Neuroscience has overwhelmingly and understandably focused on the synaptic modality of signal transmission. There is evidence, however, that from an evolutionary perspective, non-synaptic transmission (NST) preceded synaptic signaling. Moreover, in modern nervous systems, NST coexists and extensively interacts with synaptic transmission modifying neuronal dynamics. In fact, NST remains widespread in complex animals, especially within the interoceptive system where the dearth of insulating barriers such as myelin sheaths and the blood-brain barrier enhances the communication between neural and non-neural tissues mediated by NST. We suggest that this physiological arrangement makes a fundamental contribution to interoception¾the process of sensing visceral states¾which is an essential underpinning of the capacity to feel and the foundation of affective processing.

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes to a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure under the above described constraints.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

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

Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was detected also for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86 and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light-chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429 and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in D. melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long Term Potentiation (LTP) and Long Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses, the ability to easily undergo NMDA-mediated LTP and LTD, that is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results pinpoint to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of few, key, molecular interactions typical of structural biology ones.

The autosomal recessive disorder Ataxia-Telangiectasia is caused by dysfunction of the stress response protein ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumor risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies the cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits by bone-marrow transplantation, and reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated ATM depletion to trigger upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently neuropeptide machinery, e.g. Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM localized only to cytoplasm, similar to brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient / oxidative stress, not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

The continuous advancement of Artificial Intelligence (AI) technology depends on the efficient processing of unstructured data, encompassing text, speech, and video. Traditional serial computing systems based on the von Neumann architecture, employed in information and communication technology development for decades, not suitable for the concurrent processing of massive unstructured data tasks with relatively low-level operations. As a result, there arises a pressing need to develop novel parallel computing systems. Recently, there has been a burgeoning interest among developers in emulating the intricate operations of the human brain, which efficiently processes vast datasets with remarkable energy efficiency. This has led to the proposal of neuromorphic computing systems. Of these, Spiking Neural Networks (SNNs), designed to closely resemble the information processing mechanisms of biological neural networks, are subjects of intense research activity. Nevertheless, a comprehensive investigation into the relationship between spike shapes and Spike-Timing-Dependent Plasticity (STDP) to ensure efficient synaptic behavior remains insufficiently explored. In this study, we systematically explore various input spike types to optimize the resistive memory characteristics of Halfnium-based Ferroelectric Tunnel Junction (FTJ) devices. Among the various spike shapes investigated, the square-triangle (RT) spike exhibited good linearity and symmetry, and a wide range of weight values could be realized depending on the offset of the RT spike. These results indicate that the spike shape serves as a crucial indicator in the alteration of synaptic connections, representing the strength of the signals.

In the context of autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) plays a key role as biomarker of disease progression and response to therapy and has been recently recognized as enrichment biomarker and possible surrogate endpoint. Several imaging modalities and methods are available to calculate TKV, and the choice depends on the purpose of use. Technological advancements have made it possible to accurately assess cyst burden, that can be crucial to assess the disease state and help identifying rapid progressors. Moreover, the development of automated algorithms has increased the efficiency of total kidney and cyst volume measurements. Beyond total kidney and cyst volume, the quantification and characterization of non-cystic kidney tissue show potential to early stratify ADPKD patients, monitor disease progression, and possibly predict renal function loss. A broad spectrum of kid-ney MRI techniques are available to characterize kidney tissue, showing promise to non-invasively pick up early signs of ADPKD progression. Radiomics has been used to extract tex-tural features from ADPKD images, providing valuable information about the heterogeneity of the cystic and non-cystic components. This review provides an overview of ADPKD imaging bi-omarkers, focusing on quantification methods, potential, and necessary steps towards successful translation to clinical practice.

A supply chain management (SCM) system is a strategic cooperative that organically integrates all supply chains to improve the performance of a company. The greatest critical success factor of SCM is partnership. Without cooperation between companies, SCM performance is limited. Does this imply, therefore, that companies within the supply chain can achieve mutual transactions equally? If the power between companies is unequal, how does this affect their partnership? The focus of this study is to assess whether power types enhance SCM performance through partnerships. We categorize power types as mediated and non-mediated. Mediated power is categorized based on coercion, reward, and legitimate, while non-mediated power is categorized based on information, expert, and reference. Therefore, this study examines how power types form a causal partnership relationship within the supply chain, and performs an empirical investigation on how the partnerships influence SCM performance.

We consider open non-twist Hamiltonian systems represented by an area-preserving two-dimensional map describing incompressible planar flows in the reference frame of a propagating wave, and possessing exits through which map orbits can escape. The corresponding escape basins have a fractal nature that can be revealed by the so-called basin entropy, a novel concept developed to quantify final-state uncertainty in dynamical systems. Since the map considered violates locally the twist condition, there is a shearless barrier that prevents global chaotic transport. In this paper we show that it is possible to determine the shearless barrier breakup by considering the variation of the escape basin entropy with a tunable parameter.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

The main sources of intrinsic noise in excitable cells at the microcircuit and network levels are the stochastic characteristics of ion channel gating and activation of the synaptic conductance. Studies using in vivo, in vitro, and in silico methods to examine the effects of synaptic background activity were not adequately investigated in non-neuronal excitatory cells, where neurotransmitter-based innervation also occurs. We created a mathematical model to replicate the background synaptic noise dynamics in a non-neuronal cell. We utilized the stochastic Ornstein-Uhlenbeck process to represent excitatory synaptic conductance, which was incorporated into a whole-cell model to produce spontaneous and evoked cellular electrical activities. The single-cell model includes many biophysically detailed ion channels represented by a set of ordinary differential equations in Hodgkin-Huxley and Markov formalisms. This paradigm effectively induced irregular spontaneous depolarizations (SDs) and spontaneous action potential (sAP) resembling in vitro-like electrical activity in the cells. The input resistance decreased by multiple factors, and the spontaneous action potential firing rate elevated. The potential to reach the action potential threshold is altered. Background synaptic activity can alter the input/output characteristics of non-neuronal excitatory cells. Suppressing these baseline activities would facilitate the discovery of new pharmaceutical targets for different clinical diseases.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

The expanding use of devices emitting Pulsed Telecommunication Signals (PTS) has launched a serious debate over the possible effects of electromagnetic radiation (EMR) on living organisms. Our previous work has indicated that PTS exposure alters Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) metabolism in human cells of neural origin, providing a possible connection between exposure and neurodegeneration. This investigation aimed to reveal, in vitro in human non-neural cells (HEK293), the aftermath of the same exposure on the processing of APP and α-syn. Data presented here, indicate changes in APP metabolism, acquisition of different cellular topologies of the newly generated APP fragments, changes in monomeric α-syn accumulation and multimerization, indicating that APP and α-syn processing is possibly altered in the periphery by EMR. These effects are accompanied by a substantial increase in the levels of Reactive Oxygen Species (ROS). Further investigation is required in order to provide insights into the interaction of PTS with non-neural cells affecting the peripheral systemic functional stability. This is necessary because nowadays whole body human exposure from various EMR sources is a fact in normal life with the valid estimation that they may be increased in view of the forthcoming 5G telecommunications network implementation.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, high-dose Cy exposure can cause nerve injury with symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor ability. Moreover, it was found that medium- and high-dose Cy exposure can cause disordered energy metabolism in hippocampal cells and an abnormal release of the neurotransmitter Glu. Second, pathological brain sections showed that the middle and high doses of Cy caused deformation, reduction and disorder of hippocampal pyramidal cells, a decrease in the number of Nissl bodies, pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, with the increase in exposure dose, the morphological changes in hippocampal synapses were more obvious, including blurred synaptic spaces, decreased synaptic vesicles and a decreased number of synapses. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus, and the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators, inflammatory factors, synaptic plasticity factors and apoptosis factors, suggesting that Cy may cause nerve damage in rats and has a close relationship with A2AR.

A paper recently published by eLife on forebrain cortical synaptic plasticity reports that retinoic acid (RA) alters synaptopodin-dependent metaplasticity in mouse dentate granule cells (Lenz et al., 2021). RA is the active form of vitamin A that functions as a ligand for nuclear RA receptors that directly bind genomic control regions to regulate gene expression (Chambon, 1996; Ghyselinck and Duester, 2019). However, some studies have suggested that RA may have nongenomic effects outside of the nucleus, particularly with regard to synaptic plasticity (Aoto et al., 2008; Zhang et al., 2018). The current results reported by Lenz et al. demonstrate that treatment with pharmacological levels of RA can alter synaptic plasticity which may be useful to treat neurological diseases (Lenz et al., 2021). However, the results reported here and those reported by others have not shown that endogenous RA is normally required for synaptic plasticity (or any other nongenomic effect) as there are no reports of genetic loss-of-function studies that remove endogenous RA in adult brain. The implication is that pharmacological levels of RA result in nongenomic effects, some of which may be helpful to treat certain diseases but in other cases this may cause unwanted side-effects.

In recent years, many molecular and environmental factors have been studied to understand how synaptic plasticity is modulated. Sleep, as an evolutionary conserved biological function, has shown to be a critical player for the consolidation and filtering of synaptic circuitry underlying memory traces. Although sleep disturbances do not alter normal memory consolidation, they may reflect fundamental circuit malfunctions that can play a significant role in exacerbating diseases, such as autism and Alzheimer’s disease. Very recently, scientists sought to answer part of this enigma and they identified p75 neurotrophic receptor (p75NTR) as a critical player in mediating impairments in hippocampal-dependent associative plasticity upon sleep deprivation. This paper will review the role of the p75NTR, critically discuss the impact and implications of this research as the bridge for sleep research and neurological diseases.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

Objective: It was aimed to investigate the cerebral vascular territories in stroke patients with NVAF as an etiologic factor. Material and Methods: A total of 104 patients who were referred to our hospital between January 2015 and September 2016, who were over 55 years of age, identified or documented as having a standard ECG or Holter ECG record on their medical history, and diagnosed with stroke were included. Our study was designed as a retrospective analysis of prospective data. Detailed history, physical examination and electrocardiography (ECG) evaluations of the patients were performed. Descriptive statistics were used in the detection of findings, and t-test, Pearson-square test and Fisher's exact test were used for differences analysis. Results: 53.8% (N = 56) of the patients were male and 46.2% (N = 48) were female. The mean age was 73.5. MCA was the most common site of vascular involvement in NVAF-dependent strokes. In MCA vascular territory, ischemic infarcts were detected most frequently in the upper and lower divisions. SCA and PCA followed MCA. Approximately 64% of the NVAF-related strokes were anterior circulation infarction (ASE) and 22% were posterior circulation infarct (PSE). There was a significant difference in age and past stroke history factors in favor of ASE (p<0.05). There was no significant difference between ASE and PSE in HT, cardiac history and DM factors (p>0.05). Conclusion: It was emphasized that the area of the vessel that underwent ischemia in the acutely displayed infarcts and the etiological factor for this vessel area could be predicted

Polarimetric Synthetic Aperture Radar (PolSAR) images with dual polarization modes have great potential to map FSV by excellent penetration capabilities and distinct microwave scattering processes. However, the response of these SAR data to FSV is still uncertain at non-growing season. To further interpret the response of forest FSV to these dual-polarization SAR images, three types of dual polarization SAR images (GF-3, Sentinel-1, and ALOS-2) were initially acquired in coniferous planted forest at non-growing season. Then, sensitivity between FSV and all alternative features extracted from each type of SAR images were analyzed to express the difference of bands and polarization modes in deciduous (Larch) and evergreen (Chinese pine) forests. Finally, mapped FSVs using single and combined dual polarization images were derived by optimal feature sets and four machine learning models, respectively. The combined effects were also analyzed to clarify the response of FSV to dual polarization SAR images with bands and polarization modes at non-growing season. The results demonstrated that the difference of backscattering energy from different sensors is significant in Chinese pine forests, and the difference is gradually reduced in Larch forests. it is also implied that polarization mode is more important than penetration capability in mapping forest FSV in deciduous forest at non-growing season. By comparing the accuracy of mapped FSV using single and combined images, combined images have more capability to improve the accuracy and reliability of mapped FSV. Meanwhile, it is also confirmed that compensation effect with bands and polarization modes not only have great potential to delay the saturation phenomenon, but also have capability to reduce errors caused by over-estimation.

We derive time evolution equations, namely the Schrodinger-like equations and the Klein-Gordon equations for coherent fields and the Kadanoff-Baym (KB) equations for quantum fluctuations, in Quantum Electrodynamics (QED) with electric dipoles in 2 + 1 dimensions. Next we introduce a kinetic entropy current based on the KB equations in the 1st order of the gradient expansion. We show the H-theorem for the Leading-Order self-energy in the coupling expansion (the Hartree-Fock approximation). We show a conserved energy in the spatially homogeneous systems in the time evolution. We derive aspects of the super-radiance and the equilibration in our single Lagrangian. Our analysis can be applied to Quantum Brain Dynamics, that is QED with water electric dipoles. The total energy consumption to maintain super-radiant states in microtubules seems to be within the energy consumption to maintain the ordered systems in a brain.

Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

During the COVID-19 pandemic, the circulation of non–SARS-CoV-2 respiratory viruses changed throughout the world. This study aimed to analyze the effect of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (RV), and parainfluenza (PIV)-3 single infection, dual co-infection, and viral load on cytokine and chemokine expression in 300 Mexican patients with ARIs negative for SARS-CoV-2. Molecular detection and viral load were performed by RT-qPCR. Cytokine and chemokine expression was determined in samples positive for single RSV, MPV, RV, or PIV-3 infection, and in the most frequent dual co-infections, by a cytokine panel using a magnetic-bead-based multiplex immunoassay. Of the patients positive for viral infection, 91.7% had a single infection and 8.3% had dual co-infections. In this study, RSV was the respiratory virus with the highest prevalence, and the most common dual co-infection was RV+RSV. On the other hand, RV infections had the highest viral loads compared to the other viruses detected. FGF basic, MIP-1α IL-8, IP-10, MCP-1, IFN-γ, and RANTES showed differential expression between single infections and dual co-infections compared to healthy patients. We report, for the first time, the circulation of non-SARS-CoV-2 viruses in the south of Mexico and the cytokine and chemokine profiles associated with these viruses.

The connection of two phenomena - non-conservative friction forces and dissipation-induced instability can lead to many interesting engineering problems. The paper studies general material-dependent damping influence on dynamical instability of disc brake systems leading to brake squeal. The effect of general damping is demonstrated on a minimal and complex model of a disc brake. A complex system including material-dependent damping is defined in the commercial finite element software. The finite element model validated by experimental data on the brake-disc test bench is used to compute the influence of a pad and a disc damping variations on system stability by complex eigenvalue analysis. Analyzes show a significant sensitivity of the experimentally verified unstable mode of the system to the ratio of the damping between the disc and the friction material components.

The purpose of this work was to evaluate a novel methodology developed by Digital Blood Corporation (DBC) to calculate critical blood values using four non-invasive measured values as input. The values obtained using a point-of-care testing (POCT) device were utilized for comparison and reference. Radial arterial blood was collected for the POCT comparator analysis using the Abbott i-STAT^® device. The non-invasive methodology from DBC requires four parameters to be directly measured: temperature, hemoglobin, pO2, and pCO2. Subsequently, sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation are calculated using an algorithm. The agreement between the POCT and DBC’s methodology was analyzed using Bland-Altman difference plots. For a second data set, pO2 and pCO2 values collected with the POCT were used as input for DBC’s algorithm to test its robustness. Data from 37 healthy ambulatory individuals, mean age: 42.4 + 13 years; range: 18-64 years, were included in the primary analysis. In the case of the non-invasive gained four input values the greatest variation between POCT and DBC’s approach was observed for pO2 and consequently for algorithm values that depend upon pO2 precision. Replacing transcutaneous pO2 and pCO2 with POCT values demonstrates the principal ability of DBC’s algorithm to predict the additional 8 blood values in sufficient agreement with a standard POCT device in healthy patients. The algorithm developed by DBC appears to be robust in the case of healthy patients but does need the four measured input values with preciseness comparable to a POCT device to give reliable and clinically relevant results. The present study thus serves as a proof of concept to facilitate future study and further development of this methodology into a non-invasive device.

Traditional shipping ships abbreviated as Pelra have a different character from conventional ships. Hypothetically, the application of Safety Management System (SMS) on Pelra is influenced by technical and non-technical factors. These factors are control variables and determinants of action priorities if SMS is applied to the safety of traditional shipping, so that it has implications as a basis for formulating and developing safety policies for traditional shipping transportation in an effort to reduce the risk of accidents. This research uses Structural Equation Modeling by analyzing expert opinions. The results of the analysis show that technical and non-technical factors have a direct and interconnected effect on Pelra safety management. The dominant influences are non-technical factors of authority and responsibility of the company and crew as well as the feasibility of ship construction as technical and environmental factors..

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.

Insect behavior is coordinated mainly by smell, through the diverse odor-binding proteins (OBP) that allow them to identify and recognize their environment. Sensory information collected through smell is then analyzed and interpreted in the brain, allowing for correct insect functioning. The behavior of honey bees (Apis mellifera L.) can be affected by different pathogens, such as deformed wing virus (DWV). In particular, DWV variant A (DWV-A) is capable of altering olfactory sensitivity, reducing the gene expression of different OBPs, including those associated with nursing behavior. DWV is also capable of replicating itself in the sensory lobes of the brain, further compromising the processing of sensory information. This study evaluated the behavioral response of nurse honey bees exposed to a pheromone compound and the alterations in the gene expression of pre- and post-synaptic neuronal genes neuroxins-1 and neurogilin-1 in the bee heads and OBP proteins in antennae of nurse bees inoculated with DWV-A. The behavioral response of nurse bees exposed to the larval pheromone compounds benzyl alcohol was analyzed using a Y-tube olfactometer. The viral load, gene expression of OBP5 and OBP11 in antennae and the neuroxins-1 and neurogilin-1 in the bee heads were analyzed by qPCR. High viral loads significantly reduced the ability of 10- and 15-day-old nurse honey bees to choose the correct pheromone compound. Also, the gene expression of OBP5, OBP11, neuroxin-1 and neurogilin-1 in nurse honey bees decreased when they were highly infected with DWV-A. These results suggest that a DWV-A infection can disturb information processing and cause nurse honey bees to reduce their activity inside the hive, altering internal cohesion.

The therapeutic effects of volatile anesthetics on mental diseases, particularly schizophrenia, have gained considerable interest. Although isoflurane is a commonly used volatile anesthetic, there’s no more evidence that it could work on treating schizophrenia. Here, we discovered that inhaling isoflurane at low concentrations might reverse the behavioral phenotypes of schizophrenia caused by MK801, such as hyperlocomotion, pre-pulse inhibition impairment, and working memory loss. Isoflurane also helped recovering adult neurogenesis and synaptic plasticity impairments in the dentate gyrus (DG) induced by MK801. To better understand the mechanism, we discovered that isoflurane could reverse the reduction of parvalbumin (PV)-positive GABAergic interneuron (PVI) number and the aberration of NRG1-ErbB4 signaling in the DG; however, isoflurane could not reverse the schizophrenia-related phenotypes caused by PVI ablation, indicating that PVI are necessary for the therapeutic effect of isoflurane. Interestingly, isoflurane could reverse phenotypes caused by blocking PVIs GABA release in the DG, indicating the therapeutic impact is independent of PVI GABA release. Our research revealed that isoflurane might be used to treat schizophrenia, possibly through PVI in the DG.

Alzheimer’s disease (AD) is a genetically complex senile neurodegeneration with unknown etiology. The first gene discovered to be mutated in early-onset AD, the amyloid precursor protein (APP), has been widely assumed as a causal factor in the disease cascade due to its generation of Aβ species. APP has an evolutionarily conserved biological role and activates a signaling program with notable similarities to integrin—a cell adhesion receptor with a wide array of functions. Intriguingly, several AD genome-wide association study (GWAS) candidate genes, including the SHARPIN locus recently reported by us and others, influence signaling of the integrin pathway. Integrins are focal adhesion regulators and serve in nervous system development, synaptic plasticity, and Tau phosphorylation. These observations suggest that the function of APP probably goes beyond Aβ generation in AD. Aging—the strongest risk factor for AD—is associated with various clock-like events in cells. For instance, neurons are continuously impacted by stochastic ‘hits’ to their genomes in aging, in the forms of DNA damage, insertion-deletions, copy-number variations (CNVs) and other types of somatic mutations. DNA damage and somatic mutations can result in neoplastic changes and cancer in mitotically active cells. However, their consequences in post-mitotic cells such as aging neurons are less defined. The current hypothesis holds that the stochastic loss of DNA sequence data at random loci in aging affects longer genes by chance more frequently. As a result, the biological processes coordinated by long genes may be more vulnerable to such random aging effects. Curiously, as shown by us and others, long genes are strongly enriched for synapse- and cell adhesion-related ontologies, more than any other biological process or cellular compartment. In addition, among various cell types, neurons possess the highest levels of long gene expression and are therefore more vulnerable to such harmful effects. The long gene vulnerability hypothesis provides a simple link between aging and the genetic landscape of AD and warrants new strategies for disease modification.

Excitation-inhibition imbalance of GABAergic interneurons is predisposed to develop chronic temporal lobe epilepsy (TLE). We have previously shown that virtually every neuronal nitric oxide synthase (nNOS)-positive cell is a GABAergic inhibitory interneuron in the denate gyrus. The present study was designed to quantify the number of nNOS-containing hilar interneurons using stereology in pilocapine- and kainic acid (KA)-exposed transgenic adult mice that expressed GFP under the nNOS promoter. In addition, we studied the properties of miniature excitatory postsynaptic current (mEPSC) and paired-pulse response ratio (PPR) of evoked EPSC in nNOS interneurons using whole cell recording techniques. Results showed that there were fewer nNOS-immunoreactive interneurons of chronically epileptic animals. Importantly, patch-clamp recordings revealed reduction in mEPSC frequency, indicating diminished global excitatory input. In contrast, PPR of evoked EPSC following the granule cell layer stimulation was increased in epileptic animals suggesting reduced neurotransmitter release from granule cell input. In summary, we propose that impaired excitatory drive onto hippocampal nNOS interneurons may be implicated in the development of refractory epilepsy.

Graphene is a two-dimensional nanostructured material with intrinsic properties that show promising performance in various applications, including electronics, renewable energy, medicine, mechanical enforcement and others. This study reports a bottom-up approach for the conversion of cyclohexane into graphene nanoflakes, which were then deposited onto fiberglass using a non-thermal generator. The composite was characterized using transmission electron microscopy, which revealed the formation of stacked few-layer graphene with a partially disordered structure and a d-spacing of 0.358 nm between the layers. X-ray diffraction confirmed the observations from the TEM images. SEM images showed the agglomeration of carbonaceous material onto the fiberglass, which experienced some delamination due to the synthesis method. Raman spectroscopy indicated that the obtained graphene exhibited a predominance of defects in its structure. Additionally, Atomic Force Microscopy (AFM) analyses revealed the formation of graphene layers with varying levels of porosity.

The increasing amount of data transmitted through digital broadcasting and communication channels requires efficient transmission methods that make the most of limited resources such as frequency, time, and power. The layered division multiplexing (LDM) system, which is adopted by the Advanced Television Systems Committee (ATSC) 3.0 standard, is considered one of a solution for achieving efficient transmission. Additionally, the layered time-division multiplexing (LTDM) and time layered division multiplexing (TLDM) systems have been developed as well. These layered transmission systems, utilizing multiple physical layer pipes (PLPs), offer a wide range of services including mobile and rooftop TV. To compare the efficiencies of different layered transmission systems, the article introduces the concept of normalized channel capacity. This measure allows for a fair comparison among the systems by taking into account the specific channel capacity requirements of each service. By summing the normalized channel capacities, a method is proposed to select the most efficient transmission system among the four systems: LDM, LTDM, TLDM, and time division multiplexing (TDM). The Lagrange multiplier method is employed to find the parameters that maximize the sum of the normalized channel capacities in these systems. Through simulations conducted with the determined parameters, it is demonstrated that the LDM system exhibits the highest efficiency among the four systems.

Gastro-retentive floating microspheres were developed as a result of the recent advancements in floating delivery systems for drugs (FDDS), which included the uniform dispersion of multiparticulate dosage forms along the GIT. This could lead to more consistent drug absorption and a lower risk of local irritation. Microballoons (MB), a multi-unit extended release with a sphere-shaped cavity encased in a tough polymer shell, have been developed as a dosage form with exceptional buoyancy in the stomach. This preparation for constrained intestinal absorption is made to float on top of gastric acid, that has a relative density lower than 1.By using enteric acrylic polymers and the emulsion solvent diffusion method, microballoons are prepared and filled to drug in one‘s outer polymer casings. Enteric acrylic plastics are used to generate microballoons that are drug-loaded in one‘s external polymer casings and dissipate in a solution of dichloromethane and ethanol. Cavity development in microparticles seems to be particularly correlated with dichloromethane evaporation. Microballoons with a drug distributed or dispersed all through the particle-matrix have the potential for a controlled drug release and float continuously for more than 12 hours in vitro out over the surface of an acidified dissolution medium with surfactant. The drug is released slowly and at the desired rate as the microballoons glide over the components of the stomach, increasing gastro-retention time and lowering fluctuations in plasma concentration.

To explore the impact of parenting styles on the perception of campus non-physical bullying, 492 students in upper elementary school grades were surveyed by using the Delaware Bullying Victimization Scale, the Negative Coping Style Scale, the Negative Affect Scale, and the Egna Minnen Beträffende Uppfostran Questionnaire. The questionnaire survey was conducted in the fifth and sixth grades of eight primary schools in Zhejiang province. The results showed that cyberbullying was not significantly related to an anxious parenting style, but negative affect experiences, negative coping styles, negative family parenting styles, and the perception of campus non-physical bullying were all positively correlated with each other (p < 0.05). The refusal parenting style was shown to be an important factor that affected students’ perception of campus non-physical bullying; it was observed to directly affect students’ perception of campus non-physical bullying and indirectly affect students’ perception of campus non-physical bullying by influencing negative affect experiences and negative coping styles. In conclusion, negative affect experiences and negative coping styles had a chain-like mediating effect between the refusal parenting style and students’ perception of campus verbal bullying. Moreover, negative affect experiences had a partial mediating effect between the refusal parenting style and students’ perceptions of campus cyberbullying, relationship bullying, and non-physical bullying total scores. Implications and suggestions based on these results are also discussed.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Major depressive disorder (MDD) is a common mental disorder, which results in seriously impaired condition in the patients and great global disability burden. In light of its quite diverse etiologies, comorbidity with many other diseases, and complex underlying pathology, it has been a great challenge to understand the physiological basis of MDD, which may be a complex of related diseases, rather than a single one. In addition to the partial understanding of MDD, the individual heterogeneities among patients may render the development of a universal treatment an elusive goal. But studying how each of currently available treatments affects the disease can generate useful information to stratify patients into different subtypes for individualized treatments. In this case report, we present the first report of repeated success of using meditation as the only treatment of MDD, compared to initial success but no remission with other conventional antidepressants on the same patient. We hypothesized that the short but continuous natural pain during one-hour meditation sittings has the therapeutic effect to treat depression in the case of this patient and potentially others with MDD. This special opportunity of eliminating tremendous heterogeneity among different individuals has enabled us to probe deeply into the potential mechanism of depression treatments and the complex physiology of depression itself, both of which have likely profound implications in the treatment of other MDD patients as well. More importantly, this case report helps us dissect one specific component of meditation for its long-known and well-established benefit against depression.

Malnutrition problems are related to diets that lack one or more essential elements, which it is extremely important to food enrichment to improve the content of compounds effective for health. The objective of this study is to evaluate the effect of the addition of Ca2+, K+ and Mg2+ on the induction of nutraceutical quality in grafted tomatoes grown in the NFT (Nutrient Film Technique) system. In the experiment, two factors were evaluated: plants with and without grafting and the foliar application of 10 ml L−1 Ca2+, 4 ml L−1 K+ and 10 ml L−1 Mg2+ cations separately for each case, in addition to the control. The treatments were evaluated using a completely randomized design, with 5 repetitions per treatment. The interactive effects between grafting and foliar application of Ca2+ induced a greater content lycopene, β-carotene and total flavonoids in fruits of tomato. The interactive effects between the graft and the Mg2+ foliar applications obtained the best results in the phenol content. As regards, capacity DPPH and ABTS, the graft decreased concentration, increasing the content of these through foliar applications of calcium. Regarding the enzymatic variables, graft factor increased activity catalase, glutathione peroxidase and phenylalanine ammonium lyase, obtained the best results graft interaction and foliar application of calcium and magnesium. The results obtained demonstrate the influence of the use of grafts and foliar applications of cal-cium and magnesium as tools that could improve the nutraceutical quality content of tomato crop

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in broader range of patients. Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g. documented history of HF, left ventricular ejection fraction ≤40%, or BNP levels ≥100 pg/mL). Participants, aged 61±10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. Results: Lower baseline BNP correlated with reduced AFEQT scores. Post-CA, all groups showed significant AFEQT score improvements. Lower BNP group displayed notable enhancements (18.2±1.2, 15.0±1.1, 12.6±1.2, 13.6±1.2, p<0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/ml) exhibited significant QOL improvements. Comparing PAF and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. Conclusion: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvement.

Abstract: Background: Non-invasive acquistion of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r=0.64) and PCS (r=0.55) (p<0.01), as well as MAPIBP/DBPIBP for PES (r=0.6/0.55) and PCS (r=0.5/0.45) (p<0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease(0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

We present an any-to-one voice conversion (VC) system, using an autoregressive model and LPCNet vocoder, aimed to enhance the converted speech in terms of naturalness, intelligibility, and speaker similarity. As the name implies, non-parallel any-to-one voice conversion does not require paired source and target speeches and can be employed for arbitrary speech conversion tasks. Recent advancements in neural-based vocoders, such as WaveNet, have improved the efficiency of speech synthesis. However, in practice, we find that the trajectory of some generated waveforms is not consistently smooth, leading to occasional voice errors. To address this issue, we propose to use an autoregressive (AR) conversion model along with the high-fidelity LPCNet vocoder. This combination not only solves the problems of waveform fluidity but also produces more natural and clear speech, with the added capability of real-time speech generation. To precisely represent the linguistic content of a given utterance, we use speaker-independent PPG features (SI-PPG) computed from an automatic speech recognition (ASR) model trained on a multi-speaker corpus. Next, a conversion model maps the SI-PPG to the acoustic representations used as input features for the LPCNet. The proposed autoregressive structure enables our system to produce the following prediction step outputs from the acoustic features predicted in the previous step. We evaluate the effectiveness of our system by performing any-to-one conversion pairs between native English speakers. Experimental results show that the proposed method outperforms state-of-the-art systems, producing higher speech quality and greater speaker similarity.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

In food industry, there is a growing demand for cost-effective methods for inline inspection of food items able to non-invasively detect small foreign bodies which may have contaminated the product during the production process. Microwave imaging may be a valid alternative to the existing technologies, thanks to its inherently low-cost and its capability of sensing low-density contaminants. In this paper, a low-complexity microwave imaging system specifically designed to enable the inspection of a large variety of food products is presented. The system consists of two Circularly Loaded Antipodal Vivaldi Antennas, having a very large operative band, from 1 to 15 GHz, thus allowing a suitable spatial resolution for different food products from mostly fatty to high water-content ones. The antennas are arranged in such a way to collect the signal useful to exploit a recently proposed real-time microwave imaging strategy, leveraging the inherent symmetries usually characterizing food items. The system is experimentally characterized, and the achieved results compare favorably with the design specifications and the numerical simulations. Relying on these positive results, a first experimental proof of the effectiveness of the whole system is presented, which confirms its efficacy.

Water pollution, intensified by the release of hard-to-degrade pollutants, poses severe threats to ecosystems, human health, and economic development. The existing advanced oxidation processes often involve high operational costs and may result in secondary pollution, highlighting the necessity for innovative and more sustainable solutions. To address these challenges, our study introduces a cost-effective and eco-friendly corona discharge barrier plasma discharger for wastewater treatment. Through the central composite design/response surface methodology, a high decolorization rate of 98% of methylene blue (MB) within 10 minutes was achieved by optimizing parameters such as pH and voltage. Furthermore, the mechanisms of the generation of reactive oxygen species via this device was discussed in detail and the degradation pathways of MB were described. Moreover, this device is also very energy-efficient, with a low energy density and electrical energy per order of 0.15 watt/mL and 5.79 kWh/m³/order, respectively. In conclusion, the plasma discharger developed in this study provides a cost-effective and environmentally sustainable solution for dye wastewater treatment. This research contributes significantly to the advancement of sustainable dye wastewater management practices, offering an innovative method that meets both environmental and economic objectives.

Mouse models are frequently used to study Huntington’s disease (HD). Onset and severity of neuronal and behavioral pathologies vary greatly between HD mouse models, which results from different huntingtin expression levels and different CAG repeat length. HD pathology appears to depend also on strain background of mouse models. Thus, behavioral deficits of HD mice are more severe in the FVB than in the C57BL/6 background. Alterations in medium spiny neuron (MSN) morphology and function has been well documented in young YAC128 mice in the FVB background. We here tested the relevance of strain background for mutant huntingtin (mHTT) toxicity on the cellular level by investigating HD pathologies in YAC128 mice in the C57BL/6 background (YAC128/BL6). Morphology, spine density, synapse function and membrane properties were not or only subtly altered in MSNs of 12-month-old YAC128/BL6 mice. Despite the mild cellular phenotype, YAC128/BL6 mice showed deficits in motor performance. More pronounced alterations in MSN function were found in the HdhQ150 mouse model in the C57BL/6 background (HdhQ150/BL6). Consistent with the differences in HD pathology, the number of inclusion bodies was considerably lower in YAC128/BL6 mice than HdhQ150/BL6 mice. This study highlights the relevance of strain background for mHTT toxicity in HD mouse models.

One of the most commonly known chronic neurodegenerative disorders, Alzheimer’s disease (AD), manifests the common type of dementia in 60–80% of cases. From a clinical standpoint, a patent cognitive decline and a severe change in personality, as caused by a loss of neurons, is~usually evident in AD with about 50 million people affected in 2016. The disease progression in patients is distinguished by a gradual plummet in cognitive functions, eliciting symptoms such as memory loss, and eventually requiring full-time medical care. From a histopathological standpoint, the~defining characteristics are intracellular aggregations of hyper-phosphorylated tau protein, known as neurofibrillary tangles (NFT), and depositions of amyloid β-peptides (Aβ) in the brain. The~abnormal phosphorylation of tau protein is attributed to a wide gamut of neurological disorders known as tauopathies. In addition to the hyperphosphorylated tau lesions, neuroinflammatory processes could occur in a sustained manner through astro-glial activation, resulting in the disease progression. Recent findings have suggested a strong interplay between the mechanism of Tau phosphorylation, disruption of microtubules, and synaptic loss and pathology of AD. The mechanisms underlying these interactions along with their respective consequences in Tau pathology are still ill-defined. Thus, in this review: (1) we highlight the interplays existing between Tau pathology and AD; and (2) take a closer look into its role while identifying some promising therapeutic advances including state of the art imaging~techniques.

Financial system is essentially chaotic and unstable if there is not any external inputs. By means of Lyapunov function method, design of switching law, novel fuzzy assumption, $L^p$ estimation technique and Laplace semigroup theory, the author presents the boundedness and LMI-based (globally) asymptotical input-to-state stability criteria of financial systems. Particularly, the globally asymptotical stability in the meaning of switching implies that when the time $t$ is big enough, the dynamic of any subsystem must approach its unique equilibrium point. Besides, the global financial crisis often erupts periodically, which illuminates that the global stability in the classical sense is actually meaningless. So the stability in the meaning of switching proposed in this paper is suitable and appropriate. Numerical examples illuminate the effectiveness of the obtained results.

This paper reports a new global Mittag-Leffler synchronization criterion with regard to fractional-order hyper-chaotic financial systems by designing the suitable impulsive control and the state feedback controller. The significance of this impulsive synchronization lies in the fact that the backward economic system can synchronize asymptotically with the advanced economic system under the effective impulse macroeconomic management means. Matlab LMI-toolbox is utilized to deduce the feasible solution in numerical example, which shows the effectiveness of the proposed methods. It is worth mentioning that the LMI-based criterion usually requires the activation function of the system to be Lipschitz, but the activation function in this paper is fixed and truly nonlinear, which cannot be assumed to be Lipschitz continuous. This is another mathematical difficulty overcome in this paper.

One of the non-linear phenomena that affect high bandwidth and long reach communication systems is the non-linear phenomenon called four-wave mixing (FWM). Unfortunately, the simulation of such systems aiming to obtain their design parameter limitations require more time as the number of channels increases. In this paper, we propose a new high-performance computational model to obtain optimal design parameters in a multi san Dense Wavelength Division Multiplexing (DWDM) system, limited by FWM and the intrinsic Amplified Spontaneous Emission (ASE) noise of optical amplifiers employed in each segment. The simulation in this work provides a complete optical design characterization and compares the efficiency and speed improvement of the proposed parallelization model versus a previous sequential model. Additionally, an analysis of the computational complexity of parallel model is presented, where two parallel implementations are used. First, Open Multi−Processing (OpenMP), based on the use of a central, multi-core processing unit is used and secondly the Compute Unified Device Arquitecture (CUDA), which is based on the use of graphics processing unit. Results show that parallelism improves to up to 40 times the performance of the simulation when nested parallelization with CUDA is used, over de sequential method and up to 6 times compared with the implementation with OpenMP using 12 processors. Within our parallel implementation, it is possible to simulate with an increased number of channels, that was unpractical in the sequential simulation.

Corresponding to the principles of biological synapses, an essential prerequisite for hardware neural networks using electronics devices is continuous regulation of conductance. We implemented artificial synaptic characteristics in a (GeTe/Sb2Te3)16 iPCM with a superlattice structure under optimized identical pulse trains. Based on atomically controlling the Ge switch in the phase transition that appears in the GeTe/Sb2Te3 superlattice structure, multiple conductance states were implemented by applying the appropriate electrical pulses. Furthermore, we found that the bidirectional switching behavior of a (GeTe/Sb2Te3)16 iPCM can achieve a desired resistance level using the pulse width. Therefore, we also fabricated a Ge2Sb2Te5 PCM and designed a pulse scheme based on the phase transition mechanism to compare to the (GeTe/Sb2Te3)16 iPCM. We designed an identical pulse scheme that implements linear and symmetrical LTP and LTD based on the iPCM mechanism. As a result, the (GeTe/Sb2Te3)16 iPCM showed relatively excellent synaptic characteristics by implementing gradual conductance modulation, a nonlinearity value of 0.32, and LTP/LTD 40 conductance states using identical pulses trains. Our results demonstrate the general applicability of the artificial synaptic device for potential use in neuro-inspired computing and next generation non-volatile memory.

Complex diseases such as cancer are caused by changes in the Gene Regulatory Networks. Systems that model the complex dynamics of these networks along with adapting to real gene expression data are closer to reality and can help understand the creation and treatment of cancer. In this paper, for the first time, modelling of gene regulatory networks is performed using delayed nonlinear variable order fractional systems in the state space by a new tool called GENAVOS. This tool uses gene expression time series data to identify and optimize system parameters. This software has several tools for analyzing system dynamics. The results show that the nonlinear variable order fractional systems have very good flexibility in adapting to real data. We found that regulatory networks in cancer cells actually have a larger delay parameter than in normal cells. It is also possible to create chaos, periodic and quasi-periodic oscillations by changing the delay, degradation and synthesis rates. Our findings indicate a profound effect of time-varying order on these networks, which may be related to a type of cellular memory due to epigenetic and environmental factors. We showed that by changing the delay parameter and the variable order function for a normal cell system, its behavior changes and becomes quite similar to the behavior of a cancer cell. This work also confirms the effective role of the miR-17-92 cluster in the cancer cell cycle. GENAVOS is available at https://github.com/hanif-y/GENAVOS with its user guide and MATLAB codes.

Both brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) have multiple roles in the various aspects of neurons, including cell survival and synaptic function. BDNF and its receptor TrkB express in the central nervous system (CNS) neurons extensively, and contribution of BDNF/TrkB system in neuronal function is evident, thus, its downregulation has been considered to be involved in the pathogenesis of Alzheimer’s disease (AD). GCs, a stress-related molecule, and glucocorticoid receptor (GR) are also considered to be associated with AD, in addition to mental disorders such as depression. Importantly, a growing body of evidence suggest a close relationship between BDNF/TrkB-mediated signaling and GCs/GR system in the CNS. Here, we introduce current studies on the interaction among neurotrophic system and stress in CNS neurons, and discuss their involvement in the pathophysiology of AD.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

Analysing and understanding donor behaviour in Non-profit Organisations (NPOs) is challenging due to the lack of human and technical resources. Machine learning (ML) techniques can analyse and understand donor behaviour at a certain level; however, it remains to be seen how to build and design an Artificial Intelligence enabled Decision Support System (AI-enabled DSS) to analyse donor behaviour. Thus, this paper proposes an AI-enabled DSS conceptual design to analyse donor behaviour in NPOs. A conceptual design is created following a Design Science Research approach to evaluate an AI-enabled DSS's initial DPs and features to analyse donor behaviour in NPOs. The evaluation process of the conceptual design applied formative assessment through conducting interviews with stakeholders from NPOs. The interviews were conducted using the Appreciative Inquiry framework to facilitate the process of interviews. The results of analysis based on the interviews provide insightful information not only about the proposed conceptual design for an AI-enabled DSS, but also about what is required to analyse donor behaviour NPOs using DSS. Evaluating the conceptual design results recommend efficiency, effectiveness, flexibility, and useability in the requirements of the AI-enabled DSS. This research contributes to the design knowledge base of AI-enabled DSS for analysing donor behaviour in NPOs. Future research will combine theoretical components to introduce a practical AI-enabled DSS for analysing donor behaviour in NPOs. This research is limited to such analysis on donors who donate money or volunteer time for NPOs.

Abstract Although we know something about single cell neuromuscular junction, It is still mysterious how multiple skeletal muscle cells coordinate to complete the intricate spatial curve movement. Here I propose a hypothesis that skeletal muscle cell populations with action potentials are alligned according to a curved manifolds on space(a curved shape on space) and the skeletal muscle also moves according to this corresponding shape(manifolds) when an specific motor nerve impulses are transmitted. the action potential of motor nerve fibers has the characteristics of time curve manifold and this time manifold curve of motor nerve fibers come from visual cortex in which a spatial geometric manifolds are formed within the synaptic connection of neurons. This spatial geometric manifolds of the synaptic connection of neurons orginate from spatial geometric manifolds in outside nature that are transmitted to brain through the cone cells and ganglion cells of the retina.Further,the essence of life is that life is an object that can move autonomously and the essence of life's autonomous movement is the movement of proteins. theoretically, due to the infinite diversity of geometric manifold shapes in nature, the arrangement and combination of 20 amino acids should have infinite diversity, and the geometric manifold formed by protein three-dimensional spatial structure should also have infinite diversity.

Cooperative non-orthogonal multi access communication is a promising paradigm for the future wireless networks because of its advantages in terms of energy efficiency, wider coverage and interference mitigating. In this paper, we study the secrecy performance of a downlink cooperative non-orthogonal multi access (NOMA) communication system under the presence of an eavesdropper node. Smart node selection based on feed forward neural networks (FFNN) is proposed in order to improve the physical layer security (PLS) of a cooperative NOMA network. The selected cooperative relay node is employed to enhance the channel capacity of the legal users, where the selected cooperative jammer is employed to degrade the capacity of the wiretapped channel. Simulations of the secrecy performance metric namely the secrecy capacity ($C_S$) are presented and compared with the conventional technique based on fuzzy logic node selection technique. Based on our simulations and discussions the proposed technique outperforms the existing technique in term the of secrecy performance.

Objective: To investigate whether impaired plantar cutaneous vibration perception contributes to axial motor symptoms in Parkinson’s disease (PD) and whether anti-parkinsonian medication and subthalamic nucleus deep brain stimulation (STN-DBS), show different effects. Methods: Three groups were tested: PD patients on medication (PD-MED), PD patients on medication and additional STN-DBS (PD-MED–DBS), and healthy subjects (HS) as reference. Motor performance was analyzed using a pressure distribution platform. Plantar cutaneous vibration perception thresholds (VPT) were investigated using a customized vibration exciter at 30 Hz. Results: Motor performance of PD-MED and PD-MED–DBS was characterized by greater postural sway, smaller limits of stability ranges, and slower gait, due to shorter strides, fewer steps per minute, and broader stride widths compared to HS. Comparing patient groups, PD-MED–DBS showed better overall motor performance than PD-MED, particularly for the functional limits of stability and gait. VPTs were significantly higher for PD-MED compared to HS, which suggests impaired plantar cutaneous vibration perception in PD. However, PD-MED–DBS showed less impaired cutaneous vibration perception than PD-MED. Conclusion: PD patients suffer from poor motor performance compared to healthy subjects. Anti-parkinsonian medication in conjunction with STN-DBS seems to be superior for normalizing axial motor symptoms compared to medication alone. Plantar cutaneous vibration perception is impaired in PD patients, whereas anti-parkinsonian medication together with STN-DBS is superior for normalizing tactile cutaneous perception compared to medication alone. Consequently, based on our results and the findings of the literature impaired plantar cutaneous vibration perception might contribute to axial motor symptoms in PD.

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence development of both ASD and PD with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.

Reporting on CSR activities has become the essence of reporting for modern business entities. In this regard, particular attention is paid to public interest companies. Therefore, the following paper aims to answer the question of whether there are differences in the linguistic structure of the studied CSR reports in three selected industry indices on the Warsaw Stock Exchange (WSE) in Poland, i.e. WIG-energy index, WIG-fuel index, WIG-mining index and their relationship with the performance of selected companies. The study was conducted on a purposely selected sample of companies between 2013 and 2018. A total of 138 CSR reports and 138 annual separate financial statements prepared in accordance with international balance sheet law were collected. The study was carried out based on a panel regression model. It was found that CSR reports contained similar average percentages of parts of speech such as nouns and adjectives. When linking the economic performance of companies, expressed with selected indices, to the information on the implementation of CSR concepts, it was revealed that the results are more likely to describe business performance when it is satisfactory.

In previous work, a quantum mathematical formalism associated an element of experience with a single sensory neuron, as a local reduction of a global mental state. In contrast to the binary objective states of neuronal polarisation/depolarisation, neuronal experience was modeled as a continuous variable, the instantaneous value of which could only be estimated statistically from an ensemble of evoked responses to stereotyped stimulus presentation. In the present work, the quantum operations formalism of energy dissipation through amplitude damping is adopted to explain how smooth evolution of conscious experience might arise from discrete spikes and discontinuous synaptic transmission between neurons.

In a single-center, retrospective study, 22 cases were enrolled and divided into two groups: those who underwent surgical wide excision (group A) and those who did not (group B). The study included 13 cases in group A and 9 cases in group B. In group A, 6 cases solely underwent surgical wide excision, while 7 cases received additional treatments like radiotherapy or chemotherapy. Conversely, in group B, 4 cases received chemotherapy, 4 cases received radiotherapy, and 1 case was managed through observation alone. The mean follow-up time was 60.15 months in group A and 43.44 months in group B, with no significant difference observed. In group A, 9 cases resulted in mortality, whereas 6 cases died within the follow-up period in group B. Lesion-free intervals post-operation were observed predominantly in group A, while 7 cases in group B never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Among non-HIV Kaposi’s sarcoma patients, surgical wide excision appears to have a role in treatment. Patients in group A exhibit a more favorable outcome in the survival curve analysis.

Dendritic spines are essential for synaptic function because they constitute the neurons' postsynaptic compartment that receives the most excitatory input. The extracellularly shorter variant of the presynaptic cell adhesion molecules neurexins, β-neurexins, has been implicated in various aspects of synapse function including neurotransmitter release. However, its role in developing or stabilizing dendritic spines as fundamental computational units of excitatory synapses remained unclear. Here, we show by morphological analysis that the deletion of β-neurexins in hippocampal neurons in vitro and in hippocampal tissue in vivo affects presynaptic dense-core vesicles and, unexpectedly, postsynaptic spine structure. Specifically, we observed that the absence of β-neurexins led to an increase in longer spinous protrusions in vitro and more mature mushroom-type spines in the CA1 region of adult knockout mice. In addition, deletion of β-neurexins caused alterations in spine head dimension and more spines with perforations of their postsynaptic density but no change in the overall number of spines or synapses. Our results indicate that presynaptic β-neurexins play a role across the synaptic cleft, possibly by aligning with postsynaptic binding partners and glutamate receptors via transsynaptic columns.

Protons are gaining increasing attention as neurotransmitters due to their extraordinary abilities to rapidly transfer electrical charge, mobilize cellular calcium and modulate ion channels. How all this is possible is currently the subject of in-depth studies and discussions concerning not only neurophysiology, but also biological materials for artificial intelligence. In this short review, some biochemical mechanisms are described by which protons, in combination with calcium, can initiate firing in sensory neurons and transmit impulse across synapses. Furthermore, mechanisms are put forward concerning how three neurotransmitters, glutamate, gamma-aminobutyric acid and acetylcholine, are able to generate protons. The results of the numerous experimental works taken into consideration indicate that protons can play a fundamental role both in the generation and in the transmission of the nerve impulse.

Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, a group of proteins with roles in neuronal ion channel regulation and synaptic transmission. We have previously demonstrated that a male Fgf14-/- mouse model recapitulates salient endophenotypes of synaptic dysfunction and behaviors associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14-/- model provides a valuable tool to interrogate pathways that might be related to the disease mechanism. Here, we performed label free quantitative proteomics and bioinformatics to identify enriched pathways at the proteome level in the male and female hippocampi from Fgf14+/+ and Fgf14-/- mice. We discovered that many differentially expressed proteins in Fgf14-/- animals are associated with SZ. In addition, measured changes in the proteome and signaling pathways were predominantly sex-specific with the male Fgf14-/- being distinctly enriched for pathways associated with neuropsychiatric disorders and addiction and the female exhibiting modest changes. In the male Fgf14-/- mouse the major protein changes that could in part explain the previously described neurotransmission and behavioral phenotype of this model were loss of ALDH1A1 and PRKAR2B. ALDH1A1 has been shown to mediate an alternative pathway for GABA synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14-/- mouse as a useful preclinical model of SZ for generating hypothesis on the disease mechanism, sex-specific manifestation and therapy.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p&lt;0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research, and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models are essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models as well as in patients with Alzheimer’s disease, These tools have facilitated our understanding of disease mechanisms, and provided longitudinal monitoring of treatment effect in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes, and discuss outstanding challenges in disease animal models and future outlook in on-chip characterization of imaging biomarkers towards clinical translation.

For the treatment of cancer and other diseases, therapeutic targeting of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) is an attractive approach. RNA-based therapeutics have been extensively researched over the past decade, with antisense oligonucleotides and small interfering RNAs being the most commonly used. Some of these have even gained FDA approval. However, the results of trials have been mixed, with some studies reporting strong effects while others have shown limited effectiveness or toxicity. Alternative treatments, such as antimiRNAs, are currently in clinical trials. There is growing interest in the use of lncRNA-based therapies. This Perspective discusses the main challenges of ncRNA therapeutics, including specificity, delivery and tolerability. It also highlights emerging approaches that aim to improve their success.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Non-compliant (NC) structures are often encountered in building construction in developing countries. This is a condition whereby erected buildings do not follow regulatory standards, especially in the provision of reinforcements. Therefore, under an earthquake load, the structures do not have sufficient resistance against such load. The structural elements of the building, which often have NC conditions, are the beam-column joints because they do not contain adequate shear reinforcements due to installation difficulty. This study aims to determine the structural performance of the reinforced concrete (RC) frame, which has a reinforcement deficiency in the beam-column joints. Numerical simulation was conducted on the Kakaletsis structure model by modifying the reinforcement details at the joints to represent the NC conditions. The non-linear modeling and analysis of the structural model were carried out using ATENA software. The analysis showed that the reduction in shear reinforcements in the NC model joint caused a decrease in load-carrying capacity by about 26.04%. A shift was also observed in the collapse pattern, i.e., from the beam to the end of the column, causing global failure and reducing the undamaged but increasing more severely damaged condition. This showed that the NC structure, due to the non-conformance of reinforcement, significantly reduced the structure's performance.

An exhaustive list of thirteen instances of reports confirming experimentally the relativistic Doppler relation, are examined. For those involving longitudinal Doppler, the non-relativistic relation is seen to be confirmed, within the reported experimental accuracies, to the same degree as the standard relativistic relation. Higher values of the speed of the emitter would be required to examine further the claimed confirmations. For those reports involving saturation spectroscopy, there is much confusion over the appropriate Doppler relation to be used, together with some serious analytical flaws. For the two cases that involve transverse Doppler, there are seen to be either serious faults in the theoretical part, or intrusion from the first order effect. Therefore, the reported conclusions - that the results for the experiments confirm the relativistic SR relation - cannot be justified by any of the experimental works.

We introduce a novel key exchange protocol based on non-commutative matrix multiplication defined in $\mathbb{F}_p^{n \times n}$. The security of our method does not rely on computational problems as integer factorization or discrete logarithm whose difficulty is conjectured. We show that the public, secret and channel keys become indistinguishable to the eavesdropper under matrix multiplication. Remarkably, for achieving a 512-bit security level, the public key is 1024 bits and the private key is 768 bits, making them the smallest keys among post-quantum key exchange algorithms. Also, we discuss how to achieve key authentication, interdomain certification and Perfect Forward Secrecy (PFS). Therefore, Lizama's algorithm becomes a promising candidate to establish shared keys and secret communication between (IoT) devices in the quantum era.

We introduce a novel key exchange protocol based on non-commutative matrix multiplication defined in $\mathbb{Z}_p^{n \times n}$. The security of our method does not rely on computational problems as integer factorization or discrete logarithm whose difficulty is conjectured. We claim that the unique eavesdropper's opportunity to get the secret/private key is by means of an exhaustive search which is equivalent to the unsorted database search problem. Furthermore, we show that the secret/private keys become indistinguishable to the eavesdropper. Remarkably, to achieve a 512-bit security level, the keys (public/private) are of the same size when matrix multiplication is done over a reduced 8-bit size modulo. Also, we discuss how to achieve key certification and Perfect Forward Secrecy (PFS). Therefore, Lizama's algorithm becomes a promising candidate to establish shared keys and secret communication between (IoT) devices in the quantum era.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying \begin{align*} \left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2, \quad \forall \lambda_j \in \mathbb{K}, 1\leq j \leq n, \forall n \in \mathbb{N}. \end{align*} For $d\in \mathbb{N}$, let $\mathbb{K}^d$ be the standard $d$-dimensional non-Archimedean Hilbert space. Let $m \in \mathbb{N}$ and $\text{Sym}^m(\mathbb{K}^d)$ be the non-Archimedean Hilbert space of symmetric m-tensors. We prove the following result. If $\{\tau_j\}_{j=1}^n$ is a collection in $\mathbb{K}^d$ satisfying $\langle \tau_j, \tau_j\rangle =1$ for all $1\leq j \leq n$ and the operator $\text{Sym}^m(\mathbb{K}^d)\ni x \mapsto \sum_{j=1}^n\langle x, \tau_j^{\otimes m}\rangle \tau_j^{\otimes m} \in \text{Sym}^m(\mathbb{K}^d)$ is diagonalizable, then \begin{align}\label{WELCHNONABSTRACT} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |\langle \tau_j, \tau_k\rangle|^{2m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{WELCHNONABSTRACT}) as the non-Archimedean version of Welch bounds obtained by Welch [\textit{IEEE Transactions on Information Theory, 1974}]. We formulate non-Archimedean Zauner conjecture.

Nonionizing millimeter-waves (MMW) interact with cells in a variety of ways. Here the inhibited cell division effect was investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm2 safety standards. Irradiation using a power density of about 1.0 mW/cm2 , SAR over 5-6 hours on 50 cells/μl samples of Saccharomyces cerevisiae model organism resulted in 62% growth rate reduction compared to the control (sham). The effect was specific for 85-105 GHz range, and was energy and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deleted cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause permanent genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm2) and compared to that of a compact waveguide (17.17 mW/cm2) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. We have shown that non-thermal MMW radiation has potential for future use in treatment of yeast related diseases and other targeted biomedical outcomes.

Nonionizing millimeter-waves (MMW) are reported to interact with cells in a variety of ways. Possible mechanisms of the inhibited cell division effect were investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm² safety standards. ~1.0 mW/cm² exposure over 5-6 hours treatment on 50 cells/μl samples of Saccharomyces cerevisiae model organism, resulted in 62% growth rate reduction compared to control (sham). The effect was specific for 85-105 GHz range and energy dose and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deletion cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm²) and compared to that of a compact waveguide (17.17 mW/cm²) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. Combinations of MMW mediated Structure Resonant Energy Transfer (SRET), membrane modulations eliciting signaling effects, and energetic resonance with biomolecules were indicated to be responsible for the observations reported. Our results provide novel mechanistic insights enabling innovative applications of nonionizing radiation procedures for eliciting targeted biomedical outcomes.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Wine is a processed beverage that offers high nutritional and health benefits. It is produced from grape must, which undergoes fermentation by yeasts (and sometimes lactic acid bacteria) to create a product that is highly appreciated by consumers worldwide. However, if only one type of yeast, specifically Saccharomyces cerevisiae, were used in the fermentation process, the resulting wine would lack aroma and flavor and may be rejected by consumers. To produce wine with a desirable taste and aroma, non-Saccharomyces yeasts are necessary. These yeasts contribute volatile aromatic compounds that significantly impact the wine’s final taste. They promote the release of primary aromatic compounds through a sequential hydrolysis mechanism involving several glycosidases unique to these yeasts. This review will discuss the unique characteristics of these yeasts (Schizosaccharomyces pombe, Pichia kluyveri, Torulaspora delbrueckii, Wickerhamomyces anomalus, Metschnikowia pulcherrima, Hanseniaspora vineae, Lachancea thermotolerans, Candida stellata, and others) and their impact on wine fermentations and co-fermentations. Their existence and the metabolites they produce enhance the complexity of wine flavor, resulting in a more enjoyable drinking experience.

Post-quantum public cryptosystems introduced so far do not define an scalable public key infrastructure for the quantum era. We demonstrate here a public certification system based in Lizama’s non-invertible Key Exchange Protocol which can be used to implement a public key infrastructure (PKI), secure, scalable, interoperable and efficient. We show functionality of certificates across different certification domains. Finally, we discuss that non-invertible certificates can exhibit Perfect Forward Secrecy (PFS).

It is well established in literature that the public debt and economic growth bear positive and non-linear relationship. However, in recent literature, evidence of no causal relationship is found when accounted for endogeneity in case of advanced economies (Panizza & Presbitero, 2014). Chudik, Mohaddes, Pesaran, & Raissi, (2017) analyse the data on forty countries and find no evidence of universally applicable threshold effect in the relationship between debt and growth. These advancements in the debt-growth literature provides the motivation to re-explore the relationship between public debt and economic growth under non-linearity and endogeneity in context of developing economies of South Asia including Pakistan, India, Bangladesh and Sri-Lanka for the period 1980-2014. There exists a significant, positive but nonlinear relationship between the public debt and economic growth for the selected set of developing countries when accounted for endogeneity and non-linearity. The negative association between the public debt and economic growth for SAARC region is found when the debt level is higher than 61% of GDP which is quite lower than developed economies (90% of GDP). Individual threshold levels for debt-to-GDP ratio divulge that Sri Lanka, Pakistan and India need to control their public borrowings as their current debt levels are higher and/or around the respective threshold levels.

We establish a new Gagliardo-Nirenberg inequality characterized by radial symmetry and involving potentials exhibiting pure power polynomial behaviour. As an application of our result, we investigate the existence of extremals for this inequality, which also correspond to stationary solutions for the nonlinear Schrödinger equation with inhomogeneous nonlinearity, competing with Hs-subcritical nonlinearities, either of local or non-local nature.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

This article develops a duality principle and a related convex dual formulation suitable for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a model in non-linear elasticity.

Near-fault ground motions can cause severe damage to civil structures, including bridges. Safety assessment of these structures for near fault ground motion is usually performed through Non-Linear Dynamic Analyses, while faster methods are often used. IMPAb (Incremental Modal Pushover Analysis for Bridges) permits to investigate the seismic response of a bridge by considering the effects of higher modes, which are often relevant for bridges. In this work, IMPAb is applied to a bridge case study considering near-fault pulse-like ground motion records. The records were analyzed and selected from the European Strong Motion Database and the pulse parameters were evaluated. In the paper results from standard pushover procedures and IMPAb are compared with nonlinear Response-History Analysis (NRHA), considering also the vertical component of the motion, as benchmark solutions and incremental dynamic analysis (IDA). Results from the case study demonstrate that the vertical seismic action has a minor influence on the structural response of the bridge. Therefore IMPAb, which can be applied considering vertical motion, remains very effective conserving the original formulation of the procedure, and can be considered a well performing procedure also for near-fault events.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Turbulent dissipation is a central issue in the star and galaxy formation process. Its fundamental property of space-time intermittency, well characterised in incompressible laboratory experiments, remains elusive in cosmic turbulence. Progress requires the combination of state-of-the-art modelling, numerical simulations and observations. The power of such a combination is illustrated here where the statistical method intended to locate extrema of velocity shears in a turbulent field is applied to numerical simulations of compressible magneto-hydrodynamical (MHD) turbulence dedicated to dissipation scales and to a nearby turbulent diffuse molecular cloud. We demonstrate that short-spacing increments of observables can detect strongly dissipative structures. In our simulations, we compute structure functions of various synthetic observables and show that they verify Extended Self-Similarity. This allows to compute their intermittency exponents and we show how they could help constraining some properties of the underlying three-dimensional turbulence. In observations of a turbulent cloud close to the Sun in our Galaxy, a remarkable coherent structure of velocity shear extremum is disclosed . At the location of the largest velocity shear, this coherent structure is found to foster 10 × more carbon monoxide molecules than standard diffuse molecular gas, an enrichment supported by models of non-equilibrium warm chemistry triggered by turbulent dissipation. The power of the combination between modelling and observations is also illustrated by observations of the CH+ cation that provide unique quantitative informations on the kinetic energy trail in the massive, multi-phase and turbulent circum-galactic medium of a galaxy group at redshift z = 2.8.

In this paper is presented the design and syntheis of a dynamic output feedback neural network controller for a non-holonomic mobile robot. First the dynamic model of a non-holonomic mobile robot is presented, in which these constraints are considered for the mathematical derivation of a feasable representation for this kind of robot. Then two control strategies are provided based on kinematic control for this kind of robot. The first control strategy is based on driftless control, this means, that considering that the velocity vector of the mobile robot is orthogonal to its restriction a dynamic output feedback and neural network controller is designed in order that the control action would be zero only when the velocity of the mobile robot is zero. The Lyapunov stability theorem is implemented in order to find a suitable control law. Then another control strategy is designed for trajectory tracking purposes, which similar to the driftless controller, a kinematic control scheme is provided but suitable to implement in more sophisticated hardware. In both control strategy a dynamic control law is provided along with a feedforward neural network controller, so in this way, by the Lyapunov theory the stability and convergence to the origin of the mobile robot position coordinates is ensured. Finally, two numerical experiment are presented in order to validate the theoretical results synthetized in this research study. Discussions and conclusions are provided in order to analyze the results found in this research study.