An expert rule-based approach for identifying infantile-onset Pompe disease patients using retrospective electronic health records.

Pompe disease (OMIM #232300), a rare genetic disorder, leads to glycogen buildup in the body due to an enzyme deficiency, particularly harming the heart and muscles. Infantile-onset Pompe disease (IOPD) requires urgent treatment to prevent mortality, but the unavailability of these methods often delays diagnosis. Our study aims to streamline IOPD diagnosis in the UAE using electronic health records (EHRs) for faster, more accurate detection and timely treatment initiation. This study utilized electronic health records from the Abu Dhabi Healthcare Company (SEHA) healthcare network in the UAE to develop an expert rule-based screening approach operationalized through a dashboard. The study encompassed six diagnosed IOPD patients and screened 93,365 subjects. Expert rules were formulated to identify potential high-risk IOPD patients based on their age, particular symptoms, and creatine kinase levels. The proposed approach was evaluated using accuracy, sensitivity, and specificity. The proposed approach accurately identified five true positives, one false negative, and four false positive IOPD cases. The false negative case involved a patient with both Pompe disease and congenital heart disease. The focus on CHD led to the overlooking of Pompe disease, exacerbated by no measurement of creatine kinase. The false positive cases were diagnosed with Mitochondrial DNA depletion syndrome 12-A (SLC25A4 gene), Immunodeficiency-71 (ARPC1B mutation), Niemann-Pick disease type C (NPC1 gene mutation leading to frameshift), and Group B Streptococcus meningitis. The proposed approach of integrating expert rules with a dashboard facilitated efficient data visualization and automated patient screening, which aids in the early detection of Pompe disease. Future studies are encouraged to investigate the application of machine learning methodologies to enhance further the precision and efficiency of identifying patients with IOPD.

Predicting preterm birth using explainable machine learning in a prospective cohort of nulliparous and multiparous pregnant women.

Preterm birth (PTB) presents a complex challenge in pregnancy, often leading to significant perinatal and long-term morbidities. "While machine learning (ML) algorithms have shown promise in PTB prediction, the lack of interpretability in existing models hinders their clinical utility. This study aimed to predict PTB in a pregnant population using ML models, identify the key risk factors associated with PTB through the SHapley Additive exPlanations (SHAP) algorithm, and provide comprehensive explanations for these predictions to assist clinicians in providing appropriate care. This study analyzed a dataset of 3509 pregnant women in the United Arab Emirates and selected 35 risk factors associated with PTB based on the existing medical and artificial intelligence literature. Six ML algorithms were tested, wherein the XGBoost model exhibited the best performance, with an area under the operator receiving curves of 0.735 and 0.723 for parous and nulliparous women, respectively. The SHAP feature attribution framework was employed to identify the most significant risk factors linked to PTB. Additionally, individual patient analysis was performed using the SHAP and the local interpretable model-agnostic explanation algorithms (LIME). The overall incidence of PTB was 11.23% (11 and 12.1% in parous and nulliparous women, respectively). The main risk factors associated with PTB in parous women are previous PTB, previous cesarean section, preeclampsia during pregnancy, and maternal age. In nulliparous women, body mass index at delivery, maternal age, and the presence of amniotic infection were the most relevant risk factors. The trained ML prediction model developed in this study holds promise as a valuable screening tool for predicting PTB within this specific population. Furthermore, SHAP and LIME analyses can assist clinicians in understanding the individualized impact of each risk factor on their patients and provide appropriate care to reduce morbidity and mortality related to PTB.

Node embedding-based graph autoencoder outlier detection for adverse pregnancy outcomes.

Adverse pregnancy outcomes, such as low birth weight (LBW) and preterm birth (PTB), can have serious consequences for both the mother and infant. Early prediction of such outcomes is important for their prevention. Previous studies using traditional machine learning (ML) models for predicting PTB and LBW have encountered two important limitations: extreme class imbalance in medical datasets and the inability to account for complex relational structures between entities. To address these limitations, we propose a node embedding-based graph outlier detection algorithm to predict adverse pregnancy outcomes. We developed a knowledge graph using a well-curated representative dataset of the Emirati population and two node embedding algorithms. The graph autoencoder (GAE) was trained by applying a combination of original risk factors and node embedding features. Samples that were difficult to reconstruct at the output of GAE were identified as outliers considered representing PTB and LBW samples. Our experiments using LBW, PTB, and very PTB datasets demonstrated that incorporating node embedding considerably improved performance, achieving a 12% higher AUC-ROC compared to traditional GAE. Our study demonstrates the effectiveness of node embedding and graph outlier detection in improving the prediction performance of adverse pregnancy outcomes in well-curated population datasets.

Deep Multi-Magnification Similarity Learning for Histopathological Image Classification.

Precise classification of histopathological images is crucial to computer-aided diagnosis in clinical practice. Magnification-based learning networks have attracted considerable attention for their ability to improve performance in histopathological classification. However, the fusion of pyramids of histopathological images at different magnifications is an under-explored area. In this paper, we proposed a novel deep multi-magnification similarity learning (DSML) approach that can be useful for the interpretation of multi-magnification learning framework and easy to visualize feature representation from low-dimension (e.g., cell-level) to high-dimension (e.g., tissue-level), which has overcome the difficulty of understanding cross-magnification information propagation. It uses a similarity cross entropy loss function designation to simultaneously learn the similarity of the information among cross-magnifications. In order to verify the effectiveness of DMSL, experiments with different network backbones and different magnification combinations were designed, and its ability to interpret was also investigated through visualization. Our experiments were performed on two different histopathological datasets: a clinical nasopharyngeal carcinoma and a public breast cancer BCSS2021 dataset. The results show that our method achieved outstanding performance in classification with a higher value of area under curve, accuracy, and F-score than other comparable methods. Moreover, the reasons behind multi-magnification effectiveness were discussed.

Infant Low Birth Weight Prediction Using Graph Embedding Features.

Low Birth weight (LBW) infants pose a serious public health concern worldwide in both the short and long term for infants and their mothers. Infant weight prediction prior to birth can help to identify risk factors and reduce the risk of infant morbidity and mortality. Although many Machine Learning (ML) algorithms have been proposed for LBW prediction using maternal features and produced considerable model performance, their performance needs to be improved so that they can be adapted in real-world clinical settings. Existing algorithms used for LBW classification often fail to capture structural information from the tabular dataset of patients with different complications. Therefore, to improve the LBW classification performance, we propose a solution by transforming the tabular data into a knowledge graph with the aim that patients from the same class (normal or LBW) exhibit similar patterns in the graphs. To achieve this, several features related to each node are extracted such as node embedding using node2vec algorithm, node degree, node similarity, nearest neighbors, etc. Our method is evaluated on a real-life dataset obtained from a large cohort study in the United Arab Emirates which contains data from 3453 patients. Multiple experiments were performed using the seven most commonly used ML models on the original dataset, graph features, and a combination of features, respectively. Experimental results show that our proposed method achieved the best performance with an area under the curve of 0.834 which is over 6% improvement compared to using the original risk factors without transforming them into knowledge graphs. Furthermore, we provide the clinical relevance of the proposed model that are important for the model to be adapted in clinical settings.

Deep Learning-Based Automatic Assessment of Lung Impairment in COVID-19 Pneumonia: Predicting Markers of Hypoxia With Computer Vision.

Background: Hypoxia is a potentially life-threatening condition that can be seen in pneumonia patients. Objective: We aimed to develop and test an automatic assessment of lung impairment in COVID-19 associated pneumonia with machine learning regression models that predict markers of respiratory and cardiovascular functioning from radiograms and lung CT. Materials and Methods: We enrolled a total of 605 COVID-19 cases admitted to Al Ain Hospital from 24 February to 1 July 2020 into the study. The inclusion criteria were as follows: age ≥ 18 years; inpatient admission; PCR positive for SARS-CoV-2; lung CT available at PACS. We designed a CNN-based regression model to predict systemic oxygenation markers from lung CT and 2D diagnostic images of the chest. The 2D images generated by averaging CT scans were analogous to the frontal and lateral view radiograms. The functional (heart and breath rate, blood pressure) and biochemical findings (SpO2, H C O 3 - , K +, Na +, anion gap, C-reactive protein) served as ground truth. Results: Radiologic findings in the lungs of COVID-19 patients provide reliable assessments of functional status with clinical utility. If fed to ML models, the sagittal view radiograms reflect dyspnea more accurately than the coronal view radiograms due to the smaller size and the lower model complexity. Mean absolute error of the models trained on single-projection radiograms was approximately 11÷12% and it dropped by 0.5÷1% if both projections were used (11.97 ± 9.23 vs. 11.43 ± 7.51%; p = 0.70). Thus, the ML regression models based on 2D images acquired in multiple planes had slightly better performance. The data blending approach was as efficient as the voting regression technique: 10.90 ± 6.72 vs. 11.96 ± 8.30%, p = 0.94. The models trained on 3D images were more accurate than those on 2D: 8.27 ± 4.13 and 11.75 ± 8.26%, p = 0.14 before lung extraction; 10.66 ± 5.83 and 7.94 ± 4.13%, p = 0.18 after the extraction. The lung extraction boosts 3D model performance unsubstantially (from 8.27 ± 4.13 to 7.94 ± 4.13%; p = 0.82). However, none of the differences between 3D and 2D were statistically significant. Conclusion: The constructed ML algorithms can serve as models of structure-function association and pathophysiologic changes in COVID-19. The algorithms can improve risk evaluation and disease management especially after oxygen therapy that changes functional findings. Thus, the structural assessment of acute lung injury speaks of disease severity.

A Biofeedback-Based Mobile App With Serious Games for Young Adults With Anxiety in the United Arab Emirates: Development and Usability Study.

BACKGROUND: Following the outbreak of COVID-19, several studies have reported that young adults encountered a rise in anxiety symptoms, which could negatively affect their quality of life. Promising evidence suggests that mobile apps with biofeedback, serious games, breathing exercises, and positive messaging, among other features, are useful for anxiety self-management and treatment. OBJECTIVE: This study aimed to develop and evaluate the usability of a biofeedback-based app with serious games for young adults with anxiety in the United Arab Emirates (UAE). METHODS: This study consists of two phases: Phase I describes the design and development of the app, while Phase II presents the results of a usability evaluation by experts. To elicit the app's requirements during Phase I, we conducted (1) a survey to investigate preferences of young adults in the UAE for mobile games for stress relief; (2) an analysis of serious games for anxiety; and (3) interviews with mental health professionals and young adults in the UAE. In Phase II, five experts tested the usability of the developed app using a set of Nielsen's usability heuristics. RESULTS: A fully functional biofeedback-based app with serious games was co-designed with mental health professionals. The app included 4 games (ie, a biofeedback game, card game, arcade game, and memory game), 2 relaxation techniques (ie, a breathing exercise and yoga videos), and 2 additional features (ie, positive messaging and a mood tracking calendar). The results of Phase II showed that the developed app is efficient, simple, and easy to use. Overall, the app design scored an average of 4 out of 5. CONCLUSIONS: The elicitation techniques used in Phase I resulted in the development of an easy-to-use app for the self-management of anxiety. Further research is required to determine the app's usability and effectiveness in the target population.

Infant birth weight estimation and low birth weight classification in United Arab Emirates using machine learning algorithms.

Accurate prediction of a newborn's birth weight (BW) is a crucial determinant to evaluate the newborn's health and safety. Infants with low BW (LBW) are at a higher risk of serious short- and long-term health outcomes. Over the past decade, machine learning (ML) techniques have shown a successful breakthrough in the field of medical diagnostics. Various automated systems have been proposed that use maternal features for LBW prediction. However, each proposed system uses different maternal features for LBW classification and estimation. Therefore, this paper provides a detailed setup for BW estimation and LBW classification. Multiple subsets of features were combined to perform predictions with and without feature selection techniques. Furthermore, the synthetic minority oversampling technique was employed to oversample the minority class. The performance of 30 ML algorithms was evaluated for both infant BW estimation and LBW classification. Experiments were performed on a self-created dataset with 88 features. The dataset was obtained from 821 women from three hospitals in the United Arab Emirates. Different performance metrics, such as mean absolute error and mean absolute percent error, were used for BW estimation. Accuracy, precision, recall, F-scores, and confusion matrices were used for LBW classification. Extensive experiments performed using five-folds cross validation show that the best weight estimation was obtained using Random Forest algorithm with mean absolute error of 294.53 g while the best classification performance was obtained using Logistic Regression with SMOTE oversampling techniques that achieved accuracy, precision, recall and F1 score of 90.24%, 87.6%, 90.2% and 0.89, respectively. The results also suggest that features such as diabetes, hypertension, and gestational age, play a vital role in LBW classification.

Utilization of social media in floods assessment using data mining techniques.

Floods are among the devastating types of disasters in terms of human life, social and financial losses. Authoritative data from flood gauges are scarce in arid regions because of the specific type of dry climate that dysfunctions these measuring devices. Hence, social media data could be a useful tool in this case, where a wealth of information is available online. This study investigates the reliability of flood related data quality collected from social media, particularly for an arid region where the usage of flow gauges is limited. The data (text, images and videos) of social media, related to a flood event, was analyzed using the Machine Learning approach. For this reason, digital data (758 images and 1413 video frames) was converted into numeric values through ResNet50 model using the VGG-16 architecture. Numeric data of images, videos and text was further classified using different Machine Learning algorithms. Receiver operating characteristics (ROC) curve and area under curve (AUC) methods were used to evaluate and compare the performance of the developed machine learning algorithms. This novel approach of studying the quality of social media data could be a reliable alternative in the absence of real-time flow gauges data. A flash flood that occurred in the United Arab Emirates (UAE) from March 7-11, 2016 was selected as the focus of this study. Random forest showed the highest accuracy of 80.18% among the five other classifiers for images and videos. Precipitation/rainfall data were used to validate social media data, which showed a significant relationship between rainfall and the number of posts. The validity of the machine learning models was assessed using the area under the curve, precision-recall curve, root mean square error, and kappa statistics to confirm the validity and accuracy of the model. The data quality of YouTube videos was found to have the highest accuracy followed by Facebook, Flickr, Twitter, and Instagram. These results showed that social media data could be used when gauge data is unavailable.

Proportional Changes in Cognitive Subdomains During Normal Brain Aging.

Background: Neuroscience lacks a reliable method of screening the early stages of dementia. Objective: To improve the diagnostics of age-related cognitive functions by developing insight into the proportionality of age-related changes in cognitive subdomains. Materials and Methods: We composed a battery of psychophysiological tests and collected an open-access psychophysiological outcomes of brain atrophy (POBA) dataset by testing individuals without dementia. To extend the utility of machine learning (ML) classification in cognitive studies, we proposed estimates of the disproportional changes in cognitive functions: an index of simple reaction time to decision-making time (ISD), ISD with the accuracy performance (ISDA), and an index of performance in simple and complex visual-motor reaction with account for accuracy (ISCA). Studying the distribution of the values of the indices over age allowed us to verify whether diverse cognitive functions decline equally throughout life or there is a divergence in age-related cognitive changes. Results: Unsupervised ML clustering shows that the optimal number of homogeneous age groups is four. The sample is segregated into the following age-groups: Adolescents ∈ [0, 20), Young adults ∈ [20, 40), Midlife adults ∈ [40, 60) and Older adults ≥60 year of age. For ISD, ISDA, and ISCA values, only the median of the Adolescents group is different from that of the other three age-groups sharing a similar distribution pattern (p > 0.01). After neurodevelopment and maturation, the indices preserve almost constant values with a slight trend toward functional decline. The reaction to a moving object (RMO) test results (RMO_mean) follow another tendency. The Midlife adults group's median significantly differs from the remaining three age subsamples (p < 0.01). No general trend in age-related changes of this dependent variable is observed. For all the data (ISD, ISDA, ISCA, and RMO_mean), Levene's test reveals no significant changes of the variances in age-groups (p > 0.05). Homoscedasticity also supports our assumption about a linear dependency between the observed features and age. Conclusion: In healthy brain aging, there are proportional age-related changes in the time estimates of information processing speed and inhibitory control in task switching. Future studies should test patients with dementia to determine whether the changes of the aforementioned indicators follow different patterns.

Predicting Age From Behavioral Test Performance for Screening Early Onset of Cognitive Decline.

Background: Neuronal reactions and cognitive processes slow down during aging. The onset, rate, and extent of changes vary considerably from individual to individual. Assessing the changes throughout the lifespan is a challenging task. No existing test covers all domains, and batteries of tests are administered. The best strategy is to study each functional domain separately by applying different behavioral tasks whereby the tests reflect the conceptual structure of cognition. Such an approach has limitations that are described in the article. Objective: Our aim was to improve the diagnosis of early cognitive decline. We estimated the onset of cognitive decline in a healthy population, using behavioral tests, and predicted the age group of an individual. The comparison between the predicted ("cognitive") and chronological age will contribute to the early diagnosis of accelerated aging. Materials and Methods: We used publicly available datasets (POBA, SSCT) and Pearson correlation coefficients to assess the relationship between age and tests results, Kruskal-Wallis test to compare distribution, clustering methods to find an onset of cognitive decline, feature selection to enhance performance of the clustering algorithms, and classification methods to predict an age group from cognitive tests results. Results: The major results of the psychophysiological tests followed a U-shape function across the lifespan, which reflected the known inverted function of white matter volume changes. Optimal values were observed in those aged over 35 years, with a period of stability and accelerated decline after 55-60 years of age. The shape of the age-related variance of the performance of major cognitive tests was linear, which followed the trend of lifespan gray matter volume changes starting from adolescence. There was no significant sex difference in lifelong dynamics of major tests estimates. The performance of the classification model for identifying subject age groups was high. Conclusions: ML models can be designed and utilized as computer-aided detectors of neurocognitive decline. Our study demonstrated great promise for the utility of classification models to predict age-related changes. These findings encourage further explorations combining several tests from the cognitive and psychophysiological test battery to derive the most reliable set of tests toward the development of a highly-accurate ML model.

The estimations of the COVID-19 incubation period: A scoping reviews of the literature.

BACKGROUND: A novel coronavirus (COVID-19) has taken the world by storm. The disease has spread very swiftly worldwide. A timely clue which includes the estimation of the incubation period among COVID-19 patients can allow governments and healthcare authorities to act accordingly. OBJECTIVES: to undertake a review and critical appraisal of all published/preprint reports that offer an estimation of incubation periods for COVID-19. ELIGIBILITY CRITERIA: This research looked for all relevant published articles between the dates of December 1, 2019, and April 25, 2020, i.e. those that were related to the COVID-19 incubation period. Papers were included if they were written in English, and involved human participants. Papers were excluded if they were not original (e.g. reviews, editorials, letters, commentaries, or duplications). SOURCES OF EVIDENCE: COVID-19 Open Research Dataset supplied by Georgetown's Centre for Security and Emerging Technology as well as PubMed and Embase via Arxiv, medRxiv, and bioRxiv. CHARTING METHODS: A data-charting form was jointly developed by the two reviewers (NZ and EA), to determine which variables to extract. The two reviewers independently charted the data, discussed the results, and updated the data-charting form. RESULTS AND CONCLUSIONS: Screening was undertaken 44,000 articles with a final selection of 25 studies referring to 18 different experimental projects related to the estimation of the incubation period of COVID-19. The majority of extant published estimates offer empirical evidence showing that the incubation period for the virus is a mean of 7.8 days, with a median of 5.01 days, which falls into the ranges proposed by the WHO (0-14 days) and the ECDC (2-12 days). Nevertheless, a number of authors proposed that quarantine time should be a minimum of 14 days and that for estimates of mortality risks a median time delay of 13 days between illness and mortality should be under consideration. It is unclear as to whether any correlation exists between the age of patients and the length of time they incubate the virus.

Prediction of COVID-19 severity using laboratory findings on admission: informative values, thresholds, ML model performance.

BACKGROUND: Despite the necessity, there is no reliable biomarker to predict disease severity and prognosis of patients with COVID-19. The currently published prediction models are not fully applicable to clinical use. OBJECTIVES: To identify predictive biomarkers of COVID-19 severity and to justify their threshold values for the stratification of the risk of deterioration that would require transferring to the intensive care unit (ICU). METHODS: The study cohort (560 subjects) included all consecutive patients admitted to Dubai Mediclinic Parkview Hospital from February to May 2020 with COVID-19 confirmed by the PCR. The challenge of finding the cut-off thresholds was the unbalanced dataset (eg, the disproportion in the number of 72 patients admitted to ICU vs 488 non-severe cases). Therefore, we customised supervised machine learning (ML) algorithm in terms of threshold value used to predict worsening. RESULTS: With the default thresholds returned by the ML estimator, the performance of the models was low. It was improved by setting the cut-off level to the 25th percentile for lymphocyte count and the 75th percentile for other features. The study justified the following threshold values of the laboratory tests done on admission: lymphocyte count <2.59×109/L, and the upper levels for total bilirubin 11.9 µmol/L, alanine aminotransferase 43 U/L, aspartate aminotransferase 32 U/L, D-dimer 0.7 mg/L, activated partial thromboplastin time (aPTT) 39.9 s, creatine kinase 247 U/L, C reactive protein (CRP) 14.3 mg/L, lactate dehydrogenase 246 U/L, troponin 0.037 ng/mL, ferritin 498 ng/mL and fibrinogen 446 mg/dL. CONCLUSION: The performance of the neural network trained with top valuable tests (aPTT, CRP and fibrinogen) is admissible (area under the curve (AUC) 0.86; 95% CI 0.486 to 0.884; p<0.001) and comparable with the model trained with all the tests (AUC 0.90; 95% CI 0.812 to 0.902; p<0.001). Free online tool at https://med-predict.com illustrates the study results.

Ethnicity-Specific Features of COVID-19 Among Arabs, Africans, South Asians, East Asians, and Caucasians in the United Arab Emirates.

Background: Dubai (United Arab Emirates; UAE) has a multi-national population which makes it exceptionally interesting study sample because of its unique demographic factors. Objective: To stratify the risk factors for the multinational society of the UAE. Methods: A retrospective chart review of 560 patients sequentially admitted to inpatient care with laboratory confirmed COVID-19 was conducted. We studied patients' demographics, clinical features, laboratory results, disease severity, and outcomes. The parameters were compared across different ethnic groups using tree-based estimators to rank the ethnicity-specific disease features. We trained ML classification algorithms to build a model of ethnic specificity of COVID-19 based on clinical presentation and laboratory findings on admission. Results: Out of 560 patients, 43.6% were South Asians, 26.4% Middle Easterns, 16.8% East Asians, 10.7% Caucasians, and 2.5% are under others. UAE nationals represented half of the Middle Eastern patients, and 13% of the entire cohort. Hypertension was the most common comorbidity in COVID-19 patients. Subjective complaint of fever and cough were the chief presenting symptoms. Two-thirds of the patients had either a mild disease or were asymptomatic. Only 20% of the entire cohort needed oxygen therapy, and 12% needed ICU admission. Forty patients (~7%) needed invasive ventilation and fifteen patients died (2.7%). We observed differences in disease severity among different ethnic groups. Caucasian or East-Asian COVID-19 patients tended to have a more severe disease despite a lower risk profile. In contrast to this, Middle Eastern COVID-19 patients had a higher risk factor profile, but they did not differ markedly in disease severity from the other ethnic groups. There was no noticeable difference between the Middle Eastern subethnicities-Arabs and Africans-in disease severity (p = 0.81). However, there were disparities in the SOFA score, D-dimer (p = 0.015), fibrinogen (p = 0.007), and background diseases (hypertension, p = 0.003; diabetes and smoking, p = 0.045) between the subethnicities. Conclusion: We observed variations in disease severity among different ethnic groups. The high accuracy (average AUC = 0.9586) of the ethnicity classification model based on the laboratory and clinical findings suggests the presence of ethnic-specific disease features. Larger studies are needed to explore the role of ethnicity in COVID-19 disease features.

Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes.

BACKGROUND: The human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one. OBJECTIVE: To work out a descriptive model of brain structural and functional changes in normal aging. MATERIALS AND METHODS: By using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U-test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T-test. RESULTS: White matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age. CONCLUSION: The article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results.

Applying the Inverse Efficiency Score to Visual-Motor Task for Studying Speed-Accuracy Performance While Aging.

Background: The current study examines the relationship between speed and accuracy of performance in a reaction time setting and explores the informative value of the inverse efficiency score (IES) regarding the possibility to reflect age-related cognitive changes. Objectives: To study the characteristics of speed and accuracy while performing psychophysiological tests throughout the lifespan; to examine the speed-accuracy ratio in age groups and to apply IES to discriminative visual-motor reaction task; and to figure out the predictive potential of psychophysiological tests to identify IES values. Methods: We utilize nonparametric statistical tests, regression analysis, and supervised machine learning methods. Results and Conclusion: The examinees under 20 and over 60 years of age share one tendency regarding the speed-accuracy ratio without speed-accuracy trade-off. Both at the time of active developmental changes in adolescence and during ongoing atrophic changes in elderly there is a tendency toward a rise of the number of mistakes while slowing the reaction. In the age range from 20 to 60 the relationship between the speed and accuracy is opposite and speed-accuracy trade-off is present. In our battery, complex visual-motor reaction is the only test with the significant negative association between reaction time and error rate in the subcohort of young and midlife adults taken together. On average, women perform more slowly and accurately than men in the speed-accuracy task, however most of the gender-related differences are insignificant. Using results of other psychophysiological tests, we predicted IES values for the visual-motor reaction with high accuracy (R 2 = 0.77 ± 0.08; mean absolute error / IES range = 3.37%). The regression model shows the best performance in the cognitively preserved population groups of young and middle-aged adults (20-60 years). Because of the individual rate of neurodevelopment in youth and cognitive decline in the elderly, the regression model for these subcohorts has a low predictive performance. IES accounts for different cognitive subdomains and may reflect their disproportional changes throughout the lifespan. This encourages us to proceed to explore the combination of executive functioning and psychophysiological test results utilizing machine learning models. The latter can be designed as a reliable computer-aided detector of cognitive changes at early stages.

Global and Temporal COVID-19 Risk Evaluation.

The COVID-19 pandemic has caused unprecedented crisis across the world, with many countries struggling with the pandemic. In order to understand how each country is impacted by the virus and assess the risk on a global scale we present a regression based analysis using two pre-existing indexes, namely the Inform and Infectious Disease Vulnerability Index, in conjunction with the number of elderly living in the population. Further we introduce a temporal layer in our modeling by incorporating the stringency level employed by each country over a period of 6 time intervals. Our results show that the indexes and level of stringency are not ideally suited for explaining variation in COVID-19 risk, however the ratio of elderly in the population is a stand out indicator in terms of its predictive power for mortality risk. In conclusion, we discuss how such modeling approaches can assist public health policy.

Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review.

BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. "Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.

Blockchains for Secure Digitized Medicine.

Blockchain as an emerging technology has been gaining in popularity, with more possible applications to utilize the technology in the near future. With the offer of a decentralized, distributed environment without the need for a third trusted party (TTP), blockchains are being used to solve issues in systems that are susceptible to cyberattacks. One possible field that could benefit from blockchains that researchers have been focusing on is healthcare. Current healthcare information systems face several challenges, such as fragmented patient data, centralized systems which are viewed as single points of attacks, and the lack of patient-oriented services. In this paper, we investigate and analyze recent literature related to the use of blockchains to tackle issues found in modern healthcare information systems. This is done to understand issues that researchers commonly focus on, to discover remaining areas of concern in any proposed solution, and to understand the possible directions of the integration of blockchains in healthcare and personalized medicine. Background information regarding blockchains and existing healthcare information systems is reviewed, followed by the methodology used in the preparation of this review, where the research questions to consider are stated. Afterwards, an analysis of the results is provided, concluding with a discussion of the remaining issues that need to be focused on, and how blockchains could benefit the healthcare sector and empower personalized medicine.

Computational investigation of mechanistic insights of Aß42 interactions against extracellular domain of nAChRα7 in Alzheimer's disease.

AIM: Amyloid beta (Aß) 1-42, which is a basic constituent of amyloid plaques, binds with extracellular transmembrane receptor nicotine acetylcholine receptor α7 (nAChRα7) in Alzheimer's disease. MATERIALS AND METHODS: In the current study, a computational approach was employed to explore the active binding sites of nAChRα7 through Aß 1-42 interactions and their involvement in the activation of downstream signalling pathways. Sequential and structural analyses were performed on the extracellular part of nAChRα7 to identify its core active binding site. RESULTS: Results showed that a conserved residual pattern and well superimposed structures were observed in all nAChRs proteins. Molecular docking servers were used to predict the common interactive residues in nAChRα7 and Aß1-42 proteins. The docking profile results showed some common interactive residues such as Glu22, Ala42 and Trp171 may consider as the active key player in the activation of downstream signalling pathways. Moreover, the signal communication and receiving efficacy of best-docked complexes was checked through DynOmic online server. Furthermore, the results from molecular dynamic simulation experiment showed the stability of nAChRα7. The generated root mean square deviations and fluctuations (RMSD/F), solvent accessible surface area (SASA) and radius of gyration (Rg) graphs of nAChRα7 also showed its backbone stability and compactness, respectively. CONCLUSION: Taken together, our predicted results intimated the structural insight on the molecular interactions of beta amyloid protein involved in the activation of nAChRα7 receptor. In future, a better understanding of nAChRα7 and their interconnected proteins signalling cascade may be consider as target to cure Alzheimer's disease.