A Novel Radiomics-Platelet Nomogram for the Prediction of Gastroesophageal Varices Needing Treatment in Cirrhotic Patients

Abstract Background and aimsHighly accurate noninvasive methods for predicting gastroesophageal varices needing treatment (VNT) are desired. Radiomics is a newly emerging technology of image analysis. This study aims to develop and validate a novel noninvasive method based on radiomics for predicting VNT in cirrhosis.MethodsIn this retrospective-prospective study, a total of 245 cirrhotic patients were divided as the training set, internal validation set and external validation set. Radiomics features were extracted from portal-phase computed tomography (CT) images of each patient. A radiomics signature (Rad-score) was constructed with the least absolute shrinkage and selection operator algorithm and 10-folds cross-validation in the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. ResultsThe rad-score, consisting of 14 features from the gastroesophageal region and 5 from the splenic hilum region, was effective for VNT classification. The diagnostic performance was further improved by combining the rad-score with platelet counts, achieving an AUC of 0.987(95% CI, 0.969-1.00), 0.973(95% CI, 0.939-1.00) and 0.947(95% CI, 0.876-1.00) in the training set, internal validation set and external validation set respectively. In efficacy and safety assessment, the radiomics nomogram could spare more than 40% of endoscopic examinations with a low risk of missing VNT (<5%), and no more than 8.3% of unnecessary endoscopic examinations still be performed.ConclusionsIn this study, we developed and validated a novel, diagnostic radiomics-based nomogram which is a reliable and noninvasive method to predict VNT in cirrhotic patients.

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Use of serum biomarkers in staging of canine hepatic fibrosis

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638719866881 ◽

2019 ◽

Vol 31 (5) ◽

pp. 665-673 ◽

Cited By ~ 1

Author(s):

Maud Menard ◽

Alexis Lecoindre ◽

Jean-Luc Cadoré ◽

Michèle Chevallier ◽

Aurélie Pagnon ◽

...

Keyword(s):

Liver Biopsy ◽

Hepatic Fibrosis ◽

External Validation ◽

Model Performance ◽

Area Under The Curve ◽

Gamma Glutamyl Transferase ◽

Training Set ◽

Internal Validation ◽

Validation Set ◽

Glutamyl Transferase

Accurate staging of hepatic fibrosis (HF) is important for treatment and prognosis of canine chronic hepatitis. HF scores are used in human medicine to indirectly stage and monitor HF, decreasing the need for liver biopsy. We developed a canine HF score to screen for moderate or greater HF. We included 96 dogs in our study, including 5 healthy dogs. A liver biopsy for histologic examination and a biochemistry profile were performed on all dogs. The dogs were randomly split into a training set of 58 dogs and a validation set of 38 dogs. A HF score that included alanine aminotransferase, alkaline phosphatase, total bilirubin, potassium, and gamma-glutamyl transferase was developed in the training set. Model performance was confirmed using the internal validation set, and was similar to the performance in the training set. The overall sensitivity and specificity for the study group were 80% and 70% respectively, with an area under the curve of 0.80 (0.71–0.90). This HF score could be used for indirect diagnosis of canine HF when biochemistry panels are performed on the Konelab 30i (Thermo Scientific), using reagents as in our study. External validation is required to determine if the score is sufficiently robust to utilize biochemical results measured in other laboratories with different instruments and methodologies.

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Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram

Frontiers in Oncology ◽

10.3389/fonc.2021.775079 ◽

2021 ◽

Vol 11 ◽

Author(s):

Aihua Wu ◽

Zhigang Liang ◽

Songbo Yuan ◽

Shanshan Wang ◽

Weidong Peng ◽

...

Keyword(s):

Pleural Effusion ◽

Diagnostic Accuracy ◽

Prediction Model ◽

Scoring System ◽

Malignant Pleural Effusion ◽

Diagnostic Performance ◽

External Validation ◽

Training Set ◽

Internal Validation ◽

Validation Set

BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.

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An Immune-Clinical Prognostic Index (ICPI) for Patients With De Novo Follicular Lymphoma Treated With R-CHOP/CHOP Chemotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.708784 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yaxiao Lu ◽

Jingwei Yu ◽

Wenchen Gong ◽

Liping Su ◽

Xiuhua Sun ◽

...

Keyword(s):

De Novo ◽

External Validation ◽

Prognostic Index ◽

Risk Groups ◽

Chop Chemotherapy ◽

Training Set ◽

Chi Square ◽

T Lymphocyte Subsets ◽

Internal Validation ◽

Validation Set

PurposeAlthough the role of tumor-infiltrating T cells in follicular lymphoma (FL) has been reported previously, the prognostic value of peripheral blood T lymphocyte subsets has not been systematically assessed. Thus, we aim to incorporate T-cell subsets with clinical features to develop a predictive model of clinical outcome.MethodsWe retrospectively screened a total of 1,008 patients, including 252 newly diagnosed de novo FL patients with available peripheral blood T lymphocyte subsets who were randomized to different sets (177 in the training set and 75 in the internal validation set). A nomogram and a novel immune-clinical prognostic index (ICPI) were established according to multivariate Cox regression analysis for progression-free survival (PFS). The concordance index (C-index), Akaike’s information criterion (AIC), and likelihood ratio chi-square were employed to compare the ICPI’s discriminatory capability and homogeneity to that of FLIPI, FLIPI2, and PRIMA-PI. Additional external validation was performed using a dataset (n = 157) from other four centers.ResultsIn the training set, multivariate analysis identified five independent prognostic factors (Stage III/IV disease, elevated lactate dehydrogenase (LDH), Hb <120g/L, CD4+ <30.7% and CD8+ >36.6%) for PFS. A novel ICPI was established according to the number of risk factors and stratify patients into 3 risk groups: high, intermediate, and low-risk with 4-5, 2-3, 0-1 risk factors respectively. The hazard ratios for patients in the high and intermediate-risk groups than those in the low-risk were 27.640 and 2.758. The ICPI could stratify patients into different risk groups both in the training set (P < 0.0001), internal validation set (P = 0.0039) and external validation set (P = 0.04). Moreover, in patients treated with RCHOP-like therapy, the ICPI was also predictive (P < 0.0001). In comparison to FLIPI, FLIPI2, and PRIMA-PI (C-index, 0.613-0.647), the ICPI offered adequate discrimination capability with C-index values of 0.679. Additionally, it exhibits good performance based on the lowest AIC and highest likelihood ratio chi-square score.ConclusionsThe ICPI is a novel predictive model with improved prognostic performance for patients with de novo FL treated with R-CHOP/CHOP chemotherapy. It is capable to be used in routine practice and guides individualized precision therapy.

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Retrained Classification of Tyrosinase Inhibitors and “In Silico” Potency Estimation by Using Atom-Type Linear Indices

Methodologies and Applications for Chemoinformatics and Chemical Engineering ◽

10.4018/978-1-4666-4010-8.ch021 ◽

2013 ◽

pp. 322-427

Keyword(s):

External Validation ◽

Correlation Coefficients ◽

Classification Models ◽

Training Set ◽

Linear Discriminant ◽

Oecd Principles ◽

Qsar Models ◽

Validation Set ◽

Global Accuracy

In this paper, the authors present an effort to increase the applicability domain (AD) by means of retraining models using a database of 701 great dissimilar molecules presenting anti-tyrosinase activity and 728 drugs with other uses. Atom-based linear indices and best subset linear discriminant analysis (LDA) were used to develop individual classification models. Eighteen individual classification-based QSAR models for the tyrosinase inhibitory activity were obtained with global accuracy varying from 88.15-91.60% in the training set and values of Matthews correlation coefficients (C) varying from 0.76-0.82. The external validation set shows globally classifications above 85.99% and 0.72 for C. All individual models were validated and fulfilled by OECD principles. A brief analysis of AD for the training set of 478 compounds and the new active compounds included in the re-training was carried out. Various assembled multiclassifier systems contained eighteen models using different selection criterions were obtained, which provide possibility of select the best strategy for particular problem. The various assembled multiclassifier systems also estimated the potency of active identified compounds. Eighteen validated potency models by OECD principles were used.

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Multiclass Classifier for P-Glycoprotein Substrates, Inhibitors, and Non-Active Compounds

Molecules ◽

10.3390/molecules24102006 ◽

2019 ◽

Vol 24 (10) ◽

pp. 2006 ◽

Cited By ~ 1

Author(s):

Liadys Mora Lagares ◽

Nikola Minovski ◽

Marjana Novič

Keyword(s):

In Silico ◽

Transmembrane Protein ◽

External Validation ◽

Assessment Process ◽

Classification Model ◽

Training Set ◽

Test Set ◽

Active Compounds ◽

P Glycoprotein ◽

Validation Set

P-glycoprotein (P-gp) is a transmembrane protein that actively transports a wide variety of chemically diverse compounds out of the cell. It is highly associated with the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties of drugs/drug candidates and contributes to decreasing toxicity by eliminating compounds from cells, thereby preventing intracellular accumulation. Therefore, in the drug discovery and toxicological assessment process it is advisable to pay attention to whether a compound under development could be transported by P-gp or not. In this study, an in silico multiclass classification model capable of predicting the probability of a compound to interact with P-gp was developed using a counter-propagation artificial neural network (CP ANN) based on a set of 2D molecular descriptors, as well as an extensive dataset of 2512 compounds (1178 P-gp inhibitors, 477 P-gp substrates and 857 P-gp non-active compounds). The model provided a good classification performance, producing non error rate (NER) values of 0.93 for the training set and 0.85 for the test set, while the average precision (AvPr) was 0.93 for the training set and 0.87 for the test set. An external validation set of 385 compounds was used to challenge the model’s performance. On the external validation set the NER and AvPr values were 0.70 for both indices. We believe that this in silico classifier could be effectively used as a reliable virtual screening tool for identifying potential P-gp ligands.

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Serum microRNA signatures for the detection of pancreatobiliary cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15718 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15718-e15718

Author(s):

Shuichi Mitsunaga ◽

Shogo Nomura ◽

Kazuo Hara ◽

Yukiko Takayama ◽

Makoto Ueno ◽

...

Keyword(s):

Validation Cohort ◽

External Validation ◽

Diagnostic Value ◽

Healthy Controls ◽

Mirna Signature ◽

Training Set ◽

Linear Discriminant ◽

Serum Mirna ◽

Validation Set ◽

Sensitivity Specificity

e15718 Background: The diagnostic value of serum microRNAs (miRNA) in a highly sensitive microarray for pancreatobiliary cancer (PBca) has been demonstrated. This study attempted to build and validate a signature comprised of multiple serum miRNA markers for discriminating PBca from healthy controls. Methods: A multicenter prospective study on the diagnostic performance of serum miRNAs was conducted. The patients (pts) with treatment-naïve PBca and healthy participants aged ≥60 years were enrolled. Clinical data and sera were collected. Target population was randomly divided to training or validation cohort with an allocation ratio of 2:1. Twenty-nine serum miRNA markers on the microarray data were analyzed. Using any combinations of the markers, a Fisher’s linear discriminant analysis was performed, and the resulting sensitivity, specificity and AUC of ROC curve to discriminate PBca from healthy controls were calculated for each combination. Marker combinations with a sensitivity/specificity (SN/SP) of ≥80%/90% and high AUC in comparison with AUC of CA19-9 were defined as the diagnostic miRNA signature, which were selected in the training cohort. Next, the signatures were screened out which showed a good reproducibility in the validation cohort. As an independent external cohort, PBca pts and healthy with pooled frozen sera were enrolled and the identified miRNA signatures were further validated. Results: Total of 546 participants (80 healthy and 223 PBca in training set, 40 healthy and 104 PBca in validation set, 49 healthy and 50 PBca in external validation set) were analyzed in this study. Four serum miRNA combinations were identified as the diagnostic miRNA signature. In the training set, four miRNA signatures, consisted of 10 miRNAs, were developed. For the best-performed miRNA signature, the SN/SP and AUC in the validation and external validation cohorts were 84/90% and 0.95 (CA19-9: 73/95% and 0.88) and 84/90% and 0.93 (CA19-9: 80/94% and 0.87), respectively. Conclusions: The diagnostic serum miRNA signatures for PBca were identified in this study.

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Establishment and Validation of a Clinically Predictive Nomogram Model for Thyroid Carcinoma Patients

10.21203/rs.3.rs-123528/v1 ◽

2020 ◽

Author(s):

Ruyi Zhang ◽

Mei Xu ◽

Xiangxiang Liu ◽

Miao Wang ◽

Qiang Jia ◽

...

Keyword(s):

Thyroid Carcinoma ◽

External Validation ◽

Cancer Staging ◽

Curve Analysis ◽

Calibration Plot ◽

Net Benefit ◽

Training Set ◽

Decision Curve Analysis ◽

Validation Set ◽

Good Calibration

Abstract Objectives To develop a clinically predictive nomogram model which can maximize patients’ net benefit in terms of predicting the prognosis of patients with thyroid carcinoma based on the 8th edition of the AJCC Cancer Staging method. MethodsWe selected 134,962 thyroid carcinoma patients diagnosed between 2004 and 2015 from SEER database with details of the 8th edition of the AJCC Cancer Staging Manual and separated those patients into two datasets randomly. The first dataset, training set, was used to build the nomogram model accounting for 80% (94,474 cases) and the second dataset, validation set, was used for external validation accounting for 20% (40,488 cases). Then we evaluated its clinical availability by analyzing DCA (Decision Curve Analysis) performance and evaluated its accuracy by calculating AUC, C-index as well as calibration plot.ResultsDecision curve analysis showed the final prediction model could maximize patients’ net benefit. In training set and validation set, Harrell’s Concordance Indexes were 0.9450 and 0.9421 respectively. Both sensitivity and specificity of three predicted time points (12 Months,36 Months and 60 Months) of two datasets were all above 0.80 except sensitivity of 60-month time point of validation set was 0.7662. AUCs of three predicted timepoints were 0.9562, 0.9273 and 0.9009 respectively for training set. Similarly, those numbers were 0.9645, 0.9329, and 0.8894 respectively for validation set. Calibration plot also showed that the nomogram model had a good calibration.ConclusionThe final nomogram model provided with both excellent accuracy and clinical availability and should be able to predict patients’ survival probability visually and accurately.

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An adapted neural-fuzzy inference system model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in patients after heart valve replacement

10.21203/rs.3.rs-224969/v1 ◽

2021 ◽

Author(s):

Zhi-Chun Gu ◽

Shou-Rui Huang ◽

Dong Li ◽

Qin Zhou ◽

Jing Wang ◽

...

Keyword(s):

Fuzzy Inference ◽

Predictive Accuracy ◽

External Validation ◽

High Dose ◽

Internal Validation ◽

Inference System ◽

Dose Warfarin ◽

The Mean ◽

Balanced Model ◽

Validation Set

Abstract Background Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and huge inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). Methods This retrospective study enrolled patients who underwent HVR between June 1, 2012 and June 1, 2016 from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose, and the models’ predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general liner model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). Results A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2,820 in the balanced training set; 1,511 in the internal validation set; and 1,511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage: 74.39–78.16%, MAE: 0.37 mg/daily, MSE: 0.39 mg/daily) and the balanced model (ideal prediction percentage: 73.46–75.31%, MAE: 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. Conclusions The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.

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Construction and validation of a 6-gene nomogram discriminating lung metastasis risk of breast cancer patients

PLoS ONE ◽

10.1371/journal.pone.0244693 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244693

Author(s):

Lingchen Wang ◽

Wenhua Wang ◽

Shaopeng Zeng ◽

Huilie Zheng ◽

Quqin Lu

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Lung Metastasis ◽

Cancer Metastasis ◽

External Validation ◽

Breast Cancer Patients ◽

Training Set ◽

Validation Set ◽

Robust Likelihood ◽

Six Genes

Breast cancer is the most common malignant disease in women. Metastasis is the foremost cause of death. Breast tumor cells have a proclivity to metastasize to specific organs. The lung is one of the most common sites of breast cancer metastasis. Therefore, we aimed to build a useful and convenient prediction tool based on several genes that may affect lung metastasis-free survival (LMFS). We preliminarily identified 319 genes associated with lung metastasis in the training set GSE5327 (n = 58). Enrichment analysis of GO functions and KEGG pathways was conducted based on these genes. The best genes for modeling were selected using a robust likelihood-based survival modeling approach: GOLGB1, TMEM158, CXCL8, MCM5, HIF1AN, and TSPAN31. A prognostic nomogram for predicting lung metastasis in breast cancer was developed based on these six genes. The effectiveness of the nomogram was evaluated in the training set GSE5327 and the validation set GSE2603. Both the internal validation and the external validation manifested the effectiveness of our 6-gene prognostic nomogram in predicting the lung metastasis risk of breast cancer patients. On the other hand, in the validation set GSE2603, we found that neither the six genes in the nomogram nor the risk predicted by the nomogram were associated with bone metastasis of breast cancer, preliminarily suggesting that these genes and nomogram were specifically associated with lung metastasis of breast cancer. What’s more, five genes in the nomogram were significantly differentially expressed between breast cancer and normal breast tissues in the TIMER database. In conclusion, we constructed a new and convenient prediction model based on 6 genes that showed practical value in predicting the lung metastasis risk for clinical breast cancer patients. In addition, some of these genes could be treated as potential metastasis biomarkers for antimetastatic therapy in breast cancer. The evolution of this nomogram will provide a good reference for the prediction of tumor metastasis to other specific organs.

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