individual-specific data, could further refine this model, enhancing our understanding of ASD's neural dynamics and contributing to personalized therapeutic strategies.

The connectivity level of last-generation vehicles is constantly on the rise. The combined use of Vehicle-To-Everything (V2X) connectivity and autonomous driving can provide remarkable benefits through the optimization of the route and speed trajectory. In this framework, this paper focuses on vehicle eco-driving optimization in a connected environment. The virtual test rig of a premium segment passenger car was used for generating the simulation scenarios. The benefits, in terms of energy and time savings, that the introduction of V2X communication, integrated with cloud computing, can have in a real-world scenario were assessed. The Reference Scenario is a pre-defined Real Driving Emissions (RDE) compliant route, while the simulation scenarios were generated by assuming two different penetration levels of V2X technologies. The associated energy minimization problem is formulated and solved by means of a global optimization algorithm, i.e., Dynamic Programming (DP). The optimization framework includes information coming from the surrounding environment, e.g., traffic lights state, speed limits, distance to travel, etc. The simulations show that introducing a smart infrastructure along with optimizing the vehicle speed in a real-world route can potentially reduce the required energy by 54% while shortening the travel time by 38%. Finally, a sensitivity analysis is performed on the bi-objective optimization cost function to find a set of Pareto optimal solutions, between energy and travel time minimization.

Background Content marketing is increasingly important for online branding. Brand popularity can be more easily determined online than sales-based measures but is not yet well-explained from a content marketing perspective. Promising predictors are open data syndication policies, connectivity to e-commerce platforms, product reviews, data health, and the depth and width of a brands product portfolio. A predictive content marketing model can help brand owners to understand their e-commerce potential. Methods We used brand popularity (Brand Popularity Rank) and catalog data in combination with product reviews from an independent content aggregator. For all datasets, we selected the overlapping dataset for brand popularity and brand reviews based on a period of 90 days from June 10, 2022, till September 24, 2022 (n = 333 brands). Backward stepwise multiple linear regression was used to develop a predictive content marketing model of the Brand Popularity Rank. Results Through stepwise backward multiple linear regression five highly significant (p < 0.01) predictive factors for brand rank are selected in our content marketing model: the brand’s data syndication policy, the number of connected e-commerce platforms, a brand’s number of products, its number of products per category, and the number of product categories in which it is active. Our model explains 78% of the variance of Brand Popularity Rank and has a good and highly significant fit: F (5, 327) = 233.5, p < 0.00001. Conclusions We conclude that a content marketing model can adequately predict a Brand Popularity Rank based on online popularity. In this model an open content syndication policy, more connected e-commerce platforms, and catalog size, i.e., presence in more categories and more products per category are each related to a better (lower) Brand Popularity Rank score.

The study of the brain networks using analysis of electroencephalography (EEG) data based on statistical dependencies (functional connectivity) and mathematical graph theory concepts is common in neuroscience and cognitive sciences for examinations of patient and healthy individuals. The Consciousness Fields according to Taheri theory and applications in the optimization of system under study have been investigated in various studies. In this study, we examine the results of working with Faradarmani Consciousness Field (FCF) in the brain of Faradarmangars. Faradarmangars are one of the necessary components in mind mediation of the function of Faradarmani Consciousness Fields according to Taheri. For this purpose, the functional and effective connectivity and the corresponding brain graphs of EEG from the brain of Faradarmangars is compared with that of non Faradarmangar groups during FCF connection. According to the results of the present study, the brain of the Faradarmangars shows significant decreased activity in delta (BA8), beta2 (BA4/6/8/9/10/11/32/44/47) and beta3 (in 34 of 52 BA) frequency bands mainly in frontal lobe and after that in parietal and temporal lobes in the comparison with the non Faradarmangars. Moreover, the functional and effective connectivity analysis in the frontal network shows dominant multiple decreased connectivity mainly in the case of beta3 frequency band in all parts of the frontal network. On the other hand, the graph theory analysis of the Faradarmangar brain shows an increase in the activity of the O2-T5-F4-F3-FP2-F8 areas and significant decrease in the characteristic path length and increases in global efficiency, clustering coefficient and transitivity. In conclusion, the unique higher graph function efficiency and the reduction in the brain activity and connectivity during the Faradarmani Consciousness Field mind mediation, shown the passive and detector like function of the human brain in this task.

We construct hypergraphs to analyze functional brain connectivity, leveraging event-related coherence in magnetoencephalography (MEG) data during the visual perception of a flickering image. Principal network characteristics are computed for delta, theta, alpha, beta, and gamma frequency ranges. Employing a coherence measure, a statistical estimate of correlation between signal pairs across frequencies, we generate edge time series, depicting how an edge evolves over time. This forms the basis for constructing an edge-to-edge functional connectivity network. Emphasizing hyperedges as connected components in an absolute-valued functional connectivity network, we focus on exploring these hyperedges in the context of individual variability. Our coherence-based hypergraph construction specifically addresses functional connectivity among four brain lobes: frontal, parietal, temporal, and occipital. This approach enables a nuanced exploration of individual differences within diverse frequency bands, providing insights into the dynamical nature of brain connectivity during visual perception tasks. The results furnish compelling evidence supporting the hypothesis of cortico-cortical interactions occurring across varying scales. The derived hypergraph illustrates robust activation patterns in specific brain regions, indicative of their engagement across diverse cognitive contexts and different frequency bands. Our findings suggest potential integration or multifunctionality within the examined lobes, contributing valuable perspectives to our understanding of brain dynamics during visual perception.

Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations(PD-H), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, the functional connectivity (FC) between cognitive sub-regions of the cerebellum of PD patients with hallucinations needs to be further clarified. Resting-state functional magnetic resonance imaging (rs-fMRI) data from three groups (17 PD-H, 13 no hallucinations accompanying the (PD-NH), and 26 healthy controls (HC) ) was collected in this study to explore the role of cerebellar FC changes in the cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machine(SVM). We found that PD-H patients' cerebellum(Vermis_4_5 ) FC had increased within the left side of the precuneus(PCUN) compared to HC, cerebellum(Vermis_1_2) had increased within bilateral opercular part of the inferior frontal gyrus(IFGoprec) and triangular part of the inferior frontal gyrus(IFCtriang), left side of postcentral gyrus(PoCG), Inferior parietal lobe(IPL), and PCUNs compared to PD-NH. In the training results of machine learning, cerebellar FC has also been proven to be an effective biomarker feature, with a recognition rate of over 90% for PD-H. These findings indicate that cortico-cerebellar FC in PD-H and PD-NH patients were significantly disrupted with different distributions. The proposed pipeline offers a promising low-cost alternative for the diagnosis of preclinical PD-H and can be useful for other degenerative brain disorders.

Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.

Electroencephalograms (EEGs) of children with reading disorder (RD) are characterized by higher power and coherence in slow frequencies (delta and theta bands) and lower power and coherence in the alpha band compared to EEGs of typically developed children. Neurofeedback (NFB) is useful for treating learning disorders by reinforcing the reduction of the theta/alpha ratio. This efficacy is supported by EEG power normalization and cognitive-behavioral improvement. To further explore brain changes in isolated areas, this study aimed to explore the effects of this NFB protocol on functional connectivity (coherence) in children with RD. Twenty children with RD and an abnormally high theta/alpha ratio underwent 30 sessions of NFB. After treatment, 90% of par-ticipants learned to decrease their theta/alpha ratio, and on average, children increased their reading accuracy and comprehension scores. Interhemispheric coherence diminished in the delta, theta and beta bands, mainly between frontopolar regions. Intrahemispheric coherence decreased in delta, theta and beta bands and increased in alpha band. The reduction in theta coherence be-tween the left frontal area and other regions of the left hemisphere had particular relevance for reading. These results suggest that this NFB treatment could positively impact reading-related functions in the brain networks of children with RD.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

A recent study demonstrated that noninvasive measurements of cortical hemodynamics and metabolism in the resting human prefrontal cortex can facilitate quantitative metrics of unilateral mitochondrial-hemodynamic coupling and bilateral connectivity in infraslow oscillation (ISO) frequencies in young adults (YA). The ISO includes three distinct vasomotions with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. The goal of this study was to prove the hypothesis that there are significant differences between young and older adults (OA) in the unilateral coupling (uCOP) and bilateral connectivity (bCON) in the prefrontal cortex. Accordingly, we performed measurements from 24 OA (67.2 ± 5.9 years of age) using the same 2-channel broadband near-infrared spectroscopy (bbNIRS) setup and resting-state experimental protocol as those in the recent study (Shahdadian et al, Cerebral Cortex Communications, 2022). After quantification of uCOP and bCON in three E/N/M frequencies and statistical analysis, we demonstrated that OA had significantly weaker bilateral hemodynamic connectivity but significantly stronger bilateral metabolic connectivity than YA in the M band. Furthermore, OA exhibited significantly stronger unilateral coupling on both prefrontal sides in all E/N/M bands, particularly with a very large effect size in the M band (&gt; 1.9). These age-related results clearly support our hypothesis and were well interpreted following neurophysiological principles. The key finding of this paper is that the neurophysiological metrics of uCOP and bCON are highly associated with age and may have the potential to become meaningful features for human brain health and be translatable for future clinical applications, such as early detection of Alzheimer’s disease.

In an era of global connectivity, language and literature education faces the challenge of navigating multilingualism, cultural diversity, and technological advancements. This paper explores the challenges and opportunities in language and literature education in the era of global connectivity. Through a qualitative research approach, interviews, focus group discussions, and classroom observations were conducted with 30 Arts and Sciences students and teachers. The findings reveal significant themes related to cultural diversity, multilingualism, and the integration of technology in language learning. The study emphasizes the importance of inclusive pedagogies, critical thinking development, and the incorporation of authentic and diverse literary works. Recommendations are provided for educators and policymakers to promote intercultural understanding and enhance language and literature education. The limitations of the study suggest areas for future research, including long-term language proficiency and diverse contextual considerations. Overall, this paper calls for ongoing innovation and collaboration to meet the evolving needs of language and literature education in an interconnected world.

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organised by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organisation and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organisation, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibres, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organisation and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

Deploying UAVs as aerial base stations is an exceptional approach to reinforce terrestrial infrastructure owing to their remarkable flexibility and superior agility. However, it is essential to design their flight trajectory effectively to make the most of UAV-assisted wireless communications. This paper presents a novel method for improving wireless connectivity between UAVs and terrestrial users through effective path planning. This is achieved by developing a goal-directed trajectory planning method using active inference. First, we create a global dictionary using TSPWP instances executed on various training examples. This dictionary contains letters representing available hotspots, tokens representing local paths, and words depicting complete trajectories and hotspot order. By using this world model, the UAV can understand the TSPWP’s decision-making grammar and how to use the available letters to form tokens and words at various levels of abstraction and time scales. With this knowledge, the UAV can assess encountered situations and deduce optimal routes based on the belief encoded in the world model. Our proposed method outperforms traditional Q-learning by providing fast, stable, and reliable solutions with good generalization ability.

Directed movement towards a target requires spatial working memory, including processing of sensory inputs and motivational drive. In a stimulus-driven, operant conditioning paradigm designed to train zebrafish, we present a pulse of light via LED’s and/or sounds via an underwater transducer. A webcam placed below a glass tank records fish swimming behavior. During operant conditioning, a fish must interrupt an infrared beam at one location to obtain a small food reward at the same or different location. A timing-gated interrupt activates robotic-arm and feeder stepper motors via custom software controlling a microprocessor (Arduino). “Ardulink”, a JAVA facility, implements Arduino-computer communication protocols. In this way, full automation of stimulus-conditioned directional swimming is achieved. Precise multi­day scheduling of training, including timing, location and intensity of stimulus parameters, and feeder control is accomplished via a user-friendly interface. Our training paradigm permits tracking of learning by monitoring, turning, location, response times and directional swimming of individual fish. This facilitates comparison of performance within and across a cohort of animals. We demonstrate the ability to train and test zebrafish using visual and auditory stimuli. Current methods used for associative conditioning often involve human intervention, which is labor intensive, stressful to animals, and introduces noise in the data. Our relatively simple yet flexible paradigm requires a simple apparatus and minimal human intervention. Our scheduling and control software and apparatus (NemoTrainer) can be used to screen neurologic drugs and test the effects of CRISPR­-based and optogenetic modification of neural circuits on sensation, locomotion, learning and memory.

The origins of directed acyclic graphs (DAGs) date back to the emergence of ‘graph theory’ in the early 1700s (Biggs et al. 1986). DAGs are conceptual or literal, diagrammatic representations of causal paths between variables which are constructed – as their name suggests – on the basis of two over-riding principles: first, that all causal paths are ‘directed’ (i.e. for each pair of variables, only one can represent the cause, while the other must be its consequence); and second, that no direct cyclical paths, or indirect cyclical pathways (comprising sequences of consecutive paths) are allowed, such that no consequence can be considered its own direct or indirect cause (hence ‘acyclic’; Law et al., 2012). As such DAGs reflect the knowledge, presumptions, assumptions and/or speculation of the analyst(s) concerned regarding the causal relationships between each of the variables included therein. Current convention dictates that variables are represented as nodes/vertices, and that any causal paths between variables are represented as directed arcs/edges/lines, often in the form of arrows (see Figure 1). Although each arc indicates the presence and direction of a known/presumed/assumed/speculative causal relationship between the two variables concerned, drawing an arc does not require the sign, magnitude, precision or shape of the relationship to be known or declared (Tennant et al., 2021). In this respect, DAGs provide a simple, uncomplicated, accessible and entirely nonparametric approach for postulating causal relationships amongst any variables of interest even when these are uncertain, unknown or entirely speculative (Ellison, 2020). Nonetheless, as a result of the parametric constraints imposed by the presence/absence of possible arcs within any given DAG, these also reflect and support a number of more sophisticated statistical applications which make it possible to use DAGs to inform the design of multivariable statistical models that reflect the causal structure(s) involved – albeit without the need to know or understand the mathematical technicalities on which these are based (Lewis and Kuerbis, 2016). These features make DAGs attractive cognitive, educational and analytical tools for strengthening the epistemological, theoretical and empirical basis of causal inference, and there has been a recent proliferation in the use of DAGs across a range of applied scientific disciplines (e.g. Knight and Winship, 2013), and an associated upsurge in analytical methods training (e.g. Elwert, 2011; Gilthorpe, 2017; Hernán 2018; Roy, 2021; Hünermund, 2021). This Chapter reflects on a decade of delivering medical statistics training to undergraduate medical students at the University of Leeds between 2012-2021 in which the third year research, evaluation and special studies module (‘RESS3’) has used DAGs to support the development of applied statistical skills relevant to the extended student-selected research and evaluation projects (ESREP) students undertake in their fourth and final years (Ellison, 2021; Ellison et al., 2014a,b). Based on successive iterations of the structure and content of the RESS3 module, together with notes made during formal and informal planning and review meetings with module leads, lecturers, tutors and students, we draw on the claims and criticisms made of DAGs in the epidemiological literature to identify a number of explicit strengths (and associated, often implicit. weaknesses) that are central to their use in prediction and causal inference modelling. While using DAGs requires (and benefits from) a clear understanding of their non-parametric nature and parametric implications, the weaknesses of DAGs seem likely to reflect both: the challenges inherent in the modelling of data generating processes when these are imperfectly understood; and troublesome cognitive and heuristic tendencies common to all analytical tools – in which the tool facilitates the task in hand by reducing the necessity (and benefits of) exploring uncertainties and identifying assumptions. These, more epistemological considerations appear particularly challenging for medical undergraduates to grasp (Ellison, 2021), but also appear poorly understood by many established analysts and clinical epidemiologists (Ellison, 2020).

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Breast cancer brain metastasis (BCBM) is a challenging condition with limited treatment options and poor prognosis. Understanding the interactions between tumor cells and the blood-brain barrier (BBB) is critical for developing novel therapeutic strategies. One promising target is estrogen receptor β (ERβ), which promotes the expression of key tight junction proteins, sealing the BBB and reducing its permeability. In this study, we investigated the effects of 17β-estradiol (E2) and the selective ERβ agonist diarylpropionitrile (DPN) on endothelial and cancer cells. Western blot analysis revealed the expression patterns of ERs in these cell lines, and estrogen treatment upregulated claudin-5 expression in brain endothelial cells. Using in vitro models of the BBB, we found that DPN treatment significantly increased BBB tightness about suppressed BBB transmigration activity of representative HER2-positive (BT-474) and triple-negative (MDA-MB-231) breast cancer cell lines. However, the efficacy of DPN treatment decreased when cancer cells were pre-differentiated in the presence of E2. Our results support ERβ as a potential target for the prevention and treatment of BCBM and suggest that targeted vector-based approaches may be effective for future preventive and therapeutic implications.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

Hashimoto’s thyroiditis (HT) is a common autoimmune disease, with its prevalence rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed features of HT through bioinformatics analysis so as to identify markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed Gene Set Enrichment Analysis (GSEA) using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. GSEA results revealed activation of autoimmune disease-related pathways and several viral infection pathways. Autoimmune disease and viral infection pathways were highly interconnected by common genes, while the HLA genes which are shared by both were significantly upregulated. CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor, which responds to viral activity, might serve as potential marker of HT.

Novel therapies for treatment of familial dilated cardiomyopathy (DCM) are lacking. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment which over time result in structural and functional maladaptations leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly in relation to mutant proteins and their impact on sarcomere molecular signaling, are currently the subject of controversy. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon Ca-activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale x-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering control of tension. We discuss these mechanisms that lead to different ideas related to how tension is controlled and disturbed by mutant sarcomere proteins linked to DCM including cardiac myosin, myosin-binding protein C, titin filaments, and thin filaments. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.

The contemporary landscape of education is witnessing a paradigm shift towards innovative instructional methods, with the flipped learning approach gaining considerable attention. The purpose of this research was to investigate the impact of the flipped learning approach on students' perception and acceptance throughout an entire semester in the 'Introduction to Programming with Java' course, using a research design with a quantitative approach, ultimately aiming to inform educational practice and advance our knowledge of innovative teaching methods in higher education. This study was conducted at a university with 174 students involved, divided into two groups, 87 students in the experimental group and 87 students in the control group. The data collected through the scales were analyzed by using descriptive and inferential statistical analysis techniques in statistical software. At the end of the measurements, the technology acceptance level and self-directed learning perceptions of engineering students who received education with flipped learning were high. The results suggest that educators should consider students' readiness for self-directed learning when implementing the flipped learning approach and focus on creating an environment that supports their autonomy and engagement. This research offers valuable guidance for instructors, curriculum designers, and educational policymakers seeking to enhance the effectiveness of flipped learning in higher education courses.

Background: Role-playing is often used as a pedagogical method for learning communication in medical education. Therefore, medical play using the Teddy Bear Hospital (TBH) is a concept that can quickly familiarize children with health care and help them develop positive experiences in these areas. This review aims to assess the strengths of TBH, as a form of directed medical role play, in improving health outcomes and well-being in children, along with implanting an awareness of preventive health care in young children.Methods: For this scoping review, we examined the list of recommendations, including 11 studies from two databases, PubMed and Google Scholar. We incorporated pre/post quasi-experimental studies, ANOVA, qualitative research studies, systematic reviews, and control group studies that deliberately utilize the teddy bear hospital as an intervention.Results: The results of individual studies were further categorized into three sections. The first being upon the analysis of 11 studies, the Teddy Bear Hospital was mainly conducted in Europe and Asia. It is evident that regardless of the different approaches and strategies used to implement the Teddy Bear Hospital, they all ultimately share the same intent: to raise health care awareness and alleviate young children's anxiety over medical treatment while focusing on the promotion of positive healthy lifestyle. All studies portray the teddy bear hospital as an intervention of medical roleplay which analyzed the children's feelings, behaviors, and health awareness after visiting the Teddy Bear Hospital.Conclusion: The application of the teddy bear hospital has overwhelmingly positive results, with lower levels of anxiety and improved health knowledge. Its reported efficacy calls for future studies on aspects that lead to its efficacy and potential effectiveness.

Lipid nanoparticles (LNPs) are promising carriers for constructing drug delivery systems (DDSs) in disease treatments. Previous studies have suggested that lipid composition and biophysical properties of LNPs can significantly impact their interaction with cells and tissues, allowing for the development of suitable LNPs for precise drug delivery. Our previous study proposed the concept and facile preparation of reconstituted lipid nanoparticles (rLNPs), which not only have the advantages of traditional LNPs but also contain the lipids of mother cell/tissue. In this study, we have found that brain-derived rLNPs (B-rLNPs) can have much better accumulation to the ischemic area of the ischemic stroke (IS) model than liver-derived rLNPs (L-rLNPs). This homing effect hopefully makes rLNPs a useful tool for developing highly accessible devices with homologous targeting ability for precise drug delivery.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

Hydrochemical and geophysical data collected during a hydrological survey in September 2017, reveal patterns of small-scale hydrological connectivity in a small water track catchment, north-European Arctic. Elevated tundra patches underlain by sands were disconnected from the stream and stored precipitation water from previous months. At the catchment surface and in the water track thalweg, some circular hollows, from 0.2 to 0.4 m in diameter, acted as evaporative basins with low d-excess values, from 2 to 4‰. Other hollows were connected to shallow subsurface runoff, yielding d-excess values between 12 and 14‰. ‘Connected’ hollows yielded a 50% higher dissolved organic carbon (DOC) content, 17.5±5.3 mg/L, than the ‘disconnected hollows, 11.8±1.7 mg/L. Permafrost distribution across the landscape is continuous, but highly variable. Open taliks exist under fens and small hummocky depressions, as revealed by electric resistivity tomography surveys. Isotopic evidence supports upward subpermafrost groundwater migration through open taliks under water tracks and fens/bogs/depressions, and its supply to streams via shallow sub-surface compartment. Temporal variability of isotopic composition and DOC in water track and a major river system, the Vorkuta R., evidence the widespread occurrence of the described processes in the large river basin. Water tracks effectively drain the tundra terrain and maintain xeric veg-etation over the elevated inter-track tundra patches.

Laser-Powder Directed Energy Deposition (DED-LB/Powder) is an additive manufacturing process that is gaining popularity in the manufacturing industry due to its numerous advantages, particularly in repairing operations. However, its application is often limited to case studies due to some critical issues that need to be addressed, such as the degree of internal porosity. This paper investigates the effect of the most relevant process parameters of the DED-LB/Powder process on the level and distribution of porosity. Results indicate that, among the process parameters examined, porosity is less affected by travel speed and more influenced by powder mass flow rate and laser power. Additionally, a three-dimensional finite element transient model was introduced, which was able to predict the development and location of lack-of-fusion pores along the building direction.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyses, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Liver receptors X α and β as well as Peroxisome proliferator-activated receptors α and γ. In this study fort the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.