High-level Functions Research Articles

Reality and imagination intertwined: A sensorimotor paradox interpretation

As a hypothesis on the origins of mind and language, the evolutionary theory of the sensorimotor paradox suggests that capacities for imagination, self-representation and abstraction would operate from a dissociation in what is known as the forward model. In some studies, sensory perception is understood as a system of prediction and confirmation (feedforward and feedback processes) that would share common yet distinct and overlapping neural networks with mental imagery. The latter would then mostly operate through internal feedback processes. The hypothesis of our theory is that dissociation and parallelism between those processes would make it less likely for imaginary prediction to match and simultaneously coincide with any sensory feedback, contradicting the stimulus/response pattern. The gap between the two and the effort required to maintain this gap, born from the development of bipedal stance and a radical change to our relation to our own hands, would be the very structural foundation to our capacity to elaborate abstract thoughts, by partially blocking and inhibiting motor action. Mental imagery would structurally be dissociated from perception, though maintaining an intricated relation of interdependence. Moreover, the content of the images would be subordinate to their function as emotional regulators, prioritising consistency with some global, conditional and socially learnt body-image. As a higher-level and proto-aesthetic function, we can speculate that the action and instrumentalisation of dissociating imagination from perception would become the actual prediction and their coordination, the expected feedback.

Time scale analysis of enzymatic reduction of uric acid in a microfluidic biomedical device

Time Scale Analysis (TSA) is an investigative tool used in engineering design to identify locations in processes that should be a focus of Process Intensification (PI). Furthermore, TSA points to process variables and parameters that could be used to advance and measure PI improvement. However, TSA cannot suggest any specific design solution to intensify process performance. Instead, design engineers should use their fundamental knowledge and creative intelligence to specify detailed design transformations. TSA will then provide a specific quantitative measure of the improvement. TSA implementation improves an explicitly defined process performance, thus helping achieve process intensification goals. TSA is based on first principles, and it utilizes Characteristic Times (CT) such as diffusion, mean residence, and reaction times to improve an existing process. In this study, we specifically consider microfluidic biomedical devices. To illustrate the genesis of CT and TSA, we start by developing a mathematical model of an enzymatic degradation process in a biomedical device called iCore based on mass, momentum, and kinetic equations. After introducing user-defined scaling parameters, we extract CTs pertinent to the enzymatic degradation of uric acid in this microfluidic biomedical device. Diffusion coefficients, microchannel architectural characteristics, enzyme loading, hydrogel thickness, and characteristic parameters of enzyme kinetics are the parameters and process variables incorporated in this analysis. Finally, we compared the extracted CTs with a COMSOL Multiphysics parametric study to demonstrate how time scale analysis as a design tool and adjusting design parameters, such as diffusion coefficient, hydrogel layer thickness, substrate concentration, and enzyme concentration, can enhance the enzymatic reaction process without a need for complex computational modeling. It is crucial to recognize that pertinent CTs can be determined by understanding the type and nature of the observed process, previous experience, published data, and other foundational engineering design work. There is no need for mathematical modeling and numerical simulations to identify and acknowledge the CTs relevant and essential to the observed process; in this work, we only illustrate the principal origin of CTs via a detailed mathematical model of the process, as previously reported by Jovanovic et al. Therefore, in a routine application of TSA, it is important to remember that mathematical modeling and detailed numerical simulations are not necessary. This is a very comforting fact when TSA is deployed as a tool in higher-level process design functions. The investigations on how best to apply TSA in these higher level design functions such as Process Intensification, scale-up/numbering-up, change of device architecture, change of operating conditions, change of process feed characteristics, change of material physical and chemical properties, parametric optimization of the system for various objective functions, and techno-economic analysis, are yet to be studied and reported.

B-071 Unraveling Histamine Intolerance: Exploring DAO Quantity, Elimination Ratios and Cofactor Influences

Abstract Background Non-allergic reactions to food, often triggered by biogenic amines like histamine, result in symptoms such as headache, rhinitis, respiratory issues, digestive complaints, and eczema. The symptomatic overlap between histamine intolerance (HIT) and allergies may contribute to potential underdiagnosis. Limited data impedes precise incidence determination, but estimates suggest 1-3% of the population is affected, with increasing cases anticipated as knowledge and diagnostic tools for HIT advance. Despite histamine's physiological importance, elevated levels pose health risks. HIT arises when ingested or internally released histamine surpasses rapid breakdown capacity. Studies link HIT to DAO deficiency and/or impaired DAO activity, often in subgroups with genetic, pathological, or pharmacological factors. DAO cofactor deficiencies like copper, zinc, vitamin C or vitamin B6 may exacerbate DAO impairment. The trial aimed to explore the relationship of histamine elimination, DAO quantity, and essential cofactors for DAO activity. Methods Serum samples from 40 patients underwent analysis for DAO quantity and histamine elimination ratio using Immundiagnostik AG test kits. ELISA quantification employed a sandwich technique with polyclonal antibodies against recombinant DAO. Low DAO levels (< 3 U/ml) indicated histamine intolerance, moderate levels (3 - 10 U/ml) suggested probability, and high levels (< 10 U/ml) initially ruled out intolerance. Histamine elimination efficiency was assessed by comparing spiked sample levels at 0 and 24 hours after incubation, gauging histamine breakdown mechanisms without directly measuring enzyme quantity. Histamine elimination > 40% indicated unlikely intolerance, 25 - 40% (moderate) suggested probability, and < 25% (poor) indicated likelihood. Additionally, vitamin B6 influence was explored using Immundiagnostik AG's microbiological ID-VIT Test system, spiking samples with DAO for supplementation. Six samples with varying B6 levels underwent investigation. Results The investigation revealed that DAO quantity and histamine elimination highlight the enzyme's pivotal role. Distinctions emerged in histamine intolerance classification, with more than 25% of the population showing reduced elimination in samples with moderate DAO levels (3-10 U/mL), and more than 10% showing reduced elimination in samples with high DAO levels (>10 U/mL), suggesting potential DAO inhibition contributing to impaired histamine breakdown. Analyses based on functional vitamin B6 levels demonstrated varying responses to DAO supplementation. Samples with high functional B6 levels (>20 µg/l) showed a 20% increase in elimination with DAO supplementation of 3 U/mL. In contrast, samples with lower B6 levels (<7 µg/l) exhibited minimal to no additional elimination, despite supplemental DAO at 6 U/mL. These findings underscore the nuanced interplay among DAO levels, histamine elimination, and the influence of vitamin B6, providing insights into factors impacting histamine metabolism across diverse patient profiles. Conclusions The data unveil a high potential for differential diagnosis, particularly in the realm of moderate to high DAO quantity, where the dependence on DAO inhibition yields a different classification of HIT probability. Analyzing DAO cofactors, such as vitamin B6, emerges as a valuable complementary tool for the diagnosis and treatment of HIT. These findings underscore the importance of considering DAO levels, their inhibition, and cofactors in a comprehensive approach to enhance the accuracy of HIT assessment and guide effective therapeutic interventions.

Robust entropy rate estimation for nonstationary neuronal calcium spike trains based on empirical probabilities

Objective. Temporal patterns in neuronal spiking encode stimulus uncertainty, and convey information about high-level functions such as memory and cognition. Estimating the associated information content and understanding how that evolves with time assume significance in the investigation of neuronal coding mechanisms and abnormal signaling. However, existing estimators of the entropy rate, a measure of information content, either ignore the inherent nonstationarity, or employ dictionary-based Lempel-Ziv (LZ) methods that converge too slowly for one to study temporal variations in sufficient detail. Against this backdrop, we seek estimates that handle nonstationarity, are fast converging, and hence allow meaningful temporal investigations.Approach. We proposed a homogeneous Markov model approximation of spike trains within windows of suitably chosen length and an entropy rate estimator based on empirical probabilities that converges quickly.Main results. We constructed mathematical families of nonstationary Markov processes with certain bi/multi-level properties (inspired by neuronal responses) with known entropy rates, and validated the proposed estimator against those. Further statistical validations were presented on data collected from hippocampal (and primary visual cortex) neuron populations in terms of single neuron behavior as well as population heterogeneity. Our estimator appears to be statistically more accurate and converges faster than existing LZ estimators, and hence well suited for temporal studies.Significance. The entropy rate analysis revealed not only informational and process memory heterogeneity among neurons, but distinct statistical patterns in neuronal populations (from two different brain regions) under basal and post-stimulus conditions. Taking inspiration, we envision future large-scale studies of different brain regions enabled by the proposed tool (estimator), potentially contributing to improved functional modeling of the brain and identification of statistical signatures of neurodegenerative diseases.

No evidence for unconscious initiation and following of arithmetic rules: A replication study.

The field of consciousness studies has yielded various-sometimes contradicting-accounts regarding the function of consciousness, ranging from denying it has such function to claiming that any high-level cognitive function requires consciousness. Empirical findings supporting both accounts were reported, yet some of them have been recently revisited based on failures to replicate. Here, we aimed at replicating a remarkable finding reported by Ric and Muller (2012); participants were able to follow an unseen instruction, integrate it with a subsequently presented pair of unseen digits, and accordingly either add the digits (resulting in a priming effect), or simply represent them. This finding thus demonstrates unconscious task-switching, temporal integration (involving mental chaining), and arithmetic operation. Finding such high-level processes in the absence of awareness is of pivotal importance to our understanding of consciousness, as it challenges prominent theories in the field (e.g., the global neuronal workspace). Accordingly, in light of the self-correction wave in psychological science in general and in the field of consciousness studies in particular, we report here a preregistered replication aimed at testing the reproducibility of this finding, while also better controlling for subjects' awareness of both the instruction and the digits. Across two highly powered experiments, our results failed to replicate the original effect. We, therefore, conclude that the current evidence does not support the claim that arithmetic operations (specifically, addition) can be flexibly initiated without awareness, in line with the current arguments for a more limited scope of unconscious processing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhanced classification and severity prediction of major depressive disorder using acoustic features and machine learning.

Previous studies have classified major depression and healthy control groups based on vocal acoustic features, but the classification accuracy needs to be improved. Therefore, this study utilized deep learning methods to construct classification and prediction models for major depression and healthy control groups. 120 participants aged 16-25 participated in this study, included 64 MDD group and 56 HC group. We used the Covarep open-source algorithm to extract a total of 1200 high-level statistical functions for each sample. In addition, we used Python for correlation analysis, and neural network to establish the model to distinguish whether participants experienced depression, predict the total depression score, and evaluate the effectiveness of the classification and prediction model. The classification modelling of the major depression and the healthy control groups by relevant and significant vocal acoustic features was 0.90, and the Receiver Operating Characteristic (ROC) curves analysis results showed that the classification accuracy was 84.16%, the sensitivity was 95.38%, and the specificity was 70.9%. The depression prediction model of speech characteristics showed that the predicted score was closely related to the total score of 17 items of the Hamilton Depression Scale(HAMD-17) (r=0.687, P<0.01); and the Mean Absolute Error(MAE) between the model's predicted score and total HAMD-17 score was 4.51. This study's results may have been influenced by anxiety comorbidities. The vocal acoustic features can not only effectively classify the major depression and the healthy control groups, but also accurately predict the severity of depressive symptoms.

Distinct mechanisms and functions of episodic memory.

The concept of episodic memory (EM) faces significant challenges by two claims: EM might not be a distinct memory system, and EM might be an epiphenomenon of a more general capacity for mental time travel (MTT). Nevertheless, the observations leading to these arguments do not preclude the existence of a mechanically and functionally distinct EM system. First, modular systems, like cognition, can have distinct subsystems that may not be distinguishable in the system's final output. EM could be such a subsystem, even though its effects may be difficult to distinguish from those of other subsystems. Second, EM could have a distinct and consistent low-level function, which is used in diverse high-level functions such as MTT. This article introduces the scenario construction framework, proposing that EM crucially rests on memory traces containing the gist of an episodic experience. During retrieval, EM traces trigger the reconstruction of semantic representations, which were active during the remembered episode, and are further enriched with semantic information, to generate a scenario of the past experience. This conceptualization of EM is consistent with studies on the neural basis of EM and resolves the two challenges while retaining the key properties associated with EM. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Longitudinal Assessment of Selective Motor Dysfunction in Service Members With Combat-Related Mild TBI.

Evaluations of clinical outcomes in service members with mild traumatic brain injury (TBI) sustained in combat have largely focused on neurobehavioral and somatic symptoms, neurocognitive functioning, and psychological/psychiatric health. Questions remain regarding other domains, such as gross or fine motor abilities, that could be impacted and are mission-critical to functional warfighters. The objective of the current study was to evaluate longitudinal motor function in U.S. Military personnel with and without mild TBI sustained in combat to assess the possible long-term impact. Data from the EValuation Of Longitudinal outcomes in mild TBI active duty military and VEterans (EVOLVE) study were leveraged for analysis. The EVOLVE study has evaluated and followed service members from combat and following medical evacuation with and without blast-related mild TBI, as well as blunt impact mild TBI, and noninjured combat-deployed service members, tracking 1-, 5-, and 10-year outcomes. Longitudinal demographic, neuropsychological, and motor data were leveraged. Cross-sectional differences in outcomes at each year among the 4 injury groups were assessed using rank regression, adjusting for age, education, sex, branch of service (Army vs. other), subsequent head injury exposure, and separation from service. To understand the possible performance impact of time on all the measures, mixed-effects rank regression was employed, assessing time with adjustments for group, age, education, subsequent head injury exposure, and service separation status, followed by Benjamini-Hochberg correction for multiple comparisons. Evaluation for cognitive performance across 19 primary measures of interest at 1, 5, and 10 years did not identify any significant differences; however, gross motor function was found to be significantly different across groups at all time points (adjusted P < .001 at 1 year, P = .004 at 5 years, and P < .001 at 10 years) with both TBI groups consistently performing slower on the 25-Foot Walk and Grooved Pegboard than the nonblast control groups. While there were no cross-sectional differences across groups, many cognitive and motor measures were found to have significant changes over time, though not always in the direction of worse performance. Selective motor impairment in both TBI groups was identified compared to nonblast controls, but all groups were also found to exhibit a level of motor slowing when comparing performance at 1- to 10-year follow-ups. Assessment of gross motor function reflected a consistent pattern of significantly slower performances for blast and nonblast TBI groups compared to controls, over all follow-up intervals. Fine motor function performance reflected a similar significant difference pattern at 1- and 5-year follow-up intervals, with a reduced difference from control groups at the 10-year follow-up. Maintenance of high-level motor functions, including overall motor speed, coordination, and reaction time, is a primary component for active warfighters, and any motor-related deficits could create an increased risk for the service member or unit. While the service members in this longitudinal study did not meet criteria for any specific clinical motor-related diagnoses or movement disorders, the finding of motor slowing may reflect a subclinical but significant change that could be a focus for intervention to return to preinjury levels.

Human-unique brain cell clusters are associated with learning disorders and human episodic memory activity.

The advanced evolution of the human cerebral cortex forms the basis for our high-level cognitive functions. Through a comparative analysis of single-nucleus transcriptome data from the human neocortex and that of chimpanzees, macaques, and marmosets, we discovered 20 subgroups of cell types unique to the human brain, which include 11 types of excitatory neurons. Many of these human-unique cell clusters exhibit significant overexpression of genes regulated by human-specific enhancers. Notably, these specific cell clusters also express genes associated with disease risk, particularly those related to brain dysfunctions like learning disorders. Furthermore, genes linked to cortical thickness and human episodic memory encoding activities show heightened expression within these cell subgroups. These findings underscore the critical role of human brain-unique cell clusters in the evolution of human brain functions.

Outcomes of Surgical Treatment for Multiligament Knee Injuries in a Cohort Including Competitive Athletes With Long-Term Follow-Up.

There is a paucity of outcomes data on surgical reconstruction for multiligament knee injury (MLKI) in the orthopaedic literature. To examine functional and return-to-sports (RTS) outcomes and revision rates after single-stage reconstruction for MLKIs in a cohort containing a large proportion of competitive athletes over a 20-year period. Case series; Level of evidence, 4. We identified all patients at our institution who underwent surgical reconstruction for an anterior cruciate ligament (ACL) or bicruciate (ACL-posterior cruciate ligament) MLKI between 2001 and 2020 and had ≥2 years of postoperative outcome data. Patient-reported outcomes were evaluated using the International Knee Documentation Committee (IKDC) form, a surgical satisfaction survey, and questions about subsequent knee surgery and RTS administered via telephone. Summary statistics for all outcomes data were calculated, and predictors of IKDC scores at follow-up were examined using univariable linear regression. Out of 151 patients eligible for this study, outcomes data were collected in 119 patients (79%). The mean follow-up time was 8.3 ± 4.4 years, and the mean IKDC score at follow-up was 79 ± 17. A total of 83 competitive athletes were included; 62 of these athletes attempted to return to preinjury sport. Among the 62 who attempted RTS, 50 (81%) were successful, and 12 were unable to return due to limitations from their surgery. At follow-up, 112 of the overall cohort of 119 patients (94%) were either satisfied or very satisfied with their surgical outcome, and 91% stated the surgery met or exceeded their expectations. In addition, 24% had subsequent ipsilateral knee operations after their index multiligament knee reconstruction. Older age at surgery and female sex were associated with worse IKDC scores at follow-up. Despite the severity of the injuries in our cohort, we found high levels of patient-reported function and a high rate of successful RTS in the competitive athletes. Older age and female sex were associated with worse patient-reported knee function at follow-up.

Psychomatics-A Multidisciplinary Framework for Understanding Artificial Minds.

Although large language models (LLMs) and other artificial intelligence systems demonstrate cognitive skills similar to humans, such as concept learning and language acquisition, the way they process information fundamentally differs from biological cognition. To better understand these differences, this article introduces Psychomatics, a multidisciplinary framework bridging cognitive science, linguistics, and computer science. It aims to delve deeper into the high-level functioning of LLMs, focusing specifically on how LLMs acquire, learn, remember, and use information to produce their outputs. To achieve this goal, Psychomatics will rely on a comparative methodology, starting from a theory-driven research question-is the process of language development and use different in humans and LLMs?-drawing parallels between LLMs and biological systems. Our analysis shows how LLMs can map and manipulate complex linguistic patterns in their training data. Moreover, LLMs can follow Grice's Cooperative principle to provide relevant and informative responses. However, human cognition draws from multiple sources of meaning, including experiential, emotional, and imaginative facets, which transcend mere language processing and are rooted in our social and developmental trajectories. Moreover, current LLMs lack physical embodiment, reducing their ability to make sense of the intricate interplay between perception, action, and cognition that shapes human understanding and expression. Ultimately, Psychomatics holds the potential to yield transformative insights into the nature of language, cognition, and intelligence, both artificial and biological. Moreover, by drawing parallels between LLMs and human cognitive processes, Psychomatics can inform the development of more robust and human-like artificial intelligence systems.

Differences in palliative care needs between cancer patients and non-cancer patients at the start of specialized palliative care: A nationwide register-based study

Background: Patients with non-cancer disease are less likely to receive specialized palliative care than cancer patients. To be able to provide the best specialized palliative care, it is important to understand palliative care needs of non-cancer patients and whether the type and level of needs differ from those of cancer patients. Large studies including both cancer and non-cancer patients, using validated needs-assessment-tools, are needed to understand differences in palliative care needs at admittance to specialized palliative care. Aims: To compare palliative care needs at the start of palliative care for cancer and non-cancer disease. Design: Six-year nationwide register-based study. Setting/participants: This study included patients from all Danish specialized palliative care services (hospice care, hospital-based palliative care, home-based palliative care, or consultation) who completed a need-assessment-questionnaire. Ordinal logistic regression was performed to study the association between diagnosis and needs. Results: Cancer patients had a higher probability of receiving specialized palliative care. Of the 44,315 palliative care admissions included in this study, 93.3% were on cancer patients. Independent of diagnosis patients experienced on average six needs and high levels of fatigue and impaired physical functioning. Non-cancer patients had significantly higher odds of insomnia, fatigue and impaired emotional functioning, physical functioning, and quality of life whereas cancer patients had higher odds of pain (except for patients with neurological disease). Conclusions: The higher levels of several symptoms/problems among non-cancer patients compared to cancer patients suggests that referral to specialized palliative care should be improved for non-cancer patients perhaps by improving identification of palliative needs.

Evidence of Climate Change and the Conservation Needed to Halt the Further Deterioration of Small Glacial Lakes

Although somewhat debated, it is generally agreed in Europe that small water bodies comprise lentic ecosystems that are shallow (less than 20 m) and have a surface area of a few hectares (less than 10 ha). In Albania, 84 glacial lakes constitute a substantial portion of the aquatic ecosystems that sustain high levels of biodiversity, metabolic rates, and functionality. This paper discusses the integration of ecological sustainability into ecosystem services (i.e., cultural, regulatory, and sustaining services) and the national ecological networks of protected sites. This integration is particularly important in light of recent advancements regarding European integration. It is also important due to the catchment continuum, which addresses biodiversity values and gradients that, in this work, are considered using rotifer communities and aquatic plant species. The main causes of the stressors on small ecosystems are inappropriate land use, water pollution, altered habitats, non-native species introduction, resource mismanagement in basins, inadequate planning, and a lack of sector integration. The glacial lakes reflect climate change elements through: an increased number of dried glacial lakes, so only 84 remain functioning; the water level is slowly being reduced; the oscillation of the water level is steadily increasing; and the eutrophication process is rapidly advancing.

Arthroscopic Bone Block Stabilization for Anterior Shoulder Instability with Subcritical Glenohumeral Bone Loss.

The management options for anterior shoulder instability with minimal bone loss or with critical bone loss are well established. However, there is less clear evidence to guide management for patients with subcritical bone loss, the spectrum of pathology where soft tissue repair alone is prone to higher rates of failures. In this range of bone loss, likely around 13.5% to 20%, the goal of surgery is to restore function and stability while limiting morbidity. As with many procedures in the shoulder, this decision should be tailored to patient anatomy, functional goals, and risk factors. This article provides a review of our current understanding of subcritical bone loss and treatment strategies as well as innovations in management. While surgeons have largely understood that restoration of anatomy is important to optimize outcomes after stabilization surgery, there is increasing evidence that reconstructing bony anatomy and addressing both osseous and soft tissue structures yields better results than either alone. Even in the setting of subcritical bone loss, there is likely a benefit to combined osseous augmentation with soft tissue management. Additionally, there is new evidence to support management of even on-track humeral lesions when the distance to dislocation is sufficiently small, particularly for athletes. Surgeons must balance bony and soft tissue restoration to achieve optimal outcomes for anterior instability with subcritical bone loss. There are still significant limitations in the literature and several emerging techniques for management will require further study to prove their long-term efficacy. Beyond surgery, there should be a focus on a collaborative treatment strategy with the surgeon, patient, and therapists to achieve high-level function and minimize recurrence.

Altered Use of Context During Visual Perception in Psychotic Psychopathology: A Neurophysiological Investigation of Tuned and Untuned Suppression During Contrast Perception.

The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. To understand atypical surround suppression in psychotic psychopathology, we investigated neurophysiological responses in ISZ, healthy controls (HC), individuals with bipolar disorder (IBP), and first-degree relatives (ISZR/IBPR). Participants performed a contrast judgment task on a circular target with annular surrounds, with concurrent electroencephalography. Orientation-independent (untuned) suppression was estimated from responses to central targets with orthogonal surrounds; the orientation-dependence of suppression was estimated by fitting an exponential function to the increase in suppression as surrounds became more aligned with the center. ISZ exhibited weakened untuned suppression coupled with enhanced orientation-dependence of suppression. The N1 visual evoked potential was associated with the orientation-dependence of suppression, with ISZ and ISZR (but not IBP or IBPR) showing enhanced orientation-dependence of the N1. Collapsed across orientation conditions, the N1 for ISZ lacked asymmetry toward the right hemisphere; this reduction in N1 asymmetry was associated with reduced untuned suppression, real-world perceptual anomalies, and psychotic psychopathology. The overall amplitude of the N1 was reduced in ISZ and IBP. Key measures of symptomatology for ISZ are associated with reductions in untuned suppression. Increased sensitivity for ISZ to the relative orientation of suppressive surrounds is reflected in the N1 VEP, which is commonly associated with higher-level visual functions such as allocation of spatial attention or scene segmentation.

Epigenomic landscapes during prefrontal cortex development and aging in rhesus.

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

Concept Mapping as Problem-Based Learning: Assessing its Effectiveness in Teaching-Learning Processes

Whether they are students or working doctors, effective people in the medical field have knowledge structures that are made up of large, integrated frameworks of linked topics. Improving clinical problem- solving along with other higher-level cognitive functions is one of the many potential results of developing this knowledge foundation. Concept mapping is a technique that makes it possible to see how students conceptualise the ideas that constitute the basis of the knowledge they have been given. Concept maps are based on theories from the academic field of learning theory and may be used by students as a support aid when they solve problems (PBL). In problem-based learning (PBL) classrooms, students may draw concept maps that integrate fundamental scientific and social concepts in addition to PBL cases. In addition to promoting communication, detecting knowledge gaps, coming up with ideas for learning goals, stimulating application across disciplinary boundaries, and evaluating each student's progress, the usage of concept maps in PBL lessons may also be advantageous. Concept mapping may also be useful for students in other PBL contexts, such as large-scale seminar discussion and team-based learning settings. Students may get a deeper understanding of the relationships between different concepts and the Problem-Based Learning (PBL) case that is being examined by using these kinds of PBL settings. The creation of reliable, validity-evidenced tools is one of the challenges preventing idea mapping from being widely used in medical education.

Visual outcomes following bilateral implantation of a non-diffractive extended depth of focus toric intraocular lens using a mini-monovision approach.

To evaluate the clinical outcomes following bilateral implantation of the AcrySof™ IQ Vivity™ toric extended depth of focus (EDOF) intraocular lens (IOL). Prospective interventional case series. Patients with bilateral significant cataracts and pre-existing corneal astigmatism underwent cataract surgery and implantation with the AcrySof™ IQ Vivity™ toric IOL. Dominant eyes were targeted at emmetropia and non-dominant eyes at -0.50D. Primary endpoints were binocular uncorrected distance (UDVA), intermediate (UIVA at 66cm) and near (UNVA at 40cm) acuities at 3months. Secondary outcomes were corrected distance (CDVA), distance corrected intermediate (DCIVA) and distance corrected near (DCNVA), refractive predictability, rotational stability, binocular defocus curve, contrast sensitivity, Questionnaire for Visual Disturbances (QUVID) and Visual Function Index (VF-14) questionnaire scores. All visual acuities were converted to logarithm of minimum angle of resolution (logMAR) for analysis. 30 patients underwent uneventful phacoemulsification. The mean binocular UDVA, UIVA and UNVA were 0.06 ± 0.12, 0.11 ± 0.10 and 0.26 ± 0.10 respectively. The mean refractive spherical equivalent (MRSE) for dominant and non-dominant eyes were - 0.07D ± 0.27 and - 0.12D ± 0.54 respectively. 92.4% of dominant eyes and 84.6% of non-dominant eyes within 0.50D of target. The mean IOL rotation was 3.85° ± 5.09 with 86.7% of eyes with less than 5° of rotation. 26.7%, 20% and 36.7% of patients reported starbursts, haloes and glare respectively. The mean VF-14 score was 91.77. Bilateral implantation of the AcrySof™ IQ Vivity™ Toric IOL resulted in very good unaided visual acuities for far and intermediate distance with functional near vision. Dysphotopsias were reported but despite this, a high level of visual function was achieved.

Can International Classification of Functioning, Disability and Health (ICF) Be Used for Prediction of Work Capacity and Employment Status in Multiple Sclerosis?

Background: Multiple sclerosis (MS) affects many body functions and activities, including work capacity and ability to work. An evaluation of work-related parameters is important to understand the barriers to maintaining the job. The aim of this study was to evaluate if a Comprehensive International Classification of Functioning, Disability and Health (ICF) core set for MS can be used to predict work capacity and employment status. Methods: The cohort included 151 participants with MS (99 female/52 male, mean age 49 years) referred for a work capacity evaluation. Results: 71 (47.0%) were employed and a major part (131, 86.7%) had a work capacity between 20 and 40% with no difference between those who were employed and those who were unemployed. The analysis revealed that age and the following categories explained 68.8% of the work capacity: b770 Gait pattern functions; b730 Muscle power functions; b134 Sleep functions; d845 Acquiring, keeping and terminating a job; and b620 Urination functions. The following categories in 79.5% predicted ability to work: b164 Higher-level cognitive functions; d510 Washing oneself; d630; Preparing meals; and d870 Economic self-sufficiency. Conclusions: Here, we show that different functions/activities predicted work capacity in comparison with employment status in MS. Therefore, ICF should be implemented when assessing work ability.

PEMPS: a phylogenetic software tool to model the evolution of metabolic pathways

BackgroundMetabolic pathways support the enzyme flux that converts input chemicals into energy and cellular building blocks. With a constant rate of input, steady-state flux is achieved when metabolite concentrations and reaction rates remain constant over time. Individual genes undergo mutation, while selection acts on higher level functions of the pathway, such as steady-state flux where applicable. Modeling the evolution of metabolic pathways through mechanistic sets of ordinary differential equations is a piece of the genotype–phenotype map model for interpreting genetic variation and inter-specific differences. Such models can generate distinct compensatory changes and adaptive changes from directional selection, indicating single nucleotide polymorphisms and fixed differences that could affect phenotype. If used for inference, this would ultimately enable detection of selection on metabolic pathways as well as inference of ancestral states for metabolic pathway function.ResultsA software tool for simulating the evolution of metabolic pathways based upon underlying biochemistry, phylogenetics, and evolutionary considerations is presented. The Python program, Phylogenetic Evolution of Metabolic Pathway Simulator (PEMPS), implements a mutation-selection framework to simulate the evolution of the pathway over a phylogeny by interfacing with COPASI to calculate the steady-state flux of the metabolic network, introducing mutations as alterations in parameter values according to a model, and calculating a fitness score and corresponding probability of fixation based on the change in steady-state flux value(s). Results from simulations are consistent with a priori expectations of fixation probabilities and systematic change in model parameters.ConclusionsThe PEMPS program simulates the evolution of a metabolic pathway with a mutation-selection modeling framework based on criteria like steady-state flux that is designed to work with SBML-formatted kinetic models, and Newick-formatted phylogenetic trees. The Python software is run on the Linux command line and is available at https://github.com/nmccloskey/PEMPS.