Machine Learning Prediction Model for Acute Renal Failure After Acute Aortic Syndrome Surgery

BackgroundAcute renal failure (ARF) is the most common major complication following cardiac surgery for acute aortic syndrome (AAS) and worsens the postoperative prognosis. Our aim was to establish a machine learning prediction model for ARF occurrence in AAS patients.MethodsWe included AAS patient data from nine medical centers (n = 1,637) and analyzed the incidence of ARF and the risk factors for postoperative ARF. We used data from six medical centers to compare the performance of four machine learning models and performed internal validation to identify AAS patients who developed postoperative ARF. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to compare the performance of the predictive models. We compared the performance of the optimal machine learning prediction model with that of traditional prediction models. Data from three medical centers were used for external validation.ResultsThe eXtreme Gradient Boosting (XGBoost) algorithm performed best in the internal validation process (AUC = 0.82), which was better than both the logistic regression (LR) prediction model (AUC = 0.77, p < 0.001) and the traditional scoring systems. Upon external validation, the XGBoost prediction model (AUC =0.81) also performed better than both the LR prediction model (AUC = 0.75, p = 0.03) and the traditional scoring systems. We created an online application based on the XGBoost prediction model.ConclusionsWe have developed a machine learning model that has better predictive performance than traditional LR prediction models as well as other existing risk scoring systems for postoperative ARF. This model can be utilized to provide early warnings when high-risk patients are found, enabling clinicians to take prompt measures.

Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes

Background Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. Methods RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by “limma_3.42.2” package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays. Results The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. Conclusions We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.

Development of a radiomics model to diagnose pheochromocytoma preoperatively: a multicenter study with prospective validation

Background Preoperative diagnosis of pheochromocytoma (PHEO) accurately impacts preoperative preparation and surgical outcome in PHEO patients. Highly reliable model to diagnose PHEO is lacking. We aimed to develop a magnetic resonance imaging (MRI)-based radiomic-clinical model to distinguish PHEO from adrenal lesions. Methods In total, 305 patients with 309 adrenal lesions were included and divided into different sets. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. In addition, a nomogram incorporating the obtained radiomics signature and selected clinical predictors was developed by using multivariable logistic regression analysis. The performance of the radiomic-clinical model was assessed with respect to its discrimination, calibration, and clinical usefulness. Results Seven radiomics features were selected among the 1301 features obtained as they could differentiate PHEOs from other adrenal lesions in the training (area under the curve [AUC], 0.887), internal validation (AUC, 0.880), and external validation cohorts (AUC, 0.807). Predictors contained in the individualized prediction nomogram included the radiomics signature and symptom number (symptoms include headache, palpitation, and diaphoresis). The training set yielded an AUC of 0.893 for the nomogram, which was confirmed in the internal and external validation sets with AUCs of 0.906 and 0.844, respectively. Decision curve analyses indicated the nomogram was clinically useful. In addition, 25 patients with 25 lesions were recruited for prospective validation, which yielded an AUC of 0.917 for the nomogram. Conclusion We propose a radiomic-based nomogram incorporating clinically useful signatures as an easy-to-use, predictive and individualized tool for PHEO diagnosis.

Derivation and External Validation of a Simple Prediction Rule for the Development of Respiratory Failure in Hospitalized Patients With Influenza

BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients.METHODS: a prospective cohort study was conducted during two consecutive Influenza seasons (December 2016 - March 2017 and December 2017 - April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 - May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p<0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher’s test p>0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient´s stratification during seasonal Influenza epidemics.

Algorithmic Fairness and Bias Mitigation for Clinical Machine Learning: Insights from Rapid COVID-19 Diagnosis by Adversarial Learning

Machine learning is becoming increasingly promi- nent in healthcare. Although its benefits are clear, growing attention is being given to how machine learning may exacerbate existing biases and disparities. In this study, we introduce an adversarial training framework that is capable of mitigating biases that may have been acquired through data collection or magnified during model development. For example, if one class is over-presented or errors/inconsistencies in practice are reflected in the training data, then a model can be biased by these. To evaluate our adversarial training framework, we used the statistical definition of equalized odds. We evaluated our model for the task of rapidly predicting COVID-19 for patients presenting to hospital emergency departments, and aimed to mitigate regional (hospital) and ethnic biases present. We trained our framework on a large, real-world COVID-19 dataset and demonstrated that adversarial training demonstrably improves outcome fairness (with respect to equalized odds), while still achieving clinically-effective screening performances (NPV>0.98). We compared our method to the benchmark set by related previous work, and performed prospective and external validation on four independent hospital cohorts. Our method can be generalized to any outcomes, models, and definitions of fairness.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Early Hepatocellular Carcinoma: A Study Based on SEER Database

Background: Primary liver cancer is a common malignant tumor primarily represented by hepatocellular carcinoma (HCC). The number of elderly patients with early HCC is increasing, and older age is related to a worse prognosis. However, an accurate predictive model for the prognosis of these patients is still lacking.Methods: Data of eligible elderly patients with early HCC in Surveillance, Epidemiology, and End Results database from 2010 to 2016 were downloaded. Patients from 2010 to 2015 were randomly assigned to the training cohort (n = 1093) and validation cohort (n = 461). Patients' data in 2016 (n = 431) was used for external validation. Independent prognostic factors were obtained using univariate and multivariate analyses. Based on these factors, a cancer-specific survival (CSS) nomogram was constructed. The predictive performance and clinical practicability of our nomogram were validated. According to the risk scores of our nomogram, patients were divided into low-, intermediate-, and high-risk groups. A survival analysis was performed using Kaplan–Meier curves and log-rank tests.Results: Age, race, T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent predictors for CSS and thus were included in our nomogram. In the training cohort and validation cohort, the concordance indices (C-indices) of our nomogram were 0.739 (95% CI: 0.714–0.764) and 0.756 (95% CI: 0.719–0.793), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves (AUCs) showed similar results. Calibration curves revealed high consistency between observations and predictions. In external validation cohort, C-index (0.802, 95%CI: 0.778–0.826) and calibration curves also revealed high consistency between observations and predictions. Compared with the TNM stage, nomogram-related decision curve analysis (DCA) curves indicated better clinical practicability. Kaplan–Meier curves revealed that CSS significantly differed among the three different risk groups. In addition, an online prediction tool for CSS was developed.Conclusions: A web-based prediction model for CSS of elderly patients with early HCC was constructed and validated, and it may be helpful for the prognostic evaluation, therapeutic strategy selection, and follow-up management of these patients.

Stability of CubeSat Clocks and Their Impacts on GNSS Radio Occultation

Global Navigation Satellite Systems’ radio occultation (GNSS-RO) provides the upper troposphere-lower stratosphere (UTLS) vertical atmospheric profiles that are complementing radiosonde and reanalysis data. Such data are employed in the numerical weather prediction (NWP) models used to forecast global weather as well as in climate change studies. Typically, GNSS-RO operates by remotely sensing the bending angles of an occulting GNSS signal measured by larger low Earth orbit (LEO) satellites. However, these satellites are faced with complexities in their design and costs. CubeSats, on the other hand, are emerging small and cheap satellites; the low prices of building them and the advancements in their components make them favorable for the GNSS-RO. In order to be compatible with GNSS-RO requirements, the clocks of the onboard receivers that are estimated through the precise orbit determination (POD) should have short-term stabilities. This is essential to correctly time tag the excess phase observations used in the derivation of the GNSS-RO UTLS atmospheric profiles. In this study, the stabilities of estimated clocks of a set of CubeSats launched for GNSS-RO in the Spire Global constellation are rigorously analysed and evaluated in comparison to the ultra-stable oscillators (USOs) onboard the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC-2) satellites. Methods for improving their clock stabilities are proposed and tested. The results (i) show improvement of the estimated clocks at the level of several microseconds, which increases their short-term stabilities, (ii) indicate that the quality of the frequency oscillator plays a dominant role in CubeSats’ clock instabilities, and (iii) show that CubeSats’ derived UTLS (i.e., tropopause) atmospheric profiles are comparable to those of COSMIC-2 products and in situ radiosonde observations, which provided external validation products. Different comparisons confirm that CubeSats, even those with unstable onboard clocks, provide high-quality RO profiles, comparable to those of COSMIC-2. The proposed remedies in POD and the advancements of the COTS components, such as chip-scale atomic clocks and better onboard processing units, also present a brighter future for real-time applications that require precise orbits and stable clocks.

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge

Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge—the largest histopathology competition to date, joined by 1,290 developers—to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840–0.884) and 0.868 (95% CI, 0.835–0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.