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.

Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer's disease by evaluating protein interactions through molecular docking and dynamic simulations.

Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer's disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer's disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer's disease by inhibiting the protein tyrosine kinase 2 pathway.

BioCarian: search engine for exploratory searches in heterogeneous biological databases.

BACKGROUND: There are a large number of biological databases publicly available for scientists in the web. Also, there are many private databases generated in the course of research projects. These databases are in a wide variety of formats. Web standards have evolved in the recent times and semantic web technologies are now available to interconnect diverse and heterogeneous sources of data. Therefore, integration and querying of biological databases can be facilitated by techniques used in semantic web. Heterogeneous databases can be converted into Resource Description Format (RDF) and queried using SPARQL language. Searching for exact queries in these databases is trivial. However, exploratory searches need customized solutions, especially when multiple databases are involved. This process is cumbersome and time consuming for those without a sufficient background in computer science. In this context, a search engine facilitating exploratory searches of databases would be of great help to the scientific community. RESULTS: We present BioCarian, an efficient and user-friendly search engine for performing exploratory searches on biological databases. The search engine is an interface for SPARQL queries over RDF databases. We note that many of the databases can be converted to tabular form. We first convert the tabular databases to RDF. The search engine provides a graphical interface based on facets to explore the converted databases. The facet interface is more advanced than conventional facets. It allows complex queries to be constructed, and have additional features like ranking of facet values based on several criteria, visually indicating the relevance of a facet value and presenting the most important facet values when a large number of choices are available. For the advanced users, SPARQL queries can be run directly on the databases. Using this feature, users will be able to incorporate federated searches of SPARQL endpoints. We used the search engine to do an exploratory search on previously published viral integration data and were able to deduce the main conclusions of the original publication. BioCarian is accessible via http://www.biocarian.com . CONCLUSIONS: We have developed a search engine to explore RDF databases that can be used by both novice and advanced users.

Detecting protein complexes in protein interaction networks using a ranking algorithm with a refined merging procedure.

BACKGROUND: Developing suitable methods for the identification of protein complexes remains an active research area. It is important since it allows better understanding of cellular functions as well as malfunctions and it consequently leads to producing more effective cures for diseases. In this context, various computational approaches were introduced to complement high-throughput experimental methods which typically involve large datasets, are expensive in terms of time and cost, and are usually subject to spurious interactions. RESULTS: In this paper, we propose ProRank+, a method which detects protein complexes in protein interaction networks. The presented approach is mainly based on a ranking algorithm which sorts proteins according to their importance in the interaction network, and a merging procedure which refines the detected complexes in terms of their protein members. ProRank + was compared to several state-of-the-art approaches in order to show its effectiveness. It was able to detect more protein complexes with higher quality scores. CONCLUSIONS: The experimental results achieved by ProRank + show its ability to detect protein complexes in protein interaction networks. Eventually, the method could potentially identify previously-undiscovered protein complexes.The datasets and source codes are freely available for academic purposes at http://faculty.uaeu.ac.ae/nzaki/Research.htm.

Protein inter-domain linker prediction using Random Forest and amino acid physiochemical properties.

BACKGROUND: Protein chains are generally long and consist of multiple domains. Domains are distinct structural units of a protein that can evolve and function independently. The accurate prediction of protein domain linkers and boundaries is often regarded as the initial step of protein tertiary structure and function predictions. Such information not only enhances protein-targeted drug development but also reduces the experimental cost of protein analysis by allowing researchers to work on a set of smaller and independent units. In this study, we propose a novel and accurate domain-linker prediction approach based on protein primary structure information only. We utilize a nature-inspired machine-learning model called Random Forest along with a novel domain-linker profile that contains physiochemical and domain-linker information of amino acid sequences. RESULTS: The proposed approach was tested on two well-known benchmark protein datasets and achieved 68% sensitivity and 99% precision, which is better than any existing protein domain-linker predictor. Without applying any data balancing technique such as class weighting and data re-sampling, the proposed approach is able to accurately classify inter-domain linkers from highly imbalanced datasets. CONCLUSION: Our experimental results prove that the proposed approach is useful for domain-linker identification in highly imbalanced single- and multi-domain proteins.

Protein complex detection using interaction reliability assessment and weighted clustering coefficient.

BACKGROUND: Predicting protein complexes from protein-protein interaction data is becoming a fundamental problem in computational biology. The identification and characterization of protein complexes implicated are crucial to the understanding of the molecular events under normal and abnormal physiological conditions. On the other hand, large datasets of experimentally detected protein-protein interactions were determined using High-throughput experimental techniques. However, experimental data is usually liable to contain a large number of spurious interactions. Therefore, it is essential to validate these interactions before exploiting them to predict protein complexes. RESULTS: In this paper, we propose a novel graph mining algorithm (PEWCC) to identify such protein complexes. Firstly, the algorithm assesses the reliability of the interaction data, then predicts protein complexes based on the concept of weighted clustering coefficient. To demonstrate the effectiveness of the proposed method, the performance of PEWCC was compared to several methods. PEWCC was able to detect more matched complexes than any of the state-of-the-art methods with higher quality scores. CONCLUSIONS: The higher accuracy achieved by PEWCC in detecting protein complexes is a valid argument in favor of the proposed method. The datasets and programs are freely available at http://faculty.uaeu.ac.ae/nzaki/Research.htm.

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.

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.

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.

Detection of protein complexes using a protein ranking algorithm.

Detecting protein complexes from protein-protein interaction (PPI) network is becoming a difficult challenge in computational biology. There is ample evidence that many disease mechanisms involve protein complexes, and being able to predict these complexes is important to the characterization of the relevant disease for diagnostic and treatment purposes. This article introduces a novel method for detecting protein complexes from PPI by using a protein ranking algorithm (ProRank). ProRank quantifies the importance of each protein based on the interaction structure and the evolutionarily relationships between proteins in the network. A novel way of identifying essential proteins which are known for their critical role in mediating cellular processes and constructing protein complexes is proposed and analyzed. We evaluate the performance of ProRank using two PPI networks on two reference sets of protein complexes created from Munich Information Center for Protein Sequence, containing 81 and 162 known complexes, respectively. We compare the performance of ProRank to some of the well known protein complex prediction methods (ClusterONE, CMC, CFinder, MCL, MCode and Core) in terms of precision and recall. We show that ProRank predicts more complexes correctly at a competitive level of precision and recall. The level of the accuracy achieved using ProRank in comparison to other recent methods for detecting protein complexes is a strong argument in favor of the proposed method.

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.

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.

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.

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.

Conotoxin protein classification using free scores of words and support vector machines.

BACKGROUND: Conotoxin has been proven to be effective in drug design and could be used to treat various disorders such as schizophrenia, neuromuscular disorders and chronic pain. With the rapidly growing interest in conotoxin, accurate conotoxin superfamily classification tools are desirable to systematize the increasing number of newly discovered sequences and structures. However, despite the significance and extensive experimental investigations on conotoxin, those tools have not been intensively explored. RESULTS: In this paper, we propose to consider suboptimal alignments of words with restricted length. We developed a scoring system based on local alignment partition functions, called free score. The scoring system plays the key role in the feature extraction step of support vector machine classification. In the classification of conotoxin proteins, our method, SVM-Freescore, features an improved sensitivity and specificity by approximately 5.864% and 3.76%, respectively, over previously reported methods. For the generalization purpose, SVM-Freescore was also applied to classify superfamilies from curated and high quality database such as ConoServer. The average computed sensitivity and specificity for the superfamily classification were found to be 0.9742 and 0.9917, respectively. CONCLUSIONS: The SVM-Freescore method is shown to be a useful sequence-based analysis tool for functional and structural characterization of conotoxin proteins. The datasets and the software are available at http://faculty.uaeu.ac.ae/nzaki/SVM-Freescore.htm.

Strike: a protein-protein interaction classification approach.

Protein-protein interaction has proven to be a valuable biological knowledge and an initial point for understanding how the cell internally works. In this chapter, we introduce a novel approach termed STRIKE which uses String Kernel to predict protein-protein interaction. STRIKE classifies protein pairs into "interacting" and "non-interacting" sets based solely on amino acid sequence information. The classification is performed by applying the string kernel approach, which has been shown to achieve good performance on text categorization and protein sequence classification. Two proteins are classified as "interacting" if they contain similar substrings of amino acids. Strings' similarity would allow one to infer homology which could lead to a very similar structural relationship. To evaluate the performance of STRIKE, we apply it to classify into "interacting" and "non-interacting" protein pairs. The dataset of the protein pairs are generated from the yeast protein interaction literature. The dataset is supported by different lines of experimental evidence. STRIKE was able to achieve reasonable improvement over the existing protein-protein interaction prediction methods.

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.

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.