Biological underpinnings of radiomic magnetic resonance imaging phenotypes for risk stratification in IDH wild-type glioblastoma
Fangzhan GuanZilong WangYuning QiuYu GuoDongling PeiMinkai WangAoqi XingZhongyi LiuBin YuJingliang ChengXianzhi LiuYuchen JiDongming YanJing YanZhenyu Zhang
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Abstract Background To develop and validate a conventional MRI-based radiomic model for predicting prognosis in patients with IDH wild-type glioblastoma (GBM) and reveal the biological underpinning of the radiomic phenotypes. Methods A total of 801 adult patients (training set, N = 471; internal validation set, N = 239; external validation set, N = 91) diagnosed with IDH wild-type GBM were included. A 20-feature radiomic risk score (Radscore) was built for overall survival (OS) prediction by univariate prognostic analysis and least absolute shrinkage and selection operator (LASSO) Cox regression in the training set. GSEA and WGCNA were applied to identify the intersectional pathways underlying the prognostic radiomic features in a radiogenomic analysis set with paired MRI and RNA-seq data (N = 132). The biological meaning of the conventional MRI sequences was revealed using a Mantel test. Results Radscore was demonstrated to be an independent prognostic factor (P < 0.001). Incorporating the Radscore into a clinical model resulted in a radiomic-clinical nomogram predicting survival better than either the Radscore model or the clinical model alone, with better calibration and classification accuracy (a total net reclassification improvement of 0.403, P < 0.001). Three pathway categories (proliferation, DNA damage response, and immune response) were significantly correlated with the prognostic radiomic phenotypes. Conclusion Our findings indicated that the prognostic radiomic phenotypes derived from conventional MRI are driven by distinct pathways involved in proliferation, DNA damage response, and immunity of IDH wild-type GBM.Keywords:
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Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i) full model using all available predictors and estimated by standard techniques, (ii) backward elimination (BE), (iii) ridge regression, (iv) least absolute shrinkage and selection operator (lasso), and (v) elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD), we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches. Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.
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Abstract This 1:5 case‐control study aimed to identify the risk factors of hospital‐acquired pressure injuries (HAPIs) and to develop a mathematical model of nomogram for the risk prediction of HAPIs. Data for 370 patients with HAPIs and 1971 patients without HAPIs were extracted from the adverse events and the electronic medical systems. They were randomly divided into two sets: training (n = 1951) and validation (n = 390). Significant risk factors were identified by univariate and multivariate analyses in the training set, followed by a nomogram constructed. Age, independent movement, sensory perception and response, moisture, perfusion, use of medical devices, compulsive position, hypoalbuminaemia, an existing pressure injury or scarring from a previous pressure injury, and surgery sufferings were considered significant risk factors and were included to construct a nomogram. In both of the training and validation sets, the areas of 0.90 under the receiver operating characteristic curves showed excellent discrimination of the nomogram; calibration plots demonstrated a good consistency between the observed probability and the nomogram's prediction; decision curve analyses exhibited preferable net benefit along with the threshold probability in the nomogram. The excellent performance of the nomogram makes it a convenient and reliable tool for the risk prediction of HAPIs.
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Objective: To compare the diagnostic accuracy of various transcutaneous bilirubin (TcB) nomograms for predischarge screening. Methods: The paired total serum bilirubin (TSB) and TcB measurements collected in neonates ≥35 weeks and ≥2000 g birth weight were analyzed. BiliCare™ bilirubinometer was used for TcB measurement. We chose the following nomograms for the study: Bhutani nomogram, Maisel's nomogram, Agarwal nomogram, Thakkar nomogram, American Academy of Pediatrics (AAP) nomogram within 3 mg/dl of phototherapy cutoff, AAP nomogram >70% of phototherapy cutoff and if TcB value is above 13 mg/dl. The diagnostic accuracy of these nomograms for TcB was compared with TSB plotted in the Bhutani nomogram. Results: TcB showed a positive correlation with TSB (Pearson correlation coefficient = 0.783). Bhutani nomogram, Maisel's nomogram and AAP (using within 3 mg/dL cutoff) nomogram showed good sensitivity and low false-negative rate while avoiding blood draws in most neonates. Conclusion: Bhutani nomogram, Maisel's nomogram, and AAP (using within 3 mg/dL of phototherapy cutoff) nomograms have comparable diagnostic accuracy for predischarge bilirubin screening in neonates.
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Conducting an extensive empirical study on short-term electricity price forecasting (EPF), involving state-of-the-art parsimonious expert models as benchmarks, datasets from 12 power markets and 32 multi-parameter regression models estimated via the lasso, we show that using the latter shrinkage approach can bring statistically significant accuracy gains compared to commonly-used EPF models. We also address the long-standing question on the optimal model structure for EPF. We provide evidence that despite a minor edge in predictive performance overall, the multivariate modeling approach does not uniformly outperform univariate models across all datasets, seasons of the year or hours of the day, and at times is outperformed by the latter. This may be an indication that combining advanced structures or the corresponding forecasts from both modeling classes may bring a further improvement in forecasting accuracy. Finally, we also analyze variable selection for the best performing multivariate and univariate high-dimensional lasso-type models, thus provide guidelines to structuring better performing forecasting model designs.
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