Functional characterization and structural prediction of hypothetical proteins in monkeypox virus and identification of potential inhibitors.

The excessive activation of the monkeypox virus (MPXV-Congo_8-156) is linked to various skin and respiratory disorders such as rashes, fluid-filled blisters, swollen lymph nodes and encephalitis (inflammation of the brain), highlighting MPXV-Congo_8-156 as a promising target for drug intervention. Despite the effectiveness of Cidofovir, in inhibiting MPXV activity, its limited ability to penetrate the skin and its strong side effects restrict its application. To address this challenge, we screened 500 compounds capable of penetrating the skin and gastrointestinal tract to identify potent MPXV inhibitors. Various characterization schemes and structural models of MPXV-Congo_8-156 were explored with bioinformatics tools like PROTPARAM, SOPMA, SWISS-MODEL and PROCHECK. Using molecular docking in PyRx, we evaluated the binding affinities of these compounds with MPXV-Congo_8-156 and identified the top five candidates ranging from - 9.2 to - 8.8 kcal/mol. ADMET analysis indicated that all five compounds were safer alternatives, showing no AMES toxicity or carcinogenicity in toxicological assessments. Molecular dynamics (MD) simulations, conducted for 100 ns each, confirmed the docking interactions of the top five compounds alongside the control (Cidofovir), validating their potential as MPXV inhibitors. The compounds with PubChem CID numbers 4061636, 4422538, 3583576, 4856107 and 4800629 demonstrated strong support in terms of root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) value, hydrogen bond analysis, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. Thus, our investigation identified these five compounds as promising inhibitors of MPXV, offering potential therapeutic avenues. However, further in vivo studies are necessary to validate our findings.

Performance investigation of epilepsy detection from noisy EEG signals using base-2-meta stacking classifier.

Epilepsy is a chronic neurological disease, characterized by spontaneous, unprovoked, recurrent seizures that may lead to long-term disability and premature death. Despite significant efforts made to improve epilepsy detection clinically and pre-clinically, the pervasive presence of noise in EEG signals continues to pose substantial challenges to their effective application. In addition, discriminant features for epilepsy detection have not been investigated yet. The objective of this study is to develop a hybrid model for epilepsy detection from noisy and fragmented EEG signals. We hypothesized that a hybrid model could surpass existing single models in epilepsy detection. Our approach involves manual noise rejection and a novel statistical channel selection technique to detect epilepsy even from noisy EEG signals. Our proposed Base-2-Meta stacking classifier achieved notable accuracy (0.98 ± 0.05), precision (0.98 ± 0.07), recall (0.98 ± 0.05), and F1 score (0.98 ± 0.04) even with noisy 5-s segmented EEG signals. Application of our approach to the specific problem like detection of epilepsy from noisy and fragmented EEG data reveals a performance that is not only superior to others, but also is translationally relevant, highlighting its potential application in a clinic setting, where EEG signals are often noisy or scanty. Our proposed metric DF-A (Discriminant feature-accuracy), for the first time, identified the most discriminant feature with models that give A accuracy or above (A = 95 used in this study). This groundbreaking approach allows for detecting discriminant features and can be used as potential electrographic biomarkers in epilepsy detection research. Moreover, our study introduces innovative insights into the understanding of these features, epilepsy detection, and cross-validation, markedly improving epilepsy detection in ways previously unavailable.

Investigating population-specific epilepsy detection from noisy EEG signals using deep-learning models.

"Epilepsy is a chronic brain disorder that affects people of all ages. The cause of epilepsy is often unknown and its effect in different age groups is not yet investigated. The main objective of this study is to introduce a novel approach that successfully detects epilepsy even from noisy EEG signals. In addition, this study also investigates population specific epilepsy detection for providing novel insights. Correspondingly, we utilized the TUH EEG corpus database, publicly available challenging multi-channel EEG database containing detailed patient information. We applied a band-pass filter and manual noise rejection to remove noise and artifacts from EEG signals. We then utilized statistical features and correlation to select channels, and applied different transform analysis methods such as continuous wavelet transform, spectrogram, and Wigner-Ville distribution, with and without ensemble averaging, to construct an image dataset. Afterwards, we used various deep-learning models for general analysis. Our findings suggest that different models such as DenseNet201, DenseNet169, DenseNet121, VGG16, VGG19, Xception, InceptionV3, and MobileNetV2 performed better while using images generated from different approaches in general analysis. Furthermore, we split the dataset into two sections according to age for population analysis. All the models that performed well in the general analysis were used for population analysis, which provided novel insights in epilepsy detection from EEG. Our proposed framework for epilepsy detection achieved 100% accuracy, which outperforms other concurrent methods."

Socio-demographic and injury-related factors contributing to activity limitations and participation restrictions in people with spinal cord injury in Bangladesh.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To identify socio-demographic and injury-related factors that contribute to activity limitations and participation restrictions in people with spinal cord injury (SCI) in Bangladesh. SETTING: Centre for the Rehabilitation of the Paralysed (CRP), Savar, Dhaka, Bangladesh. METHODS: This study involved 120 (83% men) participants with SCI; their median (interquartile range) age and injury duration were 34 (25-43) years and 5 (2-10) years, respectively. Data were collected from the follow-up records kept by the Community Based Rehabilitation (CBR) unit of CRP and a subsequent home visit that included interview-administered questions, questionnaires, and a neurological examination. The dependent variables were activity limitations and participation restrictions, assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0, scored 0-100; a high score indicates greater activity limitations and participation restrictions). Independent variables included socio-demographic factors (i.e., age, sex, marital status, educational level, monthly household income, employment status, and place of residence) and injury-related factors (i.e., injury duration, cause of injury, injury severity, and type of paralysis). Multivariable linear regression analyses were performed to identify the factors that independently contributed to activity limitations and participation restrictions. RESULTS: Three significant independent variables explained 20.7% of the variance in activity limitations and participation restrictions (WHODAS 2.0 score), in which tetraplegia was the strongest significant contributing factor, followed by rural residence and complete injury. CONCLUSIONS: This study would indicate that tetraplegia, complete injury, and residing in a rural area are the major contributions in limiting the activity and participation following SCI in Bangladesh.