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1.
PLoS One ; 19(6): e0303597, 2024.
Article in English | MEDLINE | ID: mdl-38905197

ABSTRACT

The battle against viral drug resistance highlights the need for innovative approaches to replace time-consuming and costly traditional methods. Deep generative models offer automation potential, especially in the fight against Human immunodeficiency virus (HIV), as they can synthesize diverse molecules effectively. In this paper, an application of an LSTM-based deep generative model named "LSTM-ProGen" is proposed to be tailored explicitly for the de novo design of drug candidate molecules that interact with a specific target protein (HIV-1 protease). LSTM-ProGen distinguishes itself by employing a long-short-term memory (LSTM) architecture, to generate novel molecules target specificity against the HIV-1 protease. Following a thorough training process involves fine-tuning LSTM-ProGen on a diverse range of compounds sourced from the ChEMBL database. The model was optimized to meet specific requirements, with multiple iterations to enhance its predictive capabilities and ensure it generates molecules that exhibit favorable target interactions. The training process encompasses an array of performance evaluation metrics, such as drug-likeness properties. Our evaluation includes extensive silico analysis using molecular docking and PCA-based visualization to explore the chemical space that the new molecules cover compared to those in the training set. These evaluations reveal that a subset of 12 de novo molecules generated by LSTM-ProGen exhibit a striking ability to interact with the target protein, rivaling or even surpassing the efficacy of native ligands. Extended versions with further refinement of LSTM-ProGen hold promise as versatile tools for designing efficacious and customized drug candidates tailored to specific targets, thus accelerating drug development and facilitating the discovery of new therapies for various diseases.


Subject(s)
Acquired Immunodeficiency Syndrome , Drug Design , HIV Protease Inhibitors , HIV Protease , HIV-1 , HIV Protease Inhibitors/therapeutic use , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/chemistry , Humans , HIV Protease/metabolism , HIV Protease/chemistry , HIV-1/drug effects , Acquired Immunodeficiency Syndrome/drug therapy , Molecular Docking Simulation
2.
Cancers (Basel) ; 16(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38611113

ABSTRACT

SET-domain containing 2 (SETD2) is a histone methyltransferase and an epigenetic modifier with oncogenic functionality. In the current study, we investigated the potential prognostic role of SETD2 in prostate cancer. A cohort of 202 patients' samples was assembled on tissue microarrays (TMAs) containing incidental, advanced, and castrate-resistant CRPCa cases. Our data showed significant elevated SETD2 expression in advanced and castrate-resistant disease (CRPCa) compared to incidental cases (2.53 ± 0.58 and 2.21 ± 0.63 vs. 1.9 ± 0.68; p < 0.001, respectively). Interestingly, the mean intensity of SETD2 expression in deceased vs. alive patients was also significantly different (2.31 ± 0.66 vs. 2 ± 0.68; p = 0.003, respectively). Overall, high SETD2 expression was found to be considered high risk and was significantly associated with poor prognosis and worse overall survival (OS) (HR 1.80; 95% CI: 1.28-2.53, p = 0.001) and lower cause specific survival (CSS) (HR 3.14; 95% CI: 1.94-5.08, p < 0.0001). Moreover, combining high-intensity SETD2 with PTEN loss resulted in lower OS (HR 2.12; 95% CI: 1.22-3.69, p = 0.008) and unfavorable CSS (HR 3.74; 95% CI: 1.67-8.34, p = 0.001). Additionally, high SETD2 intensity with ERG positive expression showed worse prognosis for both OS (HR 1.99, 95% CI 0.87-4.59; p = 0.015) and CSS (HR 2.14, 95% CI 0.98-4.68, p = 0.058). We also investigated the protein expression database TCPA, and our results showed that high SETD2 expression is associated with a poor prognosis. Finally, we performed TCGA PRAD gene set enrichment analysis (GSEA) data for SETD2 overexpression, and our data revealed a potential association with pathways involved in tumor progression such as the AMPK signaling pathway, the cAMP signaling pathway, and the PI3K-Akt signaling pathway, which are potentially associated with tumor progression, chemoresistance, and a poor prognosis.

3.
Med Biol Eng Comput ; 62(1): 1-45, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37700082

ABSTRACT

Medical imaging, also known as radiology, is the field of medicine in which medical professionals recreate various images of parts of the body for diagnostic or treatment purposes. Medical imaging procedures include non-invasive tests that allow doctors to diagnose injuries and diseases without being intrusive TechTarget (n.d.). A number of tools and techniques are used to automate the analysis of medical images acquired with various image processing methods. The brain is one of the largest and most complex organs of the human body and anomaly detection from brain images (i.e., MRI, CT, PET, etc.) is one of the major research areas of medical image analysis. Image processing methods such as filtering and thresholding models, geometry models, graph models, region-based analysis, connected component analysis, machine learning (ML) models, the recent deep learning (DL) models, and various hybrid models are used in brain image analysis. Brain tumors are one of the most common brain diseases with a high mortality rate, and it is difficult to analyze from brain images for the versatility of the shape, location, size, texture, and other characteristics. In this paper, a comprehensive review on brain tumor image analysis is presented with basic ideas of brain tumor, brain imaging, brain image analysis tasks, brain image analysis models, brain tumor image features, performance metrics used for evaluating the models, and some available datasets on brain tumor/medical images. Some challenges of brain tumor analysis are also discussed including suggestions for future research directions. The graphical abstract summarizes the contributions of this paper.


Subject(s)
Brain Neoplasms , Image Processing, Computer-Assisted , Humans , Image Processing, Computer-Assisted/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain/diagnostic imaging , Brain/pathology , Magnetic Resonance Imaging , Machine Learning
4.
Cancers (Basel) ; 15(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37835496

ABSTRACT

Cancer in all its forms of expression is a major cause of death. To identify the genomic reason behind cancer, discovery of biomarkers is needed. In this paper, genomic data of bladder cancer are examined for the purpose of biomarker discovery. Genomic biomarkers are indicators stemming from the study of the genome, either at a very low level based on the genome sequence itself, or more abstractly such as measuring the level of gene expression for different disease groups. The latter method is pivotal for this work, since the available datasets consist of RNA sequencing data, transformed to gene expression levels, as well as data on a multitude of clinical indicators. Based on this, various methods are utilized such as statistical modeling via logistic regression and regularization techniques (elastic-net), clustering, survival analysis through Kaplan-Meier curves, and heatmaps for the experiments leading to biomarker discovery. The experiments have led to the discovery of two gene signatures capable of predicting therapy response and disease progression with considerable accuracy for bladder cancer patients which correlates well with clinical indicators such as Therapy Response and T-Stage at surgery with Disease Progression in a time-to-event manner.

5.
Cancers (Basel) ; 15(10)2023 May 22.
Article in English | MEDLINE | ID: mdl-37345203

ABSTRACT

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT's potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.

6.
PLoS One ; 18(4): e0284418, 2023.
Article in English | MEDLINE | ID: mdl-37068084

ABSTRACT

Brain cancers caused by malignant brain tumors are one of the most fatal cancer types with a low survival rate mostly due to the difficulties in early detection. Medical professionals therefore use various invasive and non-invasive methods for detecting and treating brain tumors at the earlier stages thus enabling early treatment. The main non-invasive methods for brain tumor diagnosis and assessment are brain imaging like computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI) scans. In this paper, the focus is on detection and segmentation of brain tumors from 2D and 3D brain MRIs. For this purpose, a complete automated system with a web application user interface is described which detects and segments brain tumors with more than 90% accuracy and Dice scores. The user can upload brain MRIs or can access brain images from hospital databases to check presence or absence of brain tumor, to check the existence of brain tumor from brain MRI features and to extract the tumor region precisely from the brain MRI using deep neural networks like CNN, U-Net and U-Net++. The web application also provides an option for entering feedbacks on the results of the detection and segmentation to allow healthcare professionals to add more precise information on the results that can be used to train the model for better future predictions and segmentations.


Subject(s)
Brain Neoplasms , Trust , Humans , Feedback , Neural Networks, Computer , Radiopharmaceuticals , Brain Neoplasms/diagnostic imaging , Brain , Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods
7.
Sci Rep ; 13(1): 2704, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36792691

ABSTRACT

Splicing factor 3B subunit 1 (SF3B1) is the largest component of SF3b protein complex which is involved in the pre-mRNA splicing mechanism. Somatic mutations of SF3B1 were shown to be associated with aberrant splicing, producing abnormal transcripts that drive cancer development and/or prognosis. In this study, we focus on the relationship between SF3B1 and four types of cancer, namely myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL) and breast cancer (BC). For this purpose, we identified from the Pubmed library only articles which mentioned SF3B1 in connection with the investigated types of cancer for the period 2007 to 2018 to reveal how the connection has developed over time. We left out all published articles which mentioned SF3B1 in other contexts. We retrieved the target articles and investigated the association between SF3B1 and the mentioned four types of cancer. For this we utilized some of the publicly available databases to retrieve gene/variant/disease information related to SF3B1. We used the outcome to derive and analyze a variety of complex networks that reflect the correlation between the considered diseases and variants associated with SF3B1. The results achieved based on the analyzed articles and reported in this article illustrated that SF3B1 is associated with hematologic malignancies, such as MDS, AML, and CLL more than BC. We found that different gene networks may be required for investigating the impact of mutant splicing factors on cancer development based on the target cancer type. Additionally, based on the literature analyzed in this study, we highlighted and summarized what other researchers have reported as the set of genes and cellular pathways that are affected by aberrant splicing in cancerous cells.


Subject(s)
Breast Neoplasms , Leukemia, Lymphocytic, Chronic, B-Cell , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Female , Ribonucleoprotein, U2 Small Nuclear/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , RNA Splicing , Myelodysplastic Syndromes/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Transcription Factors/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism
8.
Med Biol Eng Comput ; 61(6): 1257-1297, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36707488

ABSTRACT

The ongoing COVID-19 pandemic caused by the SARS-CoV-2 virus has already resulted in 6.6 million deaths with more than 637 million people infected after only 30 months since the first occurrences of the disease in December 2019. Hence, rapid and accurate detection and diagnosis of the disease is the first priority all over the world. Researchers have been working on various methods for COVID-19 detection and as the disease infects lungs, lung image analysis has become a popular research area for detecting the presence of the disease. Medical images from chest X-rays (CXR), computed tomography (CT) images, and lung ultrasound images have been used by automated image analysis systems in artificial intelligence (AI)- and machine learning (ML)-based approaches. Various existing and novel ML, deep learning (DL), transfer learning (TL), and hybrid models have been applied for detecting and classifying COVID-19, segmentation of infected regions, assessing the severity, and tracking patient progress from medical images of COVID-19 patients. In this paper, a comprehensive review of some recent approaches on COVID-19-based image analyses is provided surveying the contributions of existing research efforts, the available image datasets, and the performance metrics used in recent works. The challenges and future research scopes to address the progress of the fight against COVID-19 from the AI perspective are also discussed. The main objective of this paper is therefore to provide a summary of the research works done in COVID detection and analysis from medical image datasets using ML, DL, and TL models by analyzing their novelty and efficiency while mentioning other COVID-19-based review/survey researches to deliver a brief overview on the maximum amount of information on COVID-19-based existing researches.


Subject(s)
COVID-19 , Deep Learning , Humans , SARS-CoV-2 , Artificial Intelligence , Pandemics , Machine Learning
9.
PLoS One ; 17(12): e0278236, 2022.
Article in English | MEDLINE | ID: mdl-36548250

ABSTRACT

Entropy is an alternative measure to calculate the risk, simplify the portfolios and equity risk premium. It has higher explanatory power than capital asset price model (CAPM) beta. The comparison of Entropy and CAPM beta provide in depth analysis about the explanatory power of the model that in turn help investor to make right investment decisions that minimizes risk. In this context, this study aims to compare Shannon and Rennyi Entropies with the CAPM beta for measuring the risk. Ordinary Least square approach has been utilized using a dataset of 67 enterprises registered in Pakistan Stock exchange. The comparative analysis of CAPM beta and entropy has been carried out with the R2 parameters. The result indicates that entropy has more explanatory power as compare to CAPM beta's explanatory power, and this turns out to be the best option to evaluate the risk performances. The result implies that an investor should make the best investment decision by choosing an enterprise that provide with good returns at minimum risk based on entropy technique.


Subject(s)
Financial Statements , Entropy , Pakistan , Costs and Cost Analysis , Risk
10.
PLoS One ; 17(12): e0278487, 2022.
Article in English | MEDLINE | ID: mdl-36548288

ABSTRACT

Due to the severity and speed of spread of the ongoing Covid-19 pandemic, fast but accurate diagnosis of Covid-19 patients has become a crucial task. Achievements in this respect might enlighten future efforts for the containment of other possible pandemics. Researchers from various fields have been trying to provide novel ideas for models or systems to identify Covid-19 patients from different medical and non-medical data. AI-based researchers have also been trying to contribute to this area by mostly providing novel approaches of automated systems using convolutional neural network (CNN) and deep neural network (DNN) for Covid-19 detection and diagnosis. Due to the efficiency of deep learning (DL) and transfer learning (TL) models in classification and segmentation tasks, most of the recent AI-based researches proposed various DL and TL models for Covid-19 detection and infected region segmentation from chest medical images like X-rays or CT images. This paper describes a web-based application framework for Covid-19 lung infection detection and segmentation. The proposed framework is characterized by a feedback mechanism for self learning and tuning. It uses variations of three popular DL models, namely Mask R-CNN, U-Net, and U-Net++. The models were trained, evaluated and tested using CT images of Covid patients which were collected from two different sources. The web application provide a simple user friendly interface to process the CT images from various resources using the chosen models, thresholds and other parameters to generate the decisions on detection and segmentation. The models achieve high performance scores for Dice similarity, Jaccard similarity, accuracy, loss, and precision values. The U-Net model outperformed the other models with more than 98% accuracy.


Subject(s)
COVID-19 , Trust , Humans , Feedback , COVID-19/diagnostic imaging , Pandemics , Neural Networks, Computer
11.
Nutr Health ; : 2601060221129142, 2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36198038

ABSTRACT

Purpose: Recent studies in economics showed that humans are bounded rational. This being consumers, they are not perfect judges of what matters for the standard of living. While with a marked increase in economic and social wellbeing, there is a consistent rise in obesity levels, especially in the developed world. Thus, this study intends to explore the empirical and socio-economic antecedents of human obesity across countries using six global indexes. Methods: This study used the data of 40 countries between 1975 to 2018 and used the Panel FGLS Regression with the quadratic specification. Findings: The results showed that health and food indicators increase global human obesity, environment and education indicators decrease global human obesity, and economic and social indicators follow an inverted U-shaped pattern in affecting global human obesity. Originality: Previous studies have used infant mortality and life expectancy as the major health indicator in determining the standard of living while overlooking global human obesity as a major deterrent to welfare. This study has provided a holistic assessment of the causes of obesity in global contexts.

12.
Nutr Health ; : 2601060221125146, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36113142

ABSTRACT

Purpose - Political globalization is a crucial and distinct component of strengthening global organizations. Obesity is a global epidemic in a few nations, and it is on the verge of becoming a pandemic that would bring plenty of diseases. This research aims to see how the political globalization index affects worldwide human obesity concerning global human development levels. Methods- To assess any cross-sectional dependence among observed 109 nations, the yearly period from 1990 to 2017 is analyzed using second generation panel data methods. KAO panel cointegration test and Fully Modified Least Square model were used to meet our objectives. Finding- Low level of political globalization tends to increase global human obesity because countries cannot sway international decisions and resources towards them. While the high level of political globalization tends to reduce obesity because it can control and amends international decisions. For the regression model, a fully modified Least Square model was utilized. The study observed that the R squared values for all models are healthy, with a minimum of 87 percent variables explaining differences in global obesity at the country level. Originality: There is very important to tackle the globalization issue to reduce global human obesity. With the simplicity of dietary options and the amount of physical labour they undergo in their agricultural duties, an increase in rural population percentage tends to lower the average national obesity value.

13.
Sci Rep ; 12(1): 15210, 2022 09 08.
Article in English | MEDLINE | ID: mdl-36075941

ABSTRACT

We propose a new type of supervised visual machine learning classifier, GSNAc, based on graph theory and social network analysis techniques. In a previous study, we employed social network analysis techniques and introduced a novel classification model (called Social Network Analysis-based Classifier-SNAc) which efficiently works with time-series numerical datasets. In this study, we have extended SNAc to work with any type of tabular data by showing its classification efficiency on a broader collection of datasets that may contain numerical and categorical features. This version of GSNAc simply works by transforming traditional tabular data into a network where samples of the tabular dataset are represented as nodes and similarities between the samples are reflected as edges connecting the corresponding nodes. The raw network graph is further simplified and enriched by its edge space to extract a visualizable 'graph classifier model-GCM'. The concept of the GSNAc classification model relies on the study of node similarities over network graphs. In the prediction step, the GSNAc model maps test nodes into GCM, and evaluates their average similarity to classes by employing vectorial and topological metrics. The novel side of this research lies in transforming multidimensional data into a 2D visualizable domain. This is realized by converting a conventional dataset into a network of 'samples' and predicting classes after a careful and detailed network analysis. We exhibit the classification performance of GSNAc as an effective classifier by comparing it with several well-established machine learning classifiers using some popular benchmark datasets. GSNAc has demonstrated superior or comparable performance compared to other classifiers. Additionally, it introduces a visually comprehensible process for the benefit of end-users. As a result, the spin-off contribution of GSNAc lies in the interpretability of the prediction task since the process is human-comprehensible; and it is highly visual.


Subject(s)
Artificial Intelligence , Social Network Analysis , Humans , Machine Learning
14.
Bioengineering (Basel) ; 10(1)2022 Dec 24.
Article in English | MEDLINE | ID: mdl-36671598

ABSTRACT

The eye is generally considered to be the most important sensory organ of humans. Diseases and other degenerative conditions of the eye are therefore of great concern as they affect the function of this vital organ. With proper early diagnosis by experts and with optimal use of medicines and surgical techniques, these diseases or conditions can in many cases be either cured or greatly mitigated. Experts that perform the diagnosis are in high demand and their services are expensive, hence the appropriate identification of the cause of vision problems is either postponed or not done at all such that corrective measures are either not done or done too late. An efficient model to predict eye diseases using machine learning (ML) and ranker-based feature selection (r-FS) methods is therefore proposed which will aid in obtaining a correct diagnosis. The aim of this model is to automatically predict one or more of five common eye diseases namely, Cataracts (CT), Acute Angle-Closure Glaucoma (AACG), Primary Congenital Glaucoma (PCG), Exophthalmos or Bulging Eyes (BE) and Ocular Hypertension (OH). We have used efficient data collection methods, data annotations by professional ophthalmologists, applied five different feature selection methods, two types of data splitting techniques (train-test and stratified k-fold cross validation), and applied nine ML methods for the overall prediction approach. While applying ML methods, we have chosen suitable classic ML methods, such as Decision Tree (DT), Random Forest (RF), Naive Bayes (NB), AdaBoost (AB), Logistic Regression (LR), k-Nearest Neighbour (k-NN), Bagging (Bg), Boosting (BS) and Support Vector Machine (SVM). We have performed a symptomatic analysis of the prominent symptoms of each of the five eye diseases. The results of the analysis and comparison between methods are shown separately. While comparing the methods, we have adopted traditional performance indices, such as accuracy, precision, sensitivity, F1-Score, etc. Finally, SVM outperformed other models obtaining the highest accuracy of 99.11% for 10-fold cross-validation and LR obtained 98.58% for the split ratio of 80:20.

15.
Article in English | MEDLINE | ID: mdl-36612615

ABSTRACT

The continuously increasing GHG emissions have created environmental pollution and several challenges to ecosystems and biodiversity. The challenges of climate change are multipronged, resulting in melting glaciers, flash floods, and severe heat waves. In this regard, the adaptive and mitigation strategies to manage the consequences of climate change are highly important. The transport sector creates a quarter of carbon emissions, and this share is continuously increasing. Accordingly, this research study uses transport competitiveness to determine carbon emissions of the transport sector for 121 countries covering the time period from 2008 to 2018. The Panel Quantile Regression (PQR) technique is engaged to analyze the study results. The findings highlight that transport competitiveness tends to increase carbon emissions of the transport sector across quantile groups 1 and 3, while it reduces carbon emissions in quantile group 2. The U-shaped services' EKC is validated in quantile groups 2 and 4. The moderation engaged, i.e., transportation competitiveness, changes the turning point of the services' EKC across quantile groups 2 and 4. However, in the high-CO2 quantile group, the moderation impact of transport competitiveness is strongest as it reduces the sensitivity by flattening the services' EKC. Furthermore, the planned expansion of the population and improved institutional quality tend to mitigate carbon emissions across different quantile groups. The policy relevance/implications that are based on the study results/findings are made part of the research paper.


Subject(s)
Carbon Dioxide , Ecosystem , Prospective Studies , Climate Change , Carbon , Economic Development
16.
BMC Public Health ; 21(1): 1607, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34470630

ABSTRACT

BACKGROUND: The first half of 2020 has been marked as the era of COVID-19 pandemic which affected the world globally in almost every aspect of the daily life from societal to economical. To prevent the spread of COVID-19, countries have implemented diverse policies regarding Non-Pharmaceutical Intervention (NPI) measures. This is because in the first stage countries had limited knowledge about the virus and its contagiousness. Also, there was no effective medication or vaccines. This paper studies the effectiveness of the implemented policies and measures against the deaths attributed to the virus between January and May 2020. METHODS: Data from the European Centre for Disease Prevention and Control regarding the identified cases and deaths of COVID-19 from 48 countries have been used. Additionally, data concerning the NPI measures related policies implemented by the 48 countries and the capacity of their health care systems was collected manually from their national gazettes and official institutes. Data mining, time series analysis, pattern detection, machine learning, clustering methods and visual analytics techniques have been applied to analyze the collected data and discover possible relationships between the implemented NPIs and COVID-19 spread and mortality. Further, we recorded and analyzed the responses of the countries against COVID-19 pandemic, mainly in urban areas which are over-populated and accordingly COVID-19 has the potential to spread easier among humans. RESULTS: The data mining and clustering analysis of the collected data showed that the implementation of the NPI measures before the first death case seems to be very effective in controlling the spread of the disease. In other words, delaying the implementation of the NPI measures to after the first death case has practically little effect on limiting the spread of the disease. The success of implementing the NPI measures further depends on the way each government monitored their application. Countries with stricter policing of the measures seems to be more effective in controlling the transmission of the disease. CONCLUSIONS: The conducted comparative data mining study provides insights regarding the correlation between the early implementation of the NPI measures and controlling COVID-19 contagiousness and mortality. We reported a number of useful observations that could be very helpful to the decision makers or epidemiologists regarding the rapid implementation and monitoring of the NPI measures in case of a future wave of COVID-19 or to deal with other unknown infectious pandemics. Regardless, after the first wave of COVID-19, most countries have decided to lift the restrictions and return to normal. This has resulted in a severe second wave in some countries, a situation which requires re-evaluating the whole process and inspiring lessons for the future.


Subject(s)
COVID-19 , Pandemics , Data Mining , Government , Humans , Pandemics/prevention & control , SARS-CoV-2
17.
PLoS One ; 16(5): e0251703, 2021.
Article in English | MEDLINE | ID: mdl-34032798

ABSTRACT

Glaucoma is a leading cause of blindness worldwide whose detection is based on multiple factors, including measuring the cup to disc ratio, retinal nerve fiber layer and visual field defects. Advances in image processing and machine learning have allowed the development of automated approached for segmenting objects from fundus images. However, to build a robust system, a reliable ground truth dataset is required for proper training and validation of the model. In this study, we investigate the level of agreement in properly detecting the retinal disc in fundus images using an online portal built for such purposes. Two Doctors of Optometry independently traced the discs for 159 fundus images obtained from publicly available datasets using a purpose-built online portal. Additionally, we studied the effectiveness of ellipse fitting in handling misalignments in tracing. We measured tracing precision, interobserver variability, and average boundary distance between the results provided by ophthalmologists, and optometrist tracing. We also studied whether ellipse fitting has a positive or negative impact on properly detecting disc boundaries. The overall agreement between the optometrists in terms of locating the disc region in these images was 0.87. However, we found that there was a fair agreement on the disc border with kappa = 0.21. Disagreements were mainly in fundus images obtained from glaucomatous patients. The resulting dataset was deemed to be an acceptable ground truth dataset for training a validation of models for automatic detection of objects in fundus images.


Subject(s)
Datasets as Topic , Glaucoma/diagnosis , Image Interpretation, Computer-Assisted/methods , Internet , Optic Disk/diagnostic imaging , Blindness/etiology , Blindness/prevention & control , Crowdsourcing , Fundus Oculi , Glaucoma/complications , Humans , Machine Learning , Observer Variation , Optometrists/statistics & numerical data , Validation Studies as Topic
18.
J Cancer Res Clin Oncol ; 147(8): 2223-2231, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33864110

ABSTRACT

INTRODUCTION AND OBJECTIVES: ISL1 serves as a biomarker of metastasis and neuroendocrine neoplasia in multiple tumors. However, the expression and relation of ISL1 to other biomarkers in prostate cancer have not been fully elucidated. Here, we characterize the expression of ISL1 and its partners in PCa and document its association to disease progression and post castration resistance neuroendocrine differentiation. METHODS: The expression of ISL1 was interrogated in > 6000 primary samples from the Decipher GRID registry and 250 mCRPC samples to assess its prognostic value and relation to neuroendocrine differentiation. RESULTS: ISL1 was highly correlated to MEIS genes and other genes related to cell motility. ISL1 down-regulation in PCa was associated with cancer progression, aggressive primary tumors, and metastatic outcome. We found that ISL1 is highly correlated to MEIS genes across multiple primary PCa and mCRPC cohorts. The expression of ISL1 and MEIS genes were significantly and inversely related to metastasis-free survival and lethal disease, and were downregulated in CRPC and hormone naïve metastatic tumors but showed upregulation in neuroendocrine tumors. Co-immunoprecipitation showed MEIS2 and ISL1 interacting with each supporting their role in modulating transcriptional regulation and nominating this complex for potential targeted therapy. CONCLUSIONS: ISL1 complex with MEIS2 serves a critical role in prostate tumor progression and its upregulation in mCRPC/NE provides a rationale for assessing the role of ISL1 and its associated protein in treatment resistance.


Subject(s)
Homeodomain Proteins/genetics , LIM-Homeodomain Proteins/genetics , Neuroendocrine Tumors/genetics , Prostatic Neoplasms/genetics , Transcription Factors/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Differentiation/genetics , Cell Line, Tumor , Disease Progression , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/metabolism , Humans , LIM-Homeodomain Proteins/metabolism , Male , Myeloid Ecotropic Viral Integration Site 1 Protein/genetics , Myeloid Ecotropic Viral Integration Site 1 Protein/metabolism , Neuroendocrine Tumors/pathology , Prostatic Neoplasms/pathology , Protein Binding , Transcription Factors/metabolism
19.
BMC Bioinformatics ; 22(1): 28, 2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33482713

ABSTRACT

BACKGROUND: Drug repositioning is an emerging approach in pharmaceutical research for identifying novel therapeutic potentials for approved drugs and discover therapies for untreated diseases. Due to its time and cost efficiency, drug repositioning plays an instrumental role in optimizing the drug development process compared to the traditional de novo drug discovery process. Advances in the genomics, together with the enormous growth of large-scale publicly available data and the availability of high-performance computing capabilities, have further motivated the development of computational drug repositioning approaches. More recently, the rise of machine learning techniques, together with the availability of powerful computers, has made the area of computational drug repositioning an area of intense activities. RESULTS: In this study, a novel framework SNF-NN based on deep learning is presented, where novel drug-disease interactions are predicted using drug-related similarity information, disease-related similarity information, and known drug-disease interactions. Heterogeneous similarity information related to drugs and disease is fed to the proposed framework in order to predict novel drug-disease interactions. SNF-NN uses similarity selection, similarity network fusion, and a highly tuned novel neural network model to predict new drug-disease interactions. The robustness of SNF-NN is evaluated by comparing its performance with nine baseline machine learning methods. The proposed framework outperforms all baseline methods ([Formula: see text] = 0.867, and [Formula: see text]=0.876) using stratified 10-fold cross-validation. To further demonstrate the reliability and robustness of SNF-NN, two datasets are used to fairly validate the proposed framework's performance against seven recent state-of-the-art methods for drug-disease interaction prediction. SNF-NN achieves remarkable performance in stratified 10-fold cross-validation with [Formula: see text] ranging from 0.879 to 0.931 and [Formula: see text] from 0.856 to 0.903. Moreover, the efficiency of SNF-NN is verified by validating predicted unknown drug-disease interactions against clinical trials and published studies. CONCLUSION: In conclusion, computational drug repositioning research can significantly benefit from integrating similarity measures in heterogeneous networks and deep learning models for predicting novel drug-disease interactions. The data and implementation of SNF-NN are available at http://pages.cpsc.ucalgary.ca/ tnjarada/snf-nn.php .


Subject(s)
Computational Biology , Drug Repositioning , Pharmaceutical Preparations , Algorithms , Drug Therapy , Neural Networks, Computer , Reproducibility of Results
20.
IEEE Access ; 9: 30551-30572, 2021.
Article in English | MEDLINE | ID: mdl-34976571

ABSTRACT

Novel coronavirus (COVID-19) outbreak, has raised a calamitous situation all over the world and has become one of the most acute and severe ailments in the past hundred years. The prevalence rate of COVID-19 is rapidly rising every day throughout the globe. Although no vaccines for this pandemic have been discovered yet, deep learning techniques proved themselves to be a powerful tool in the arsenal used by clinicians for the automatic diagnosis of COVID-19. This paper aims to overview the recently developed systems based on deep learning techniques using different medical imaging modalities like Computer Tomography (CT) and X-ray. This review specifically discusses the systems developed for COVID-19 diagnosis using deep learning techniques and provides insights on well-known data sets used to train these networks. It also highlights the data partitioning techniques and various performance measures developed by researchers in this field. A taxonomy is drawn to categorize the recent works for proper insight. Finally, we conclude by addressing the challenges associated with the use of deep learning methods for COVID-19 detection and probable future trends in this research area. The aim of this paper is to facilitate experts (medical or otherwise) and technicians in understanding the ways deep learning techniques are used in this regard and how they can be potentially further utilized to combat the outbreak of COVID-19.

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