Background End stage renal disease (ESRD) describes the most severe stage of chronic kidney disease (CKD), when patients need dialysis or renal transplant. There is often a delay in recognizing, diagnosing, and treating the various etiologies of CKD. The objective of the present study was to employ machine learning algorithms to develop a prediction model for progression to ESRD based on a large-scale multidimensional database. Methods This study analyzed 10,000,000 medical insurance claims from 550,000 patient records using a commercial health insurance database. Inclusion criteria were patients over the age of 18 diagnosed with CKD Stages 1–4. We compiled 240 predictor candidates, divided into six feature groups: demographics, chronic conditions, diagnosis and procedure features, medication features, medical costs, and episode counts. We used a feature embedding method based on implementation of the Word2Vec algorithm to further capture temporal information for the three main components of the data: diagnosis, procedures, and medications. For the analysis, we used the gradient boosting tree algorithm (XGBoost implementation). Results The C-statistic for the model was 0.93 [(0.916–0.943) 95% confidence interval], with a sensitivity of 0.715 and specificity of 0.958. Positive Predictive Value (PPV) was 0.517, and Negative Predictive Value (NPV) was 0.981. For the top 1 percentile of patients identified by our model, the PPV was 1.0. In addition, for the top 5 percentile of patients identified by our model, the PPV was 0.71. All the results above were tested on the test data only, and the threshold used to obtain these results was 0.1. Notable features contributing to the model were chronic heart and ischemic heart disease as a comorbidity, patient age, and number of hypertensive crisis events. Conclusions When a patient is approaching the threshold of ESRD risk, a warning message can be sent electronically to the physician, who will initiate a referral for a nephrology consultation to ensure an investigation to hasten the establishment of a diagnosis and initiate management and therapy when appropriate.
The amygdala is one of the most widely studied regions in behavioral neuroscience. A plethora of classical, and new paradigms have dissected its precise involvement in emotional and social sensing, learning, and memory. Several important insights resulted from the use of genetic markers - yet, in the age of single cell transcriptomics, the amygdala remains molecularly underdescribed. Here, we present a molecular cell type taxonomy of the full mouse amygdala in fear learning and consolidation. We performed single-cell RNA-seq on naïve and fear conditioned mice, inferred the 130 neuronal cell types distributions in silico using orthogonal spatial transcriptomic datasets, and describe the cell types' transcriptional responses to learning and memory consolidation. Only a fraction of cells, within a subset of all neuronal types, were transcriptionally responsive to fear learning, memory and retrieval. These activated engram cells upregulated activity-response genes, and processes of synaptic signaling, plasticity, development and neurite outgrowth. Our transcriptome-wide data confirm known actors, and describe several new candidate genes. The atlas may help pinpoint the amygdala's circuits in performing emotional sensing and integration, and provide new insights to the global cellular processes involved.
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