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.

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.

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.