Salivary Metabolomics for Prognosis of Oral Squamous Cell Carcinoma

This study aimed to identify salivary metabolomic biomarkers for predicting the prognosis of oral squamous cell carcinoma (OSCC) based on comprehensive metabolomic analyses. Quantified metabolomics data of unstimulated saliva samples collected from patients with OSCC (n = 72) were randomly divided into the training (n = 35) and validation groups (n = 37). The training data were used to develop a Cox proportional hazards regression model for identifying significant metabolites as prognostic factors for overall survival (OS) and disease-free survival. Moreover, the validation group was used to develop another Cox proportional hazards regression model using the previously identified metabolites. There were no significant between-group differences in the participants’ characteristics, including age, sex, and the median follow-up periods (55 months [range: 3–100] vs. 43 months [range: 0–97]). The concentrations of 5-hydroxylysine (p = 0.009) and 3-methylhistidine (p = 0.012) were identified as significant prognostic factors for OS in the training group. Among them, the concentration of 3-methylhistidine was a significant prognostic factor for OS in the validation group (p = 0.048). Our findings revealed that salivary 3-methylhistidine is a prognostic factor for OS in patients with OSCC.

Single-Photon Emission Computed Tomography/Computed Tomography Image-Based Radiomics for Discriminating Vertebral Bone Metastases From Benign Bone Lesions in Patients With Tumors

Purpose: The purpose of this study was to investigate the feasibility of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) image-based radiomics in differentiating bone metastases from benign bone lesions in patients with tumors.Methods: A total of 192 lesions from 132 patients (134 in the training group, 58 in the validation group) diagnosed with vertebral bone metastases or benign bone lesions were enrolled. All images were evaluated and diagnosed independently by two physicians with more than 20 years of diagnostic experience for qualitative classification, the images were imported into MaZda software in Bitmap (BMP) format for feature extraction. All radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation algorithms after the process of normalization and correlation analysis. Based on these selected features, two models were established: The CT model and SPECT model (radiomics features were derived from CT and SPECT images, respectively). In addition, a combination model (ComModel) combined CT and SPECT features was developed in order to better evaluate the predictive performance of radiomics models. Subsequently, the diagnostic performance between each model was separately evaluated by a confusion matrix.Results: There were 12, 13, and 18 features contained within the CT, SPECT, and ComModel, respectively. The constructed radiomics models based on SPECT/CT images to discriminate between bone metastases and benign bone lesions not only had high diagnostic efficacy in the training group (AUC of 0.894, 0.914, 0.951 for CT model, SPECT model, and ComModel, respectively), but also performed well in the validation group (AUC; 0.844, 0.871, 0.926). The AUC value of the human experts was 0.849 and 0.839 in the training and validation groups, respectively. Furthermore, both SPECT model and ComModel show higher classification performance than human experts in the training group (P = 0.021 and P = 0.001, respectively) and the validation group (P = 0.037 and P = 0.007, respectively). All models showed better diagnostic accuracy than human experts in the training group and the validation group.Conclusion: Radiomics derived from SPECT/CT images could effectively discriminate between bone metastases and benign bone lesions. This technique may be a new non-invasive way to help prevent unnecessary delays in diagnosis and a potential contribution in disease staging and treatment planning.

Validation and modification of HEART score components for patients with chest pain in the emergency department

Objective This study aimed to clarify the relative prognostic value of each History, Electrocardiography, Age, Risk Factors, and Troponin (HEART) score component for major adverse cardiac events (MACE) within 3 months and validate the modified HEART (mHEART) score.Methods This study evaluated the HEART score components for patients with chest symptoms visiting the emergency department from November 19, 2018 to November 19, 2019. All components were evaluated using logistic regression analysis and the scores for HEART, mHEART, and Thrombolysis in Myocardial Infarction (TIMI) were determined using the receiver operating characteristics curve.Results The patients were divided into a derivation (809 patients) and a validation group (298 patients). In multivariate analysis, age did not show statistical significance in the detection of MACE within 3 months and the mHEART score was calculated after omitting the age component. The areas under the receiver operating characteristics curves for HEART, mHEART and TIMI scores in the prediction of MACE within 3 months were 0.88, 0.91, and 0.83, respectively, in the derivation group; and 0.88, 0.91, and 0.81, respectively, in the validation group. When the cutoff value for each scoring system was determined for the maintenance of a negative predictive value for a MACE rate >99%, the mHEART score showed the highest sensitivity, specificity, positive predictive value, and negative predictive value (97.4%, 54.2%, 23.7%, and 99.3%, respectively).Conclusion Our study showed that the mHEART score better detects short-term MACE in high-risk patients and ensures the safe disposition of low-risk patients than the HEART and TIMI scores.

Evaluation of Microvascular Patterns Alone Using Endocytoscopy with Narrow-Band Imaging for Diagnosing Gastric Cancer

<b><i>Introduction:</i></b> Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI. <b><i>Methods:</i></b> Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed “irregular.” The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance. <b><i>Results:</i></b> In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, <i>p</i> &#x3c; 0.0001 and 92.5% vs. 67.5%, <i>p</i> &#x3c; 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, <i>p</i> &#x3c; 0.0001 and 89.5% vs. 38.6%, <i>p</i> &#x3c; 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns. <b><i>Discussion/Conclusion:</i></b> Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice.

Identification of Immune-Related Genes Associated With Bladder Cancer Based on Immunological Characteristics and Their Correlation With the Prognosis

Background:To identify the immune-related genes of bladder cancer (BLCA) based on immunological characteristics and explore their correlation with the prognosis. Methods:We downloaded the gene and clinical data of BLCA from the Cancer Genome Atlas (TCGA) as the training group, and obtained immune-related genes from the Immport database. We downloaded GSE31684 and GSE39281 from the Gene Expression Omnibus (GEO) as the external validation group. R (version 4.0.5) and Perl were used to analyze all data. Result:Univariate Cox regression analysis and Lasso regression analysis revealed that 9 prognosis-related immunity genes (PIMGs) of differentially expressed immune genes (DEIGs) were significantly associated with the survival of BLCA patients (p &lt; 0.01), of which 5 genes, including NPR2, PDGFRA, VIM, RBP1, RBP1 and TNC, increased the risk of the prognosis, while the rest, including CD3D, GNLY, LCK, and ZAP70, decreased the risk of the prognosis. Then, we used these genes to establish a prognostic model. We drew receiver operator characteristic (ROC) curves in the training group, and estimated the area under the curve (AUC) of 1-, 3- and 5-year survival for this model, which were 0.688, 0.719, and 0.706, respectively. The accuracy of the prognostic model was verified by the calibration chart. Combining clinical factors, we established a nomogram. The ROC curve in the external validation group showed that the nomogram had a good predictive ability for the survival rate, with a high accuracy, and the AUC values of 1-, 3-, and 5-year survival were 0.744, 0.770, and 0.782, respectively. The calibration chart indicated that the nomogram performed similarly with the ideal model. Conclusion:We had identified nine genes, including PDGFRA, VIM, RBP1, RBP1, TNC, CD3D, GNLY, LCK, and ZAP70, which played important roles in the occurrence and development of BLCA. The prognostic model based on these genes had good accuracy in predicting the OS of patients and might be promising candidates of therapeutic targets. This study may provide a new insight for the diagnosis, treatment and prognosis of BLCA from the perspective of immunology. However, further experimental studies are necessary to reveal the underlying mechanisms by which these genes mediate the progression of BLCA.

Development and Validation of a Predictive Model to Evaluate the Risk of Bone Metastasis in Kidney Cancer

BackgroundBone is a common target of metastasis in kidney cancer, and accurately predicting the risk of bone metastases (BMs) facilitates risk stratification and precision medicine in kidney cancer.MethodsPatients diagnosed with kidney cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to comprise the training group from 2010 to 2017, and the validation group was drawn from our academic medical center. Univariate and multivariate logistic regression analyses explored the statistical relationships between the included variables and BM. Statistically significant risk factors were applied to develop a nomogram. Calibration plots, receiver operating characteristic (ROC) curves, probability density functions (PDF), and clinical utility curves (CUC) were used to verify the predictive performance. Kaplan-Meier (KM) curves demonstrated survival differences between two subgroups of kidney cancer with and without BMs. A convenient web calculator was provided for users via “shiny” package.ResultsA total of 43,503 patients were recruited in this study, of which 42,650 were training group cases and 853 validation group cases. The variables included in the nomogram were sex, pathological grade, T-stage, N-stage, sequence number, brain metastases, liver metastasis, pulmonary metastasis, histological type, primary site, and laterality. The calibration plots confirmed good agreement between the prediction model and the actual results. The area under the curve (AUC) values in the training and validation groups were 0.952 (95% CI, 0.950–0.954) and 0.836 (95% CI, 0.809–0.860), respectively. Based on CUC, we recommend a threshold probability of 5% to guide the diagnosis of BMs.ConclusionsThe comprehensive predictive tool consisting of nomogram and web calculator contributes to risk stratification which helped clinicians identify high-risk cases and provide personalized treatment options.

Multiparametric MRI Radiomics for the Early Prediction of Response to Chemoradiotherapy in Patients With Postoperative Residual Gliomas: An Initial Study

PurposeTo evaluate whether multiparametric magnetic resonance imaging (MRI)-based logistic regression models can facilitate the early prediction of chemoradiotherapy response in patients with residual brain gliomas after surgery.Patients and MethodsA total of 84 patients with residual gliomas after surgery from January 2015 to September 2020 who were treated with chemoradiotherapy were retrospectively enrolled and classified as treatment-sensitive or treatment-insensitive. These patients were divided into a training group (from institution 1, 57 patients) and a validation group (from institutions 2 and 3, 27 patients). All preoperative and postoperative MR images were obtained, including T1-weighted (T1-w), T2-weighted (T2-w), and contrast-enhanced T1-weighted (CET1-w) images. A total of 851 radiomics features were extracted from every imaging series. Feature selection was performed with univariate analysis or in combination with multivariate analysis. Then, four multivariable logistic regression models derived from T1-w, T2-w, CET1-w and Joint series (T1+T2+CET1-w) were constructed to predict the response of postoperative residual gliomas to chemoradiotherapy (sensitive or insensitive). These models were validated in the validation group. Calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were applied to compare the predictive performances of these models.ResultsFour models were created and showed the following areas under the ROC curves (AUCs) in the training and validation groups: Model-Joint series (AUC, 0.923 and 0.852), Model-T1 (AUC, 0.835 and 0.809), Model-T2 (AUC, 0.784 and 0.605), and Model-CET1 (AUC, 0.805 and 0.537). These results indicated that the Model-Joint series had the best performance in the validation group, followed by Model-T1, Model-T2 and finally Model-CET1. The calibration curves indicated good agreement between the Model-Joint series predictions and actual probabilities. Additionally, the DCA curves demonstrated that the Model-Joint series was clinically useful.ConclusionMultiparametric MRI-based radiomics models can potentially predict tumor response after chemoradiotherapy in patients with postoperative residual gliomas, which may aid clinical decision making, especially to help patients initially predicted to be treatment-insensitive avoid the toxicity of chemoradiotherapy.

A novel model to predict mental distress among medical graduate students in China

Background Poor mental health was reported among medical graduate students in some studies. Identification of risk factors for predicting the mental health is capable of reducing psychological distress among medical graduate students. Therefore, the aim of the study was to identify potential risk factors relating to mental health and further create a novel prediction model to calculate the risk of mental distress among medical graduate students. Methods This study collected and analyzed 1079 medical graduate students via an online questionnaire. Included participants were randomly classified into a training group and a validation group. A model was developed in the training group and validation of the model was performed in the validation group. The predictive performance of the model was assessed using the discrimination and calibration. Results One thousand and fifteen participants were enrolled and then randomly divided into the training group (n = 508) and the validation group (n = 507). The prevalence of severe mental distress was 14.96% in the training group, and 16.77% in the validation group. The model was developed using the six variables, including the year of study, type of student, daily research time, monthly income, scientific learning style, and feeling of time stress. The area under the receiver operating characteristic curve (AUROC) and calibration slope for the model were 0.70 and 0.90 (95% CI: 0.65 ~ 1.15) in the training group, respectively, and 0.66 and 0.80 (95% CI, 0.51 ~ 1.09) in the validation group, respectively. Conclusions The study identified six risk factors for predicting anxiety and depression and successfully created a prediction model. The model may be a useful tool that can identify the mental status among medical graduate students. Trial registration No.ChiCTR2000039574, prospectively registered on 1 November 2020.

A Combined Nomogram Model to Predict Disease-free Survival in Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy

Background: To investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS.Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation.Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (p&lt;0.001) and was validated in the external validation group. Multivariate analysis identified three independent indicators: multifocal/centric disease status, pCR status, and Rad-score. A nomogram based on these factors showed discriminatory ability, the C-index of the model was 0.834 (95% CI, 0.761–0.907) and 0.868 (95% CI, 0.787–949) in the training and the validation groups, respectively, which is better than clinicoradiological nomogram(training group: C-index = 0.726, 95% CI = 0.709–0.743; validation group: C-index = 0.774,95% CI = 0.743–0.805).Conclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.

PPARG, GNG12, and CD19 are Potential Independent Predictors of Central Nerve Recurrence in Childhood Acute Lymphoblastic Leukemia

Objective: To identify biomarkers that can predict the recurrence of the central nervous system (CNS) in children with acute lymphoblastic leukemia (ALL), and establish a prediction model. Materials and Methods: The transcriptome and clinical data collected by the Children's Oncology Group (COG) collaboration group in the Phase II study (use for test group) and Phase I study (use for validation group) of ALL in children were downloaded from the TARGET database. Transcriptome data were analyzed by bioinformatics method to identify core (hub) genes and establish a risk assessment model. Univariate Cox analysis was performed on each clinical data, and multivariate Cox regression analysis was performed on the obtained results and risk score. The children ALL phase I samples collected by the COG collaboration group in the TARGET database were used for verification. Results: A total of 1230 differentially expressed genes were screened out between the CNS relapsed and non-relapsed groups. Univariate multivariate Cox analysis of 10 hub genes identified showed that PPARG (HR=0.78, 95%CI=0.67-0.91, p=0.007), CD19 (HR=1.15, 95%CI=1.05-1.26, p=0.003) and GNG12 (HR=1.25, 95%CI=1.04-1.51, p=0.017) had statistical differences. The risk score was statistically significant in univariate (HR=3.06, 95%CI=1.30-7.19, p=0.011) and multivariate (HR=1.81, 95%CI=1.16-2.32, p=0.046) Cox regression analysis. The survival analysis results of the high and low-risk groups were different when the validation group was substituted into the model (p=0.018). In addition, the CNS involvement grading status at first diagnosis CNS3 vs. CNS1 (HR=5.74, 95%CI=2.01-16.4, p=0.001), T cell vs B cell (HR=1.63, 95% CI=1.06-2.49, p=0.026) were also statistically significant. Conclusions: PPARG, GNG12, and CD19 may be predictors of CNS relapse in childhood ALL.