Predictive accuracy of boosted regression model in estimating risk of venous thromboembolism following minimally invasive radical surgery in pharmacological prophylaxis-naïve men with prostate cancer

Background: Venous thromboembolism (VTE) is a potentially life-threatening but preventable complication after urological surgery. Physicians are faced with the challenges of weighing the risks and benefits of thromboprophylaxis given scanty evidence for or against and practice variation worldwide.Objective: The primary objective of the study was to explore the possibility of a risk-stratified approach for thromboembolism prophylaxis following radical prostatectomy.Design, setting, and participants: A prospective database was accessed to cross-link venous thromboembolism events in 522 men who underwent minimally invasive prostatectomy between February 2010 and October 2021. A deterministic data linkage method was used to record events through electronic systems. Community Health Index (CHI) numbers were used to identify patients via electronic health records. Patient demographics and clinical characteristics such as age, comorbidities, Gleason staging, and readmission details accrued.Outcomes: VTE within 90 days and development of a risk-stratified scoring system. All statistical analysis was performed using R-Statistical Software and the risk of VTE within 90 days of surgery was estimated via gradient-boosting decision trees (BRT) model.Results and limitations: 1.1% (6/522) of patients developed deep vein thrombosis or pulmonary embolism within 3 months post-minimally invasive prostatectomy. Statistical analysis demonstrated a significant difference in the body mass index (p = 0.016), duration of hospital stay (p &lt; 0.001), and number of readmissions (p = 0.036) between patients who developed VTE versus patients who did not develop VTE. BRT analysis found 8 variables that demonstrated relative importance in predicting VTE. The receiver operating curves (ROC) were constructed to assess the discrimination power of a new model. The model showed an AUC of 0.97 (95% confidence intervals [CI]: 0.945,0.999). For predicting VTE, a single-center study is a limitation.Conclusions: The incidence of VTE post-minimally invasive prostatectomy in men who did not receive prophylaxis with low molecular weight heparin is low (1.1%). The proposed risk-scoring system may aid in the identification of higher-risk patients for thromboprophylaxis. Patient summary: In this report, we looked at the outcomes of venous thromboembolism following minimally invasive radical prostatectomy for prostate cancer in consecutive men. We developed a new scoring system using advanced statistical analysis. We conclude that the VTE risk is very low and our model, if applied, can risk stratify men for the development of VTE following radical surgery for prostate cancer.</p

Prediction of clinically significant cancer using radiomics features of pre-biopsy of multiparametric MRi in men suspected of prostate cancer

SIMPLE SUMMARY: Radiomics is the field of computer-based medical image analysis that incorporates various radiological imaging features, such as texture and shape parameters, from scans to derive algorithms. These mathematical algorithms have the potential to predict the biological characteristics of disease. In this study, we obtained quantitative imaging texture features of pre-biopsy multiparametric MRI of men suspected of prostate cancer and extracted from the T2WI and ADC images focusing on gray-level co-occurrence matrices (GLCM). These were correlated with the Gleason score of the histopathology of radical prostatectomy specimen, including the prediction of clinically significant prostate cancer. The knowledge gained through this prospective protocol-based study should facilitate establishing that GLCM texture features alone can be used as a biomarker for predicting the presence of clinically significant PCa. ABSTRACT: Background: Texture features based on the spatial relationship of pixels, known as the gray-level co-occurrence matrix (GLCM), may play an important role in providing the accurate classification of suspected prostate cancer. The purpose of this study was to use quantitative imaging parameters of pre-biopsy multiparametric magnetic resonance imaging (mpMRI) for the prediction of clinically significant prostate cancer. Methods: This was a prospective study, recruiting 200 men suspected of having prostate cancer. Participants were imaged using a protocol-based 3T MRI in the pre-biopsy setting. Radiomics parameters were extracted from the T2WI and ADC texture features of the gray-level co-occurrence matrix were delineated from the region of interest. Radical prostatectomy histopathology was used as a reference standard. A Kruskal–Wallis test was applied first to identify the significant radiomic features between the three groups of Gleason scores (i.e., G1, G2 and G3). Subsequently, the Holm–Bonferroni method was applied to correct and control the probability of false rejections. We compared the probability of correctly predicting significant prostate cancer between the explanatory GLCM radiomic features, PIRADS and PSAD, using the area under the receiver operation characteristic curves. Results: We identified the significant difference in radiomic features between the three groups of Gleason scores. In total, 12 features out of 22 radiomics features correlated with the Gleason groups. Our model demonstrated excellent discriminative ability (C-statistic = 0.901, 95%CI 0.859–0.943). When comparing the probability of correctly predicting significant prostate cancer between explanatory GLCM radiomic features (Sum Variance T2WI, Sum Entropy T2WI, Difference Variance T2WI, Entropy ADC and Difference Variance ADC), PSAD and PIRADS via area under the ROC curve, radiomic features were 35.0% and 34.4% more successful than PIRADS and PSAD, respectively, in correctly predicting significant prostate cancer in our patients (p < 0.001). The Sum Entropy T2WI score had the greatest impact followed by the Sum Variance T2WI. Conclusion: Quantitative GLCM texture analyses of pre-biopsy MRI has the potential to be used as a non-invasive imaging technique to predict clinically significant cancer in men suspected of having prostate cancer

Radiogenomics map-based molecular and imaging phenotypical characterization in localised prostate cancer using pre-biopsy biparametric MR imaging

Objective: To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard.Methods: Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n=15) across different Gleason scorebased risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model.Results: A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value= ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95.Conclusion: Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into prediction model improved prediction accuracy of clinically significant prostate cancer

Radiogenomics map-based molecular and imaging phenotypical characterization in localised prostate cancer using pre-biopsy biparametric MR imaging

Objective: To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard.Methods: Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n=15) across different Gleason scorebased risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model.Results: A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value= ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95.Conclusion: Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into prediction model improved prediction accuracy of clinically significant prostate cancer

A Sustainable Green Supply Chain Model with Carbon Emissions for Defective Items under Learning in a Fuzzy Environment

Assuming the significance of sustainability, it is considered necessary to ensure the conservation of our natural resources, in addition to minimizing waste. To promote significant sustainable effects, factors including production, transportation, energy usage, product control management, etc., act as the chief supports of any modern supply chain model. The buyer performs the firsthand inspection and returns any defective items received from the customer to the vendor in a process that is known as first-level inspection. The vendor uses the policy of recovery product management to obtain greater profit. A concluding inspection is accomplished at the vendor’s end in order to distinguish the returned item as belonging to one of four specific categories, namely re-workable, reusable, recyclable, and disposable, a process that is known as second-level inspection. Then, it is observed that some defective items are suitable for a secondary market, while some are reusable, and some can be disassembled to shape new derived products, and leftovers can be scrapped at the disposal cost. This ensures that we can meet our target to promote a cleaner drive with a lower percentage of carbon emissions, reducing the adverse effects of landfills. The activity of both players in this model is presented briefly in the flowchart shown in the abstract. Thus, our aim of product restoration is to promote best practices while maintaining economic value, with the ultimate goal of removing the surrounding waste with minimum financial costs. In this regard, it is assumed that the demand rate is precise in nature. The learning effect and fuzzy environment are also considered in the present model. The proposed model studies the impacts of learning and carbon emissions on an integrated green supply chain model for defective items in fuzzy environment and shortage conditions. We optimized the integrated total fuzzy profit with respect to the order quantity and shortages. We described the vendor’s strategy and buyer’s strategy through flowcharts for the proposed integrated supply chain model, and here, in the flowchart, R-R-R stands for re-workable, reusable, and recyclable. The demand rate was treated as a triangular fuzzy number. In this paper, a numerical example, sensitivity analysis, limitations, future scope, and conclusion are presented for the validation of the proposed model

Multivariate limit of detection for non-linear sensor arrays

With the increased development of low-cost and miniature devices, sensors are increasingly being deployed as arrays of redundant sensors. However, little work has been done characterizing properties of these arrays. Here, we develop and test a Bayesian algorithm for estimating the limit of detection of sensor arrays. The algorithm is applicable for single sensors as well as sensor arrays, and works by reducing a vector in the signal domain to a univariate response in the measurand domain. We show that the new algorithm can reproduce results from a benchmark algorithm for single sensors, and then demonstrate the benefit of adding additional sensors to an array. Then, we provide guidelines that achieve numerical stability while minimising computational cost. Finally, we provide a real-world example using an array of ion-selective electrodes measuring carbonate in seawater. This application demonstrates how incorporation of a set of individual low-quality sensors into an array leads to a substantially reduced LOD that clearly meets the demands of the application

Radiogenomics Reveals Correlation between Quantitative Texture Radiomic Features of Biparametric MRI and Hypoxia-Related Gene Expression in Men with Localised Prostate Cancer

Objectives: To perform multiscale correlation analysis between quantitative texture feature phenotypes of pre-biopsy biparametric MRI (bpMRI) and targeted sequence-based RNA expression for hypoxia-related genes. Materials and Methods: Images from pre-biopsy 3T bpMRI scans in clinically localised PCa patients of various risk categories (n = 15) were used to extract textural features. The genomic landscape of hypoxia-related gene expression was obtained using post-radical prostatectomy tissue for targeted RNA expression profiling using the TempO-sequence method. The nonparametric Games Howell test was used to correlate the differential expression of the important hypoxia-related genes with 28 radiomic texture features. Then, cBioportal was accessed, and a gene-specific query was executed to extract the Oncoprint genomic output graph of the selected hypoxia-related genes from The Cancer Genome Atlas (TCGA). Based on each selected gene profile, correlation analysis using Pearson’s coefficients and survival analysis using Kaplan–Meier estimators were performed. Results: The quantitative bpMR imaging textural features, including the histogram and grey level co-occurrence matrix (GLCM), correlated with three hypoxia-related genes (ANGPTL4, VEGFA, and P4HA1) based on RNA sequencing using the TempO-Seq method. Further radiogenomic analysis, including data accessed from the cBioportal genomic database, confirmed that overexpressed hypoxia-related genes significantly correlated with a poor survival outcomes, with a median survival ratio of 81.11:133.00 months in those with and without alterations in genes, respectively. Conclusion: This study found that there is a correlation between the radiomic texture features extracted from bpMRI in localised prostate cancer and the hypoxia-related genes that are differentially expressed. The analysis of expression data based on cBioportal revealed that these hypoxia-related genes, which were the focus of the study, are linked to an unfavourable survival outcomes in prostate cancer patients

Differential Expression of Serum Proinflammatory Cytokine TNF-α and Genetic Determinants of TNF-α, CYP2C19*17, miR-423 Genes and Their Effect on Coronary Artery Disease Predisposition and Progression

Coronary artery disease (CAD) is the leading cause of death and hospitalization worldwide and represents a problem for public health systems everywhere. In Saudi Arabia, the prevalence of CAD is estimated to be 5.5%. Risk factors for CAD include older age, male gender, obesity, high blood pressure, smoking, diabetes, hyperlipidemia, and genetic factors. Reducing the risk factors in susceptible individuals will decrease the prevalence of CAD. Genome wide association studies have helped to reveal the association of many loci with diseases like CAD. In this study, we examined the link between single nucleotide variations (SNVs) of TNF-α-rs1800629 G>A, CYP2C19*17 (rs12248560) C>T, and miR-423 rs6505162 C>A and the expression of TNF-α with CAD. We used the mutation specific PCR, ARMS-PCR, and ELISA. The results showed that the A allele of the TNF-α rs1800629 G>A SNP is linked to CAD with odd ratio (OR) (95% CI) = 2.10, p-value = 0.0013. The T allele of the CYP2C19*17 (rs12248560) C>T is linked to CAD with OR (95% CI) = 2.02, p-value = 0.003. In addition, the A allele of the miR-423 rs6505162 C>A SNV is linked to CAD with OR (95% CI) = 1.49, p-value = 0.036. The ELISA results indicated that the TNF-α serum levels are significantly increased in CAD patients compared to healthy controls. We conclude the TNF-α rs1800629 G>A, CYP2C19*17, and miR-423 rs6505162 C>A are potential genetic loci for CAD in the Saudi population. These findings require further verification in future studies. After being verified, our results might be utilized in genetic testing to identify individuals that are susceptible to CAD and, therefore, for whom reducing modifiable risk factors (e.g., poor diet, diabetes, obesity, and smoking) would result in prevention or delay of CAD

In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes

Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein–protein interaction, and large-scale case–control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment