Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Aileen Oeberst and Roland Imhoff’s remarkable paper (Perspectives on Psychological Science 2023; 18: 1464-87). should be compulsory reading for all intelligence analysts. It offers a tantalisingly parsimonious explanation comprising the combination of strongly held prior 'beliefs' coupled with subsequent 'belief-consistent information processing' (akin to confirmation bias) - an explanation that simplifies understanding of a vast array of cognitive biases, and thereby suggests that all of these might be attenuated through the application of accessible analytical and assessment practices. What this means for intelligence analysis will be determined by the explicit and implicit 'beliefs' (or, more generally, ‘value[s]’) attributed to any evidence available, and any insight generated, to reduce decision-makers’ uncertainty and unsubstantiated certainty, and thereby offer them future advantage. Analysts are well aware that different sources of evidence (whether empirical, theoretical or entirely speculative) can assign different types and amounts of ‘prior value’ to the information available for intelligence analysis and assessment. Acknowledging such value as a potential driver of subsequent confirmation bias should help analysts guard against any inherent tendency to preference evidence solely on the basis that this was initially considered most ‘valuable’. Instead they should subject all evidence and all insight – regardless of perceived ‘value’ – to a consistent battery of systematic, rigorous and robust evaluation.

Microbes are the most prevalent and widely-distributed life form on planet Earth. They are also cognitive organisms with memory and superior problem-solving skills that use quantum phase transitions during their remarkably-effective gathering and dissemination of information. This narrative review explores the biological ramifications of human holobionts physically embodying the human microbiome and connecting to the Internet of Microbes (IOM) beyond our body. Within the review, we consider: 1) the ways in which our microbial co-partners exerted control over our ancestors and continue to influence our current human generation, 2) how they mold virtually every key aspect of our life and even remain with our body in death and 3) how inward-looking contemplative tools such as meditation and embodied cognition provide an ideal opportunity to connect to the microbial information super highway and tap the full range of human holobiont capacities.

Introduction: The primary objective of researchers in the biology of ageing is to gain a comprehensive understanding of the ageing process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human ageing. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in ageing.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Geriatric decisional capacity assessment is a complex medico-legal activity that evaluates normal subjects involved in specific civil matter like wealth transfer, access to treatment or voluntary hospitalization. Our objective was to evaluate how geriatric extrajudicial capacity exams impacted a general psychiatric unit over a decade. We also assessed the value of a surrogate biomarker (neutrophils to lymphocyte ratio) as a screening factor in the capacity assessment process. 72 cases were assessed in one psychiatric unit over a decade (2009-2018). As population was fast ageing, the total number of capacity exams per year doubled in time. None of the subjects had an active diagnostic of severe cognitive impairment or active psychiatric disease. The percentage of subjects receiving an “absence of capacity” conclusion remained constant over time (approx. 20% of all cases). 81% of the subjects within this subgroup had a clinical diagnostic of mild cognitive impairment compared to 46% in the “presence of capacity” subgroup (p<0.001). The surrogate biomarker neutrophils to lymphocyte ratio was significantly higher in the “absence of capacity” subgroup, mainly related to a cognitive impairment diagnostic. The ratio has to be validated by larger studies before to be included in the capacity assessment process as an early screening tool.

Financial capacity instruments are psychometric tools designed to evaluate individual decisional capacity based on financial decisions. As tests are complex and need special conditions for administration and evaluation, it is difficult to use them in daily geriatric clinics. Our scoping review objective was to evaluate existing financial capacity instruments from the perspective of simplicity and portability. We evaluated one English speaking knowledge database (Medline) using a dedicated MeSH terminology. The review yielded one independent instrument, The Semi-Structured Clinical Interview for Financial Capacity, that can be easy adapted for every-day clinical use. It is simple to understand and perform and do not need trained personnel for administration. It can be finalized in 15 minutes. Initially validated on 261 subjects (with different forms of cognitive impairment), it showed good accuracy and precision mainly in subjects with cognitive impairment. The test is less apt to detect early or fluctuating cognitive impairment. Simplicity, the main advantage of the test, allows gamification fact that increases portability. Familiar images (coins, money) that are used for performing simple tasks does not need complex translation and adaptation. In form of a game, the test is suitable for serial administration, increasing the chance for early capacity reduction detection. Results reflect a physician judgement related to the subjects’ capacity to understand and execute simple financial instructions and not financial proficiency scores. The main limitation of our review is that we investigated only one, English speaking, knowledge database. The scoping strategy generated a financial capacity instrument that can be used in geriatric clinics for early diagnostic of decisional capacity reduction. Further studies are needed to evaluate the reliability and validity of the test in conditions of serial administration and in populations having various financial experience.

Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear because abnormality is often absent in structural imaging findings. The purpose of the study was to determine whether machine learning-based models using functional magnetic resonance imaging (fMRI) biomarkers and demographic or neuropsychological measures at baseline could effectively predict 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically-matched healthy controls enrolled between September 2015 to August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to the significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after concussion. Approximately half of the patients experienced prolonged cognitive impairment at 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy=87.5%), 6 months (accuracy=83.3%), 1 year (accuracy=83.3%), and performed worse at 1-year follow-up compared to baseline assessment (accuracy=83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.

Mild Cognitive Impairment (MCI) is a clinical syndrome characterized by a moderate decline in one or more cognitive functions with a preserved autonomy in daily life activities [1]. MCI exhibits cognitive, behavioral, psychological symptoms [2]. The executive functions (EFs) are a set of key functions for everyday life and physical and mental health; and allow adapting the behavior to external changes [3-5]. Higher-level executive functions develop from basic EFs (inhibition, working memory, attentional control, and cognitive flexibility). They are planning, reasoning, problem- solving, and fluid intelligence (Gf) [3]. This systematic review investigates the relationship between higher-level executive functions and healthy and pathological aging, assuming the role of executive functions deficits as a predictor of cognitive decline. The systematic review was conducted according to the PRISMA Statement [6-7]. A total of 73 studies were identified. The results indicate that 65.8% of the studies confirm significant EFs alterations in MCI (100% problem solving, 71.4% fluid intelligence, 56.8% planning, 50% reasoning). These results seem to highlight a strong prevalence of higher-level executive functions deficits in MCI elderly than in healthy elderly.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

Background: Animal-assisted therapy has positive effects on cognitive function, depression, performance ability, and social functioning in elderly patients. The aim of this study was to evaluate the effects of rearing pet insects on the cognitive function of healthy elderly participants, with fMRI (functional magnetic resonance imaging) being used for this purpose. Methods: Community-dwelling elderly women (≥60 years) with normal cognitive function were enrolled during April 2015. They were randomized at a 1:1 ratio into two groups: insect-rearing and control (n=16) groups, with the insect-rearing group being further classified into two groups for analysis according to the subjects’ scores in the Wisconsin Card Sorting Test, WCST) at the first fMRI: insect-rearing group I with a relatively high score (n=13), and insect-rearing group II with a relatively low score (n=6). All subjects were educated on a healthy lifestyle for better cognitive function at every visit, and the insect-rearing groups received and reared crickets as pet insects. The fMRI was performed at baseline and after 8 weeks using the WCST as a stimulus. The WCST consisted of two variations, a high level baseline (HLB) and semi-WCST version. Results: There were no significant differences in the baseline characteristics among the three groups. There was a significant difference accuracy of the HLB–semi-WCST (p<0.05) in insect-rearing group II after 8 weeks from the baseline test. In the fMRI analysis involving the WCST reaction test, increased activation was observed in the right dorsal lateral prefrontal cortex and parietal cortex in insect-rearing group II when the semi-WCST, rather than the HLB, was performed. There were no significant differences in the other groups. Conclusion: The rearing of pet insects as an animal-assisted therapy is cost-effective, easy, and occupies little space. In this study, it showed positive effects on executive functions and performance improvement in elderly women. Further larger studies on the effects of pet insects on cognitive function are warranted.

This systematic review explores the cross-cultural validation of neuropsychological assessments and their clinical applications in cognitive behavioral therapy (CBT), focusing on culturally adapted CBT (CA-CBT) across diverse populations and settings. Methods: Following the PRISMA guidelines, a comprehensive search was conducted in multiple academic databases, including PubMed, PsycINFO, Scopus, and Web of Science. Keywords related to cognitive-behavioral therapy, cultural adaptation, and specific populations were used. Inclusion criteria encompassed randomized controlled trials (RCTs) and pilot studies that assessed CA-CBT for various mental health conditions. Results: The review included studies involving Chinese Americans, Latino caregivers, Syrian refugees, Jordanian children, Malaysian Muslims, Afghan refugees, Iraqi women, Japanese children and adolescents, and Tanzanian and Kenyan children. CA-CBT demonstrated significant effectiveness in reducing symptoms of depression, anxiety, PTSD, and psychosis. For instance, Research has shown that CA-CBT is more effective than standard CBT in reducing depressive symptoms among Chinese Americans and significantly lowering PTSD symptoms in Syrian refugee women. The method has been well-received and feasible in diverse populations, such as Jordanian children and Afghan refugees. Long-term benefits are promising, with sustained improvements reported in various studies. Additionally, digital and remote delivery methods have demonstrated potential for expanding the accessibility of CA-CBT. Conclusions: CA-CBT is a valuable and effective intervention for diverse cultural populations, significantly improving mental health outcomes. However, future research must address limitations such as small sample sizes, short follow-up periods, and variability in assessment tools. Studies should include larger and more diverse sample sizes, longer follow-up periods, rigorous control groups, and comprehensive outcome measures to further validate and enhance the application of CA-CBT across different cultural contexts.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

(1) Background: Substantial evidence that neural timing deficits are prevalent in developmental disorders, aging, and concussions resulting from a mild Traumatic Brain Injury (mTBI) is presented. We show that if timing deficits are remediated using low-level movement discrimination training, then high-level cognitive skills, including reading, attention, processing speed, and working memory improve substantially. (2) Methods: Two case studies are presented using MEG source imaging on an adult dyslexic, and a healthy older adult observed before and after training on movement discrimination two times/week for 8 weeks for adult dyslexic. (3) Results: We found improvements in reading, attention, processing speed, and working memory on neuropsychological tests. Substantial MEG signal increases in visual Motion Networks (V1, V3, MT, MST), Attention Networks (ACC, dlPFC, vlPFC and precuneous/ PCC areas) and Memory Networks (dlPFC). (4) Conclusions: Improving neural timing deficits before cognitive exercises to improve specific cognitive skills provides a rapid and effective method to improve cognitive skills. Improving the timing and sensitivity of low-level dorsal pathways, improving feedforward and feedback pathways, is essential to improve high-level cognitive skills. This adaptive training with substantial feedback shows cognitive transfer to tasks not trained on, significantly improving a person’s quality of life rapidly and effectively.

This study attempts to classify compound words on the basis of Cognitive Linguistics and compares their usage trends using Computational Linguistics. Using Noam Chomsky’s concept of deep and surface structures of a sentence, Lees treated compound words, not as separate units but as a kind of embedded sentences and hinted for possible presence of deep and surface structures in compound words, which this study tries to investigate. Then on the basis of the Idealized Cognitive Model proposed by Lakoff and Fauconnier, compound words have been classified into transparent, opaque and counterintuitive compound words. Using Google Books Corpus, this study also compares their usage trends. This is done using usage frequency, defined in this work, which is analogous to productivity for affixed words calculated by G.E.Booij. Each class of compound word formed on the basis of ICM is found to have different usage frequency. The possible reasons for this are discussed.

The communication space allows for the exchange of information and ensures the movement of material flows and passenger flows. By communication space, we mean the movement of information and material flows of various natures based on transport systems, in this case, air transport systems. The direction and intensity of these flows to varying degrees reflect the main social and economic processes. Time series reflecting the intensity of passenger flows and cargo transportation over a given time horizon were selected as a source of information used for analysis. An information-theoretical measure based on the assessment of entropy transfer between time series elements is used as a research tool. Based on the obtained paired estimates of entropy transfer between the selected time series, an entropy transfer matrix is formed, which allows considering a set of time series as a communication system within the framework of system analysis. The resulting matrices are used to form entropy transfer graphs, which allow investigating the properties of time series based on directed graph analysis methods. The article examines examples of the analysis of the cognitive model of transportation, the analysis of the regional communication space, and the analysis of changes in the global communication field.

Post-acute COVID-19 vaccination syndrome (PACVS) is distinguished from the normal post-vaccination state by altered receptor antibodies (Semmler et al. Vaccines 2023, 11, 1642). Here, we explore the symptoms registry and standard serum markers acquired in the above study to delineate the disease phenotype of PACVS. Symptoms reported by the participants overlapped with established complex dysautonomia syndromes (ME/CFS, POTS, MCAS, SFN). However, many participants were qualified for several (131/191) or none (31/191) of these syndromes. Unbiased clustering (modified Jaccard index) revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (&gt; 80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, vasomotor dysfunction, (ii) cardiovascular impairment, and (iii) cognitive impairment, headache, optic, oculo-motoric and acoustic dysfunctions were also frequently represented. Conspicuous serum markers encompassed increases in interleukins 6 and 8 and low fT3 levels (&gt; 80%), IgG-subclass imbalances and impaired iron-storage (&gt; 50%), and increases in sNFL (&gt; 30%). Serum markers were not correlated to specific symptoms or symptom clusters. A single and unique cause (i. e. SARS-CoV-2 vaccination) is improbable to trigger several distinct etiologies. Therefore, the symptoms and serological features observed in our study cohort probably represent facets of a single complex syndrome.

Knowledge is a property that measures the degree of awareness of an agent about a target in an environment. The goal in conventional intelligent and cognitive agent development is to build agents that can be trained to gain knowledge about a target. The definition and operations of this knowledge associated to the agent is not clear, whereas these are required for developing a reliable, scalable and flexible agent. In this paper, we provide a concise theoretical framework for the description and quantification of the knowledge property needed for an efficient design of cognitive and rational intelligent agents. We relate the quantification scheme to the epistemological description of knowledge and present many illustrative examples on the usefulness of the quantification scheme.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Spiritual intelligence had an impact on different biblical leaders, and in this text, we see some cases to serve as a sample (Joseph, Bezalel, and Daniel). In the Bible, this impact is demonstrated in innovations introduced by Joseph in Egypt, Bezalel the manager of the macro project of building in crisis time, Daniel the politician. It is the supreme intelligence and leaders are invited to make a shift from rationality to spirituality. The more leaders of organizations will use spiritual intelligence, the more leaders and followers will experience satisfaction, joy, accomplishment.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

To solve the problem of energy constraint and spectrum scarcity for cognitive radio wireless sensor networks (CR-WSNs), an underlay decode-and-forward relaying scheme is considered, where the energy constrained secondary source and relay nodes are capable of harvesting energy from a multi-antenna power beacon (PB) and using that harvested energy to forward the source information to the destination. Based on the time switching receiver architecture, three relaying protocols, namely, hybrid partial relay selection (H-PRS), conventional opportunistic relay selection (C-ORS), and best opportunistic relay selection (B-ORS) protocols are considered to enhance the end-to-end performance under the joint impact of maximal interference constraint and transceiver hardware impairments. For performance evaluation and comparison, we derive exact and asymptotic closed-form expressions of outage probability (OP) and throughput (TP) to provide significant insights into the impact of our proposed protocols on the system performance over Rayleigh fading channel. Finally, simulation results validate the theoretical results.

Virtual Reality (VR) is increasingly used in neuropsychological assessments due to its ability to simulate real-world environments. This study aimed to develop and evaluate the Trail Making Test in VR (TMT-VR) and investigate the effects of different interaction modes and gaming skills on cognitive performance. A total of 71 young female and male adults (aged 18-35) with high and low gaming skills participated in this study. Participants completed the TMT-VR using three interaction modes: eye-tracking, head movement, and controller. Performance metrics included task completion time and accuracy. User experience, usability, and acceptability of TMT-VR were also examined. Results showed that both eye-tracking and head movement modes significantly outperformed the controller in terms of task completion time and accuracy. No significant differences were found between eye-tracking and head movement modes. Gaming skills did not significantly influence task performance using any interaction mode. Participants reported high usability, acceptability, and user experience for the TMT-VR. Eye-tracking facilitated higher accuracy, while head movement higher speed. The TMT-VR offers high usability and user experience and is well accepted by the participants. The findings suggest that VR-based assessments can effectively measure cognitive performance without being influenced by prior gaming skills, indicating potential applicability for diverse populations.

Neural or mental simulation of actions is a powerful tool for allowing cognitive agents to develop Prospection Capabilities that are crucial for learning and memorizing key aspects for challenging skills. In previous studies we developed an approach based on the animation of the redundant human Body Schema based on the Passive Motion Paradigm (PMP). In this paper we show that this approach can be easily extended to hyper-redundant serpentine robots as well as to hybrid configurations where the serpentine robot is functionally integrated with a traditional skeletal infrastructure. A simulation model is analyzed in detail showing that it incorporates spatio-temporal features discovered in the biomechanical studies of biological hydrostats like the elephant trunk or the octopus tentacles. It is proposed that such generative internal model can be the basis for a cognitive architecture appropriate for serpentine robots, independent of the underlying design and control technologies. Although robotic hydrostats have received a lot of attention in the last decades, the great majority of research activities have been focused on the actuation/sensorial/material technologies that can support the design of hyperredundant soft robots as well as the related control methodologies. The cognitive level of analysis has been limited to motion planning, without addressing synergy formation and metal time travel. This is where the contribution of the paper is focused on.

Mirror Therapy (MT) and Cognitive Therapeutic Exercise (CTE) are two neurorehabilitation techniques based on neuroplasticity and designed to enhance the functionality of the upper limb. Therefore, the aim is to assess the effectiveness of the combination of CTE and MT with task-oriented training (TOT) on fine and gross motor skills of the affected hand, as well as the functionality of the affected upper limb, autonomy, independence, and quality of life (QoL) in patients with acute stroke. This longitudinal and multicenter study involved a sample of 120 participants selected randomly and consecutively. Three groups were formed, including a control group (CG) and two treatment groups, one with MT and the other with CTE. The functionality of the upper limb, fine and gross motor skills, the quantity and quality of use of the affected upper limb, autonomy, and QoL were evaluated using various scales validated in the Spanish population at the baseline, after 20 treatment sessions, and at three months of follow-up. ANCOVA analysis was conducted, revealing statistically significant differences between assessments in the CG compared to the experimental groups (GEs), indicating a notable improvement in overall functionality, fine and gross motor skills, autonomy, and QoL in the latter. However, there were no significant differences between the GEs. Therefore, the application of either of these experimental combinations is crucial for the motor recovery, functionality, and improvement of the quality of life of individuals who have suffered a stroke.

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

Despite the proliferation of Blockchain Metaverse projects, the inclusion of physically disabled individuals in the Metaverse remains distant, with limited standards and regulations in place. However, the article proposes a concept of the Metaverse that leverages emerging technologies, such as Virtual and Augmented Reality, and the Internet of Things, to enable greater engagement of disabled creatives. This approach aims to enhance inclusiveness in the Metaverse landscape. Based on the findings, the paper concludes that the active involvement of physically disabled individuals in the design and development of Metaverse platforms is crucial for promoting inclusivity. The proposed framework for accessibility and inclusiveness in Virtual, Augmented, and Mixed realities of decentralised Metaverses provides a basis for the meaningful participation of disabled creatives. The article emphasises the importance of addressing the mechanisms for art production by individuals with disabilities in the emerging Metaverse landscape. Additionally, it highlights the need for further research and collaboration to establish standards and regulations that facilitate the inclusion of physically disabled individuals in Metaverse projects.

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

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.

Interdisciplinary research consists of many levels and pathways. One research level that has emerged since the early 21st century is called integration science. Specifically, we focus on a research pathway that structurally integrates social sciences with theoretical physics from perspectives of dynamic analysis. Building on nearly 20 years of prior work, this paper proposes a basic theory of integration science, laying the theoretical foundation for its subsequent development. The significance of integration science operates on three levels. First, identifying structural connections between different disciplines helps in our holistic understanding of natural and social phenomena. Second, generally speaking, the current level of conceptualization and modeling in natural sciences, especially physics, is ahead of social sciences. Integration science research can help elevate the level of conceptualization and modeling in social sciences. Third, the structural similarity across different disciplines reflects the shared thinking of scientists from various fields. Integration science is not simply a synthesis of knowledge from different disciplines. The standard of integration science is to enable social sciences and natural sciences to share the same mathematical structures, thereby possessing a unified mathematical language for description. The empirical basis of integration science is discussed, proposing a unified theory of interdisciplinary scientific observation. This includes concepts like the directionality of scientific observation and the orthogonal principle, the concept of observational disturbance and the diagonal law, defining low and high disturbance quadrants, and discussing why different disturbance quadrants follow their respective mathematical paths. The basic theory of integration science is proposed. The application of category theory in integration science is introduced, along with the necessary semantic supplements. The fundamental concepts of integration mathematics are proposed, defining concepts like integration points, lines, plans, and bulks, and discussing their algebraic and functional analysis methods, thereby laying the mathematical foundation for the integration science. The structural force hypothesis is proposed, along with an axiomatic system of structural forces, thereby laying the philosophical foundation for integrative science. Based on prior work, specific cases of integrative points, lines, plans, and bulks are provided.

In this paper, we critically examine the burgeoning role of advanced computational methodologies in deciphering the complex tapestry of farm animal behaviors and emotions. Leveraging digital imaging and artificial intelligence, we unearth nuanced behavioral patterns and micro-expressions, offering predictive insights into animal emotional states. Sound vocalization analysis, often overlooked, emerges as a pivotal tool, decoding intricate communicative nuances and emotional undertones. Cognitive tests, including mirror and bias assessments, challenge long-standing perceptions, revealing surprising depths of animal self-awareness and cognitive sophistication. However, the paper also underscores the imperative of integrating these tools with a profound understanding of animal psyche, ensuring technology serves as an enhancer, not a replacement, of traditional observational methods. This research not only highlights the transformative potential of cognitive computing in animal welfare but also calls for a judicious application, ensuring technology augments, not undermines, the intrinsic value of human-animal interactions and understanding.

Detecting, tracking, and classifying unmanned aerial vehicles (UAVs) in a swarm presents significant challenges due to their small and diverse radar cross-sections, multiple flight altitudes, velocities, and close trajectories. To overcome these challenges, adjustments of the radar parameters and/or position of the radar (for airborne platforms) are often required during runtime. The runtime adjustments help to overcome the anomalies in the detection, tracking, and classification of UAVs. The runtime adjustments are performed either manually or through fixed algorithms, each of which can have its limitations for complex and dynamic scenarios. In this work, we propose the use of multi-agent reinforcement learning (RL) to carry out the runtime adjustment of the radar parameters and position of the radar platform. The radar used in our work is a multibeam multifunction phased array radar (MMPAR) placed onboard UAVs. The simulations show the cognitive adjustment of the MMPAR parameters and position of the airborne platform using RL helps to overcome anomalies in the detection, tracking, and classification of UAVs in a swarm. A comparison with other artificial intelligence (AI) algorithms shows that RL performs better due to runtime learning of the environment through rewards.

The concept of spiritual intelligence is currently at the focus of scientific debate. One of the most important problems is if it is a valid intelligence that meets the criteria developed by scholars. In this paper, I look at this idea in the context of Howard Gardner's theory of multiple intelligences and show some evidence from biology, neurology, and other scientific disciplines

One of the most rapidly advancing areas of deep learning research aims at creating models that learn to disentangle the latent factors of variation from a data distribution. However, modeling joint probability mass functions is usually prohibitive, which motivates the use of conditional models assuming that some information is given as input. In the domain of numerical cognition, deep learning architectures have successfully demonstrated that approximate numerosity representations can emerge in multi-layer networks that build latent representations of a set of images with a varying number of items. However, existing models have focused on tasks requiring to conditionally estimate numerosity information from a given image. Here we focus on a set of much more challenging tasks, which require to conditionally generate synthetic images containing a given number of items. We show that attention-based architectures operating at the pixel level can learn to produce well-formed images approximately containing a specific number of items, even when the target numerosity was not present in the training distribution.

Understanding behavioral factors associated with obesity is of importance in addressing this issue. This study examined the association between cognitive restraint, uncontrolled eating, emotional eating and body mass index (BMI) and amount of food plated, consumed, leftovers, and leftover food thrown into the trash (food wasted) in early adolescent girls nine to 13 years in O’ahu, Hawai’i (n = 93). Food plated, consumed, leftovers, and food wasted were estimated using a three-day mobile food record (mFR). Weight and height were measured to compute BMI (kg/m2). The three-factor eating questionnaire provided a score from 0 to 100 for cognitive restraint, uncontrolled eating, and emotional eating. Higher scores are indicative of greater cognitive restraint, uncontrolled eating, and emotional eating. Pearson’s correlation and general linear models were computed to examine the relationship between three factor eating scores, BMI, and food plated, consumed, leftovers, and food wasted. There was no clinically significant association between cognitive restraint and amount of food wasted. Cognitive restraint was positively correlated with BMI (r=0.36, p<0.001) and with BMI z score (r=0.40, p<0.001). Uncontrolled eating and emotional eating were positively correlated with amount of leftover food at dinner (r=0.30, p=0.006; r=0.33, p=0.003, respectively). Emotional eating was positively associated with percentage of leftover food at dinner (r=0.24, p=0.30). Additional research should examine the specific roles of cognitive restraint, uncontrolled eating, emotional eating and food waste in the development of obesity in adolescents.

Introduction: Diagnosing and managing Borrelia miyamotoi disease (BMD) is challenging due to its symptom overlap with Lyme disease (LD) and the lack of reliable laboratory diagnostics for BMD. This case study demonstrates the use of phage-based PCR (phb-PCR) to identify B. miyamotoi in a patient who had been bitten by ticks. Case presentation: A female patient aged 46 presented with joint and muscle pain, myalgic encephalomyelitis/chronic fatigue syndrome, and cognitive impairment after multiple tick bites in Europe. The patient was assessed for LD at the National Reference Centre in Strasbourg using Enzyme-linked immunosorbent assay (ELISA) and immunoblot. Additional diagnostics involved screening for Bartonella and Anaplasma antibodies using indirect immunofluorescence, and tests for antinuclear antibodies to check for autoimmune conditions. All serological and immunological tests yielded negative results. However, the phb-PCR identified B. miyamotoi. Consequently, the patient received treatment for BMD with a regimen of intravenous ceftriaxone, oral azithromycin, and additional intravenous vitamin and mineral therapy. Post-treatment evaluations showed significant improvements in pain levels, cognitive abilities, and fatigue. Conclusion: This case highlights the importance of direct diagnostic methods like phb-PCR for identifying BMD when serological tests fail. Clinicians should consider B. miyamotoi testing for accurate and timely management of complex TBDs.

Experiential learning, defined as the result, source, or context of knowledge obtained from direct experience, is increasingly bolstered by technology and human-computer interaction (HCI) principles and protocols. This article will describe how technology-based human-computer interaction (HCI) has been used in experiments to enhance direct knowledge experience. In this paper, immersive technologies (such as Virtual Reality, Augmented Reality, and haptics) will be described based on cognitive learning theory, empirical research and practical experience gained from implementing cutting-edge technology and maximizing HCI principles in constructive learning. Additionally, this article will describe how AI can be used to create individualized learning environments according to a student's needs in the future. While cost, technical issues and specialised trainings are the obstacle to deliver personalized learning experiences especially to economically disadvantaged students, technological change opportunities are projected, and these technologies will take educational outcomes to the next level.

The epistemology of the traditional risk assessment examined has a taxonomy based upon deterministic, behaviouristic and compatibilist methodologies which are likely driven by neo-liberal market related requirements for bigger, faster cheaper wind-turbines. Analysis of available risk assessments suggested that there is no conscious effort to deceive the reader although the intended audience is unclear. The language, and scoring mechanisms utilized indicates the presence of conformity bias, confirmation bias, and numerical inconsistency leading to data ossification. By reverse engineering risk assessment content, Pragmatic and Social Psychological aspects can be investigated, and the adequacy of the document can be evaluated using evidence-based models.

Eating disorder (ED) symptoms often co-occur with nonsuicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. One hundred and five community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI.

A smart city is a futuristic approach that evolves with new technologies. It can start as a simple community and evolve into future cities. In most developing countries, where the population growth is faster, and where the organization and the urbanization are slower, there is a serious need for a framework for progressive change towards sustainable cities. This article discusses the level of intelligence of smart city components and proposes indicators as well as a methodology for measuring intelligence based on the objectives to be achieved as well as a certain number of technical requirements and some cognitive processes implemented.

In the following article, we analyzed a variable present in the ISTAT-BES dataset, namely "People You Can Count On"-PYCC for the Italian regions. Following an analysis of the time series aimed at highlighting the trends of the regions, we created a clustering with a k-Means algorithm optimized with the Silhouette coefficient. The data shows the presence of two clusters. We then present an econometric model aimed at estimating the value of PYCC based on a set of socio-economic variables. The results are also discussed in light of the economic policy implications.

Background: Youth experiencing homelessness (YEH) in East Asia Pacific (EAP) represent one of the most at-risk populations due to cultural and geographical factors. Effective mental health interventions, primarily researched in Western contexts, may not fully apply to YEH in EAP. Their lack of stable shelter, disrupted social networks, and limited access to mental health services elevate their susceptibility to adverse mental health, making urgent interventions essential to address their needs. Objective: To explore and provide systematic evidence on the types of mental health services and interventions for YEH in EAP and their impact on overall quality of life and wellbeing. Methods: Electronic databases(e.g., Medline, PsychInfo, PubMed, Scopus) were systematically searched(publication dates between 01/01/1990-13/05/2023), as well as additional online resources specific to homelessness. Articles were screened, and a critical appraisal assessed the quality of the included studies. Results: Eight studies with different interventions were identified in Indonesia(n = 2), Malaysia(n = 1), South Korea(n = 3), and The Philippines(n = 1). These were thematically clustered into six categories: art, cognitive behavioural therapy, life skills education, resilience enhancement, family strengthening and government interventions/services. Conclusion: This review highlights effective mental health interventions’ positive impact on YEH mental health outcomes and quality of life in EAP, stressing the urgent need to implement socio-culturally sensitive services. Future research should address knowledge gaps through comprehensive studies covering diverse EAP regions and populations, prioritising socio-culturally specific psychological measures.

Psychosis in Alzheimer's disease (AD) is a prevalent phenomenon, marked by delusions and hallucinations, along with other neuropsychiatric symptoms such as agitation, depression, anxiety, and apathy. These neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD), affect up to 97% of Alzheimer's patients. The presence of psychosis in AD significantly impacts patients' daily lives and places a considerable burden on caregivers. The development of AD-related psychosis (ADP) is influenced by a range of factors, including genetic predispositions and life-acquired factors. AD affects cognitive function and various brain regions, resulting in widespread brain atrophy. In addition to its neurological impact, AD can induce pathological physiological changes that serve as biomarkers for ADP. Research efforts have focused on developing pharmacological treatments for psychosis in AD, aiming to minimize side effects. Brexpiprazole has emerged as a promising medication for ADP, alongside other antipsychotics. Treatment approaches for ADP extend beyond pharmacology, incorporating methods such as sensory stimulation and digital therapeutics. This review will explore the characteristics of psychosis in Alzheimer's disease, the pathological underpinnings of ADP, and the current therapeutic landscape, highlighting emerging opportunities for managing this challenging condition.

(1) Background: Adolescent well-being is a multifaceted construct embedded in family, school, and peer socialization contexts. By adopting a social-psychological perspective we test the association between three sources of support (parents, teachers, peers) and specific components of subjective well-being (cognitive, affective, global-and-domain-specific) to determine whether there is a functional specialization of the role that these crucial socialization agents play for adolescents to attain well-being in specific life domains. (2) Methods: Cross-sectional Albanian data from Wave 3 of the Children’s Worlds International Survey (www.isciweb.org) were used, including 2,339 adolescents (age range 9-13; girls = 49.3%). A structural equation model (SEM) was employed to explore associations between supportive relationships with parents, teachers, and peers and adolescent well-being. (3) Results: Findings support a functional specialization hypothesis as parental support was significantly related to global cognitive and affective well-being; teacher support was significantly related with school satisfaction; and significant relations were found between peer support and almost all well-being variables (context-free, domain-based life satisfaction and affective subjective well-being). (4) Conclusions: Findings contribute to a more nuanced understanding of the role of supportive relationships with adults and peers in adolescents’ proximal socialization contexts (family, school, peer groups) and specific components of subjective well-being.

It is one of the central goals of cognitive neuroscience to understand how structure and function relate in the brain. We review how cognitive function characterization has been approached in the past. In addition, we examine the ongoing efforts, as well as the implications for the future. Clinical studies on patients with lesions have provided key insights into the relationship between brain areas and behavior over the past century. We describe cognitive function according to localization considering these early efforts for characterization. We chose a perceptual-cognitive function, namely body perception, to describe our current efforts. Using body perception as an example, we summarize contemporary techniques. Finally, we outline the trajectory of current progress into the future and discuss the implications for clinical and basic neuroscience.

A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

The present study was developed based on the data of The PDWAVES Consortium (www.pdwaves.eu) and the PharmaCog project. The Partners and institutional affiliations are reported on the cover page of this manuscript. In this study, the clinical, neuropsychological, and magnetic resonance imaging data collection and analysis in patients with ADMCI and healthy control participants were partially supported by the funds of “Ricerca Corrente 2022-2023” (Italian Ministry of Health) to the IRCCS Synlab SDN of Naples (Italy), IRCCS Ospedale San Martino of Genoa (Italy), Oasi Research Institute-IRCCS, Troina (Italy), IRCCS Fatebenefratelli of Brescia (Italy), and IRCCS San Raffaele Pisana of Rome (Italy). Prof. Claudio Del Percio’s and Dr. Roberta Biundo’s work for this study was supported by funds of the “PRIN-2022” project entitled "AmyEEG” (Italian Ministry of University and Research, Prot. 2022FJAXY8). At the same time, Prof. Claudio Babiloni’s work was supported by funds of the “Horizon Marie S. Curie Doctoral Network ” project entitled "CombiDiag” (European Committee, Proposal: 101071485).

As the global population ages, the prevalence of neurodegenerative diseases has become a major public health concern. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks—such as genomic instability, telomere attrition, and neuroinflammation—and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

This research addresses the strategic issue of why key decision-makers fail to foresee potential extreme ‘black swan’ events. Following a review of the literature, a conceptual framework is developed that identifies two types of organisational blindness that are reflected in Tetlock’s hedgehog cognitive thinking style, being the oversimplification of uncertainty (e.g., inductive biases) and an unquestioned, top-down, reference narrative. This framework is tested using a case study approach and qualitative analysis of secondary data sources available from the Royal Commission of Inquiry and other published reports following the 2010 methane explosion at the Pike River Coal Ltd’s mine (Pike) in New Zealand, that killed 29 miners and caused the loss of all funds invested. The results indicate that the combined effect of both blindness’s meant that Pike’s collective intelligence was limited, and for the three key decision-makers at the Pike River mine, some type of extreme ‘black swan’ event was apparently inevitable. This research provides theoretical and practical contributions to the analysis of business and public policy decision-making under uncertainty.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Cognitive impairment in older adults is associated with poor gait performance, physical decline, falls and poor quality of life. This paper analyzes the feasibility and efficacy of a tango-based in-tervention in older people with cognitive impairment living in nursing homes. A multicenter study, with pre and post-test, was carried out. Intervention attendance, well-being, physical abilities (Short Physical Performance Battery), walking performance, functional capacities (Katz Index), and quality of life (Quality of Life in Alzheimer’s Disease) were assessed. Fifty-four participants (84.9 ± 6.7 years, Mini Mental State Examination 14.5 ± 7.4) completed the protocol. Intervention attendance was 92%, and the mean subjective well-being after each session was 4.5 ± 0.5 (on a five-point scale). Statistically significant improvement was found in the quality of life (p = 0.030). Non statistically significant changes were found in walking performance, physical abilities, or in functional capacities. The study shows feasibility and suggests evidence for the effects of Tango therapy on well-being and quality of life. Further studies are necessary to contrast these findings and to verify the role of Tango interventions as a holistic approach to prevent functional decline in older people with cognitive impairment.

Healthy aging among older adults requires the maintenance of good physical and cognitive activity. However, in the natural course of aging, older adults usually experience a decline in their physical and cognitive activity, causing an increasingly sedentary lifestyle. Some older adults may not have a choice but to become increasingly sedentary as they age due to injury or deteriorated physicality. As such they require a manner of assistive technologies to aid in their daily lives and activities to maintain healthy cognitive function. Social Robots are a newer form of assistive technology, specifically designed for social interactions and gameplay. As with other assistive technologies, compliance barriers to the acceptance and use of social robots and types of meaningful, seated activities among older adults are expected. To better explore this phenomenon, improve quality of life and understand what drives older adults to accept and use newer forms of technology like social robots, this research conjoins two conceptual frameworks: The Activity Theory of Aging (ATA) and the Unified Theory of Acceptance and Use of Technology (UTAUT). As social robots hold great promise for improving the quality of life for older adults, exploring what driving factors could enable their greater acceptance and use is essential to furthering this field of study within Australia.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

This research explores the predictive capabilities of autonomous driving systems by integrating human factor considerations within the context of safety-critical events. Recognizing the significance of human behaviors in influencing driving dynamics, the study employs advanced modeling techniques to enhance the accuracy of predictions in scenarios that demand heightened safety measures. Traditional rule-based systems and monotonic logic often fall short in addressing the complexities of safety-critical events. To overcome these limitations, the research proposes the application of non-monotonic logic, allowing for flexible and adaptive reasoning that accommodates exceptions and context-specific information.The study emphasizes the importance of incorporating individual differences among drivers, such as risk-taking tendencies, reaction times, decision-making processes, and driving styles. By considering these human factors, the research aims to develop realistic and accurate autonomous driving models that capture the nuances of real-world driving scenarios, especially in safety-critical situations. The predictive model takes into account both internal and external factors, enabling the autonomous system to anticipate and respond effectively to unforeseen events.The primary goal is to provide autonomous vehicles with the capability to make plausible inferences, handle conflicting data, and adapt their behavior in real-time during safety-critical events. The proposed model integrates personalized cognitive agents for each driver, incorporating their unique preferences, characteristics, and needs. This personalized approach aims to optimize the safety and efficiency of autonomous driving, contributing to the ongoing evolution of intelligent transportation systems.In conclusion, this research contributes to advancing the field of autonomous driving by introducing a predictive model that leverages human factor considerations to enhance safety in safety-critical events. The incorporation of non-monotonic logic and individualized cognitive agents signifies a comprehensive approach to address the challenges associated with predicting autonomous driving behavior, paving the way for safer and more reliable autonomous vehicles in dynamic and unpredictable environments.

As education continues to evolve in response to technological advancements, the concept of Education 5.0 has gained prominence. However, it is crucial to critically analyze the limitations and challenges of this model. This article presents a comprehensive examination of Education 5.0, identifies its drawbacks, and proposes a vision for Education 6.0. Through insightful case studies and discussions, this article aims to provide a nuanced perspective on the future of education.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

The intricate interplay between driver cognitive dysfunction, mental workload (MWL), and heart rate variability (HRV) provides a captivating avenue for investigation within the domain of transportation safety studies. This article presents a comprehensive review and examines cognitive hindrance stemming from mental workload and heart rate variability. It scrutinizes the mental workload experienced by drivers by leveraging data gleaned from prior studies that employed heart rate monitoring systems and eye tracking technology, thereby illuminating the correlation between cognitive impairment, mental workload, and physiological indicators such as heart rate and ocular movements. The investigation is grounded in the premise that the mental workload of drivers can be assessed through physiological cues, such as heart rate and eye movements. The study discovered that heart rate variability (HRV) and infrared (IR) measurements played a crucial role in evaluating fatigue and workload for skilled drivers. However, the study overlooked potential factors contributing to cognitive impairment in drivers and could benefit from incorporating alternative indicators of cognitive workload for deeper insights. Furthermore, investigated driving simulators demonstrated that an eco-safe driving Human-Machine Interface (HMI) significantly promoted safe driving behaviors without imposing excessive mental and visual workload on drivers. Recommendations were made for future studies to consider additional indicators of cognitive workload, such as subjective assessments or task performance metrics, for a more comprehensive understanding.

The European Space Agency (ESA) defines as Earth observation (EO) Level 2 information product a single-date multi-spectral (MS) image corrected for atmospheric, adjacency and topographic effects, stacked with its data-derived scene classification map (SCM), whose thematic map legend includes quality layers cloud and cloud-shadow. ESA EO Level 2 product generation is an inherently ill-posed computer vision (CV) problem never accomplished to date in operating mode by any EO data provider at the ground segment. Herein, it is considered: (I) necessary not sufficient pre-condition for the yet-unaccomplished dependent problems of semantic content-based image retrieval (SCBIR) and semantics-enabled information/knowledge discovery (SEIKD) in multi-source EO big data cubes. (II) Synonym of EO Analysis Ready Data (ARD) format. (III) Equivalent to a horizontal policy for background developments in Space Economy 4.0. In compliance with the GEO-CEOS Quality Assurance Framework for EO Calibration/Validation guidelines, to contribute toward filling an analytic and pragmatic information gap from multi-sensor EO big data to timely, comprehensive and operational EO value-adding information products and services, this work presents an innovative AutoCloud+ CV software toolbox for cloud and cloud-shadow quality layer detection in ESA EO Level 2 product. In vision, spatial information dominates color information. Inspired by this true-fact, the inherently ill-posed AutoCloud+ CV software was conditioned, designed and implemented to be “universal”, meaning fully automated (no human-machine interaction is required), near real-time, robust to changes in input data and scalable to changes in MS imaging sensor’s spatial and spectral resolution specifications.