Regular Model Research Articles

Classification of HER2 status across multiple cancers using epigenomic profiles from a novel liquid biopsy assay.

3047 Background: The efficacy of trastuzumab deruxtecan in multiple cancers led to a recent FDA granting of priority review for the treatment of adults with HER2-positive solid tumors. This underscores the critical need for reliable assessment of HER2 expression across cancers. The current standard using IHC/ISH for HER2 scoring is fraught with challenges including scoring discordance and tumor heterogeneity. Here we describe the ability to classify HER2 status from 1 ml of plasma, using epigenomic signatures from a novel multi-analyte liquid biopsy (LBx) platform, offering a minimally invasive approach for patient (pt) selection across cancers. Methods: We selected 179 samples from 172 pts with advanced breast (BC), gastro-esophageal (GEA) and ovarian (OV) cancers who had associated HER2 status scored from tissue-based IHC/ISH according to ASCO/CAP guidelines (table). Samples were taken at baseline or at progression and those with detectable cell free DNA, as assessed by iChorCNA, were profiled for genome-wide epigenomic signals across histone modifications associated with active enhancers, promoters and DNA methylation. A regularized regression model developed to classify HER2 status in BC cell lines and was refined and validated for HER2 status prediction for each pt cohort (HER2+ = 3+, 2+/ISH+; HER2- = 2+/ISH-, 1+, 0). The BC cell-line derived HER2 classifier was refined to incorporate GEA and OV cancer specific features before being applied to those samples. Performance was assessed via AUC in a leave-one-out cross-validation schema. We also evaluated HER2 status at progression in a subset of pts with benchmarked HER2 IHC to assess dynamic changes in receptor status by LBx. Results: The epigenomic HER2 classifier was applied to all samples with ctDNA detectable by ichorCNA (90 of 179; 50%). HER2 classification of BC pts by epigenomic liquid biopsy was concordant with standard tissue-based IHC for 64/72 (89%) BC samples (AUC 0.9, table). HER2 classifier predictions for all longitudinally collected samples were concordant with IHC-based HER2 status, including the one patient whose status switched from HER2+ to HER2- at progression. Accurate classification of 11/14 (79%, GEA) and 4/4 (100%, OV) pts was achieved using the indication-refined HER2 classifier. Conclusions: We demonstrate proof of concept for a HER2 classification approach using comprehensive epigenomic signals from 1 ml of plasma that could be applied across multiple cancers. With further development, our genome-wide profiling approach could alleviate clinical constraints associated with multiple tissue-based HER2 scoring assays (IHC/ISH) and enable longitudinal monitoring of HER2 status on therapy. [Table: see text]

Guided regularization and its application for image restoration

Variational regularization, renowned for its sound theoretical foundations and impressive performance, is widely used in image restoration. The traditional regularization models typically use a predefined regularizer to promote smoothness in the solution. However, these models do not explicitly take into account any external information that should be preserved in the restoration. In this paper, we introduce a novel guided regularization model to enhance the efficacy of traditional regularization. Our model incorporates an external guidance regularizer, utilizing a guidance image to bolster the quality of restoration. By integrating this external information into the regularization process, the model is better equipped to preserve specific features or attributes indicated by the guidance image, leading to more accurate and aesthetically pleasing restored images. Furthermore, we demonstrate the convexity of the model and prove the existence and uniqueness of the solution. The alternating direction method of multipliers (ADMM) algorithm is employed to numerically solve the proposed model. In the experimental evaluation, the proposed model is applied to image denoising and deblurring tasks. The experiments successfully validate the proposed model and algorithm. Compared with several state-of-the-art models, the proposed model demonstrates the best performance in terms of peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM).

"Sweet space" strategy for solvent system selection in countercurrent chromatography: A case study on separation of polyunsaturated fatty acids from borage oil.

This study presents a comprehensive strategy for the selection and optimization of solvent systems in countercurrent chromatography (CCC) for the effective separation of compounds. With a focus on traditional organic solvent systems, the research introduces a "sweet space" strategy that merges intuitive understanding with mathematical accuracy, addressing the significant challenges in solvent system selection, a critical bottleneck in the widespread application of CCC. By employing a combination of volume ratios and graphical representations, including both regular and trirectangular tetrahedron models, the proposed approach facilitates a more inclusive and user-friendly strategy for solvent system selection. This study demonstrates the potential of the proposed strategy through the successful separation of gamma-linolenic acid, oleic acid, and linoleic acid from borage oil, highlighting the strategy's effectiveness and practical applicability in CCC separations.

Model selection for generalized linear models with weak factors

AbstractThe literature has witnessed an upsurge of interest in model selection in diverse fields and optimization applications. Despite the substantial progress, model selection remains a significant challenge when covariates are highly correlated, particularly within economic and financial datasets that exhibit cross‐sectional and serial dependency. In this paper, we introduce a novel methodology named factor augmented regularized model selection with weak factors (WeakFARM) for generalized linear models in the presence of correlated covariates with weak latent factor structure. By identifying weak latent factors and idiosyncratic components and employing them as predictors, WeakFARM converts the challenge from model selection with highly correlated covariates to that with weakly correlated ones. Furthermore, we develop a variable screening method based on the proposed WeakFARM method. Comprehensive theoretical guarantees including estimation consistency, model selection consistency and sure screening property are also provided. We demonstrate the effectiveness of our approach by extensive simulation studies and a real data application in economic forecasting.

The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features

IntroductionIncidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. MethodsAll patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. ResultsAmong the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38–60) for IGBC patients with no evidence of RD, compared to 31 months (23–42) for those with RD (p < 0.001). ConclusionRe-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.

OPTIMIZING HEART ATTACK DIAGNOSIS USING RANDOM FOREST WITH BAT ALGORITHM AND GREEDY CROSSOVER TECHNIQUE

Cardiovascular disease stands as one of the primary contributors to global mortality, with the World Health Organization (WHO) reporting approximately 17.9 million deaths annually. Swift and accurate diagnosis of heart attacks is crucial to ensure timely and specialized intervention for patients afflicted by this ailment. A machine learning algorithm that can be employed for addressing such issues is the Random Forest algorithm. However, the efficacy of the model is significantly influenced by the features selected during the training phase. To mitigate this, the Binary Bat Algorithm (BBA) with greedy crossover has been utilized to enhance feature selection within the model. This approach is particularly adept at preventing convergence issues often associated with local minima. The optimal parameters for BBA with greedy crossover are determined to be , , , and . With these parameters, the proposed algorithm identifies the most relevant features, including age, gender, cp, chol, thalach, oldpeak, slope, and ca, achieving an accuracy of 94.19% on the training data and 91.8% on the test data. Furthermore, the precision and recall values for both classes range from 0.87 to 0.96, contributing to an approximate -score of 0.92. The proposed method has increased its -score by 0.05 if compared with the regular Random Forest model. These results underscore the effectiveness of the proposed algorithm in providing accurate and reliable predictions for heart disease diagnosis. As such, this model makes diagnosing heart attack more convenient and effective because it does not require too much medical features or patient data. Hopefully, the results of this research help medical practitioners make better and timely decisions in the diagnosis and treatment of heart attacks, as well as assist in planning more effective public health programs for heart attack prevention.

Machine learning versus deep learning in land system science: a decision-making framework for effective land classification

This review explores the comparative utility of machine learning (ML) and deep learning (DL) in land system science (LSS) classification tasks. Through a comprehensive assessment, the study reveals that while DL techniques have emerged with transformative potential, their application in LSS often faces challenges related to data availability, computational demands, model interpretability, and overfitting. In many instances, traditional ML models currently present more effective solutions, as illustrated in our decision-making framework. Integrative opportunities for enhancing classification accuracy include data integration from diverse sources, the development of advanced DL architectures, leveraging unsupervised learning, and infusing domain-specific knowledge. The research also emphasizes the need for regular model evaluation, the creation of diversified training datasets, and fostering interdisciplinary collaborations. Furthermore, while the promise of DL for future advancements in LSS is undeniable, present considerations often tip the balance in favor of ML models for many classification schemes. This review serves as a guide for researchers, emphasizing the importance of choosing the right computational tools in the evolving landscape of LSS, to achieve reliable and nuanced land-use change data.

Blind deblurring text images via Beltrami regularization

This article proposes a blind image deblurring model based on Beltrami regularization. The existence and uniqueness of the Beltrami model are proved, and we perform a theoretical analysis of the convergence and error estimation of the algorithm for solving the Beltrami regularization model. Meanwhile, we apply a half-quadratic splitting algorithm to solve it and obtain the blur kernel of the blurred image. Furthermore, we get a clean image through some non-blind deblurring algorithms. Finally, we compare this with the state-of-art methods, and our algorithm has specific performance improvements and advantages in the text images.© 2024 Elsevier Ltd. All rights reserved.

Activity Calculation and Vacuum Separation Theoretical Research concerning Ag–Cu, Ag–Sb and Cu–Sb Binary Alloys

The Ag–Cu–Sb system is a key component of lead anode slime and boasts an exceptionally high economic recovery value. In this work, six models, including the Molecular Interaction Volume Model (MIVM), Modified Molecular Interaction Volume Model (M-MIVM), Wilson equation, Miedema model, Regular Solution Model (RSE) and Sub-Regular Solution Model (SRSE), are used to calculate the predicted values of the activity and its deviations with experimental data for binary alloys in the Ag–Cu–Sb system for the first time. The result reveals that the overall means of the average relative deviation and average standard deviation of the M-MIVM are 0.01501 and 3.97278%, respectively, which are about two to six times smaller than those of the other five models, indicating the stability and reliability of the M-MIVM. In the meantime, the predicted data of the Cu–Ag binary alloy at 1423 K, Sb–Ag binary alloy at 1250 K and Sb–Cu binary alloy at 1375 K calculated from the M-MIVM are more reliable and pass the Herington test. Then, the separation coefficient–composition (β–x), temperature–composition (T–x–y) and pressure–composition (P–x–y) of the Cu–Ag, Sb–Ag and Sb–Cu binary alloys are plotted based on the M-MIVM and vacuum theories, showing that the Cu–Ag binary alloy is relatively difficult to separate and that high temperatures or high copper contents are detrimental to obtaining high-purity silver. Meanwhile, theoretical data of the T–x–y diagram are consistent with the available experimental data. These results can guide vacuum separation experiments and industrial production concerning Ag–Cu, Ag–Sb and Cu–Sb binary alloys.

Eigenspectrum regularisation reverse neighbourhood discriminative learning

AbstractLinear discriminant analysis is a classical method for solving problems of dimensional reduction and pattern classification. Although it has been extensively developed, however, it still suffers from various common problems, such as the Small Sample Size (SSS) and the multimodal problem. Neighbourhood linear discriminant analysis (nLDA) was recently proposed to solve the problem of multimodal class caused by the contravention of independently and identically distributed samples. However, due to the existence of many small‐scale practical applications, nLDA still has to face the SSS problem, which leads to instability and poor generalisation caused by the singularity of the within‐neighbourhood scatter matrix. The authors exploit the eigenspectrum regularisation techniques to circumvent the singularity of the within‐neighbourhood scatter matrix of nLDA, which is called Eigenspectrum Regularisation Reverse Neighbourhood Discriminative Learning (ERRNDL). The algorithm of nLDA is reformulated as a framework by searching two projection matrices. Three eigenspectrum regularisation models are introduced to our framework to evaluate the performance. Experiments are conducted on the University of California, Irvine machine learning repository and six image classification datasets. The proposed ERRNDL‐based methods achieve considerable performance.

LSTM-Autoencoder Deep Learning Model for Anomaly Detection in Electric Motor

Anomaly detection is the process of detecting unusual or unforeseen patterns or events in data. Many factors, such as malfunctioning hardware, malevolent activities, or modifications to the data’s underlying distribution, might cause anomalies. One of the key factors in anomaly detection is balancing the trade-off between sensitivity and specificity. Balancing these trade-offs requires careful tuning of the anomaly detection algorithm and consideration of the specific domain and application. Deep learning techniques’ applications, such as LSTMs (long short-term memory algorithms), which are autoencoders for detecting an anomaly, have garnered increasing attention in recent years. The main goal of this work was to develop an anomaly detection solution for an electrical machine using an LSTM-autoencoder deep learning model. The work focused on detecting anomalies in an electrical motor’s variation vibrations in three axes: axial (X), radial (Y), and tangential (Z), which are indicative of potential faults or failures. The presented model is a combination of the two architectures; LSTM layers were added to the autoencoder in order to leverage the LSTM capacity for handling large amounts of temporal data. To prove the LSTM efficiency, we will create a regular autoencoder model using the Python programming language and the TensorFlow machine learning framework, and compare its performance with our main LSTM-based autoencoder model. The two models will be trained on the same database, and evaluated on three primary points: training time, loss function, and MSE anomalies. Based on the obtained results, it is clear that the LSTM-autoencoder shows significantly smaller loss values and MSE anomalies compared to the regular autoencoder. On the other hand, the regular autoencoder performs better than the LSTM, comparing the training time. It appears then, that the LSTM-autoencoder presents a superior performance although it was slower than the standard autoencoder due to the complexity of the added LSTM layers.

Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study

BackgroundThe value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT.MethodsPatients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI.ResultsIn total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1–6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18–4.52), cohort 2 (HR = 1.64, 95% CI: 1.26–2.14), cohort 3 (HR = 2.53, 95% CI: 1.45–4.3), cohort 4 (HR = 1.24, 95% CI: 1.01–1.52), cohort 5 (HR = 2.56, 95% CI: 0.73–9.02), cohort 6 (HR = 2.30, 95% CI: 0.53–10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60–0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50–0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46–0.70), and RPI (C-index: 0.65, 95% CI: 0.54–0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40–0.91; p = 0.02), while patients in the low-risk and high-risk groups did not.ConclusionsWe developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

Hyperspectral Image Mixed Noise Removal via Double Factor Total Variation Nonlocal Low-Rank Tensor Regularization

A hyperspectral image (HSI) is often corrupted by various types of noise during image acquisition, e.g., Gaussian noise, impulse noise, stripes, deadlines, and more. Thus, as a preprocessing step, HSI denoising plays a vital role in many subsequent tasks. Recently, a variety of mixed noise removal approaches have been developed for HSI, and the methods based on spatial–spectral double factor and total variation (DFTV) regularization have achieved comparable performance. Additionally, the nonlocal low-rank tensor model (NLR) is often employed to characterize spatial nonlocal self-similarity (NSS). Generally, fully exploring prior knowledge can improve the denoising performance, but it significantly increases the computational cost when the NSS prior is employed. To solve this problem, this article proposes a novel DFTV-based NLR regularization (DFTVNLR) model for HSI mixed noise removal. The proposed model employs low-rank tensor factorization (LRTF) to characterize the spectral global low-rankness (LR), introduces 2-D and 1-D TV constraints on double-factor to characterize the spatial and spectral local smoothness (LS), respectively. Meanwhile, the NLR is applied to the spatial factor to characterize the NSS. Then, we developed an algorithm based on proximal alternating minimization (PAM) to solve the proposed model effectively. Particularly, we effectively controlled the computational cost from two aspects, namely taking small-sized double factor as regularization object and putting the time-consuming NLR model before the main loop with fewer iterations to solve it independently. Finally, considerable experiments on simulated and real noisy HSI substantiate that the proposed method is superior to the related state-of-the-art methods in balancing the denoising effect and speed.

Heat flow topology-driven thermo-mass decoupling strategy: Cross-scale regularization modeling and optimization analysis

The liquid desiccant dehumidification (LDD) is both eco-friendly and highly effective in humidity control, widely investigated across diverse angles. This study expands the application of the newly devised heat current method to examine the liquid desiccant dehumidification process. It introduces a new regularized temperature, which includes using a heat flow topology driven thermo-mass decoupling strategy, and constructing the heat current model by defining both the thermal resistance and moisture resistance. It significantly extends the application of the heat current method, clarifying the thermo-mass coupling energy transfer mechanism. The findings indicate that key factors influencing system performance indicators include total thermal conductivity (αA), solution mass flow rate (ms), air-solution mass flow rate ratio (RA/S,D), and heat source temperature (tH). Furthermore, under the influence of distinct thermal conductivities, the optimal output values for performance indicators, including moisture removal rate, exergy efficiency and entransy efficiency, are determined as 8.4 g/s, 71.2%, and 12.3%, respectively. The results of synergistic influence analysis reveal that, for the performance indicator entransy efficiency, msand RA/S,D display a significant degree of synergistic influence, resulting in a strong positive effect and benefiting 68.53% of the total area. Multi-objective optimization indicates a trade-off relationship among the system performance evaluation indicators moisture removal rate, exergy efficiency and entransy efficiency, with optimal solution values of 3.25 g/s, 65.92%, and 12.01%, respectively.

Efficient image restoration via non-convex total variation regularization and ADMM optimization

This article presents a novel approach to image restoration utilizing a unique non-convex l1/2-TV regularization model. This model integrates the l1/2-quasi norm as a regularization function, introducing non-convexity to promote sparsity and unevenly penalize elements, thereby enhancing restoration outcomes. To tackle this model, an efficient algorithm named the Alternating Direction Method of Multipliers, based on the Lagrangian multiplier, is introduced. This effectively prevents the penalty parameter from reaching infinity and ensures excellent convergence behavior. The proposed algorithm decomposes the optimization problem into subproblems, for which closed-form solutions are derived, particularly addressing the challenging l1/2 regularization problem. To validate its effectiveness, a comprehensive set of experiments are conducted to compare its performance with existing methods. The experimental results demonstrate that the proposed model performs well in both qualitative and quantitative evaluations. Consequently, the proposed model is not only efficient and stable but also exhibits excellent convergence behavior.

Enhanced fracture risk prediction: a novel multi-trait genetic approach integrating polygenic scores of fracture-related traits

SummaryThe novel metaPGS, integrating multiple fracture–related genetic traits, surpasses traditional polygenic scores in predicting fracture risk. Demonstrating a robust association with incident fractures, this metaPGS offers significant potential for enhancing clinical fracture risk assessment and tailoring prevention strategies.IntroductionCurrent polygenic scores (PGS) have limited predictive power for fracture risk. To improve genetic prediction, we developed and evaluated a novel metaPGS combining genetic information from multiple fracture–related traits.MethodsWe derived individual PGS from genome-wide association studies of 16 fracture-related traits and employed an elastic-net logistic regression model to examine the association between the 16 PGSs and fractures. An optimal metaPGS was constructed by combining 11 significant individual PGSs selected by the elastic regularized regression model. We evaluated the predictive power of the metaPGS alone and in combination with clinical risk factors recommended by guidelines. The discrimination ability of metaPGS was assessed using the concordance index. Reclassification was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsThe metaPGS had a significant association with incident fractures (HR 1.21, 95% CI 1.18–1.25 per standard deviation of metaPGS), which was stronger than previously developed bone mineral density (BMD)-related individual PGSs. Models with PGS_FNBMD, PGS_TBBMD, and metaPGS had slightly higher but statistically non-significant c-index than the base model (0.640, 0.644, 0.644 vs. 0.638). However, the reclassification analysis showed that compared to the base model, the model with metaPGS improves the reclassification of fracture.ConclusionsThe metaPGS is a promising approach for stratifying fracture risk in the European population, improving fracture risk prediction by combining genetic information from multiple fracture–related traits.

Research on the method of determining the block size for an open-pit mine integrating mining parameters and shovel-truck’s operation efficiency

The production plan of an open-pit mine depends on the block model, so it's crucial to determine the appropriate method and size for partitioning it. This study proposes a new method based on a closed shell three-dimensional geological model for determining block model size in open-pit mines. Instead of using regular block models, the shell model is directly cut, and the discrete geological body is referred to as the "mining model." Mining parameters and the shovel-truck's performance are integrated into the method. Bench height determines the Z-axis size, bench slope angle determines the inclination angle, and shovel width determines the X-axis size of the block model. The operation efficiency of the shovel-truck considers the probability distribution of simultaneous operations, allowing the determination of the Y-axis size of block models for different types of shovels. The developed "Mining Model" module in the software "Life Cycle Mining System" is used for practical implementation. By comparing the results with traditional block models, the superiority of the proposed method is demonstrated. This study provides a more accurate model for optimizing the production plan of open-pit mines throughout their life cycle.

Negative variance components and intercept-slope correlations greater than one in magnitude: How do such "non-regular" random intercept and slope models arise, and what should be done when they do?

Statistical models with random intercepts and slopes (RIAS models) are commonly used to analyze longitudinal data. Fitting such models sometimes results in negative estimates of variance components or estimates on parameter space boundaries. This can be an unlucky chance occurrence, but can also occur because certain marginal distributions are mathematically identical to those from RIAS models with negative intercept and/or slope variance components and/or intercept-slope correlations greater than one in magnitude. We term such parameters "pseudo-variances" and "pseudo-correlations," and the models "non-regular." We use eigenvalue theory to explore how and when such non-regular RIAS models arise, showing: (i) A small number of measurements, short follow-up, and large residual variance increase the parameter space for which data (with a positive semidefinite marginal variance-covariance matrix) are compatible with non-regular RIAS models. (ii) Non-regular RIAS models can arise from model misspecification, when non-linearity in fixed effects is ignored or when random effects are omitted. (iii) A non-regular RIAS model can sometimes be interpreted as a regular linear mixed model with one or more additional random effects, which may not be identifiable from the data. (iv) Particular parameterizations of non-regular RIAS models have no generality for all possible numbers of measurements over time. Because of this lack of generality, we conclude that non-regular RIAS models can only be regarded as plausible data-generating mechanisms in some situations. Nevertheless, fitting a non-regular RIAS model can be acceptable, allowing unbiased inference on fixed effects where commonly recommended alternatives such as dropping the random slope result in bias.

Discovery and Validation of a 15-Gene Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Develop and validate gene expression-based biomarker associated with recurrent disease to facilitate risk stratification of clear cell renal cell carcinoma (ccRCC). We retrospectively identified 110 patients who underwent radical nephrectomy for ccRCC (discovery cohort). Patients who recurred were matched on the basis of grade/stage to patients without recurrence. Capture whole-transcriptome sequencing was performed on RNA isolated from archival tissue using the Illumina platform. We developed a gene-expression signature to predict recurrence-free survival/disease-free survival (DFS) using a 15-fold lasso and elastic-net regularized linear Cox model. We derived the 31-gene cell cycle progression (mxCCP) score using RNA-seq data for each patient. Kaplan-Meier (KM) curves and multivariable Cox proportional hazard testing were used to validate the independent prognostic impact of the gene-expression signature on DFS, disease-specific survival (DSS), and overall survival (OS) in two validation data sets (combined n = 761). After quality control, the discovery cohort comprised 50 patients with recurrence and 41 patients without, with a median follow-up of 26 and 36 months, respectively. We developed a 15-gene (15G) signature, which was independently associated with worse DFS and DSS (DFS: hazard ratio [HR], 11.08 [95% CI, 4.9 to 25.1]; DSS: HR, 9.67 [95% CI, 3.4 to 27.7]) in a multivariable model adjusting for clinicopathologic parameters (including stage, size, grade, and necrosis [SSIGN] score and Memorial Sloan Kettering Cancer Center nomogram) and mxCCP score. The 15G signature was also independently associated with worse DFS and DSS in both validation data sets (Validation A [n = 382], DFS: HR, 2.6 [95% CI, 1.6 to 4.3]; DSS: HR, 3 [95% CI, 1.4 to 6.1] and Validation B (n = 379), DFS: HR, 2.1 [95% CI, 1.2 to 3.6]; OS: HR, 3 [95% CI, 1.6 to 5.7]) adjusting for clinicopathologic variables and mxCCP score. We developed and validated a novel 15G prognostic signature to improve risk stratification of patients with ccRCC. Pending further validation, this signature has the potential to facilitate optimal treatment allocation.

Tweedie regularization model and application

This article proposes a new regular model called the Tweedie regular regression model. The Tweedie distributions are parameterized by their mean, dispersion and power parameter ξ. For each ξ, we obtain a specific regular model. Tweedie Regression model includes several distributions. In particular, for ξ = 0, we obtain the Gaussian case; the estimation of the parameters through the classical point of view has been done using Least Absolute Shrinkage and Selection Operator (Lasso), Ridge and Elastic methods. Therefore, the proposed model is appropriate for modeling equiover and underdispersed data. The parameters estimation, through the classical point of view, has been performed using the methods of Lasso, Ridge and Elastic approaches. The Tweedie regular regression model will be calibrated by choosing one of the Lasso, Ridge and Elastic approaches. To evaluate our suggested method, a detailed comparison study through a simulation and real data was conducted to verify the proposed models. It was carried out to examine the fitness of the estimated parameters. Compared with counterparts, the results demonstrate the superiority of models Ridge Tweedie Regression (RTR), Lasso Tweedie Regression (LTR), and Elastic Tweedie Regression (ETR) using MAE (Mean absolute error), RMSE (Root Mean Squared Error) and R-squared (Coefficient of determination)