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Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation of established cellular effectors overcomes impediments to enhance reparative activity. Such ‘next generation’ implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, previously reported by our group, prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Herein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. scRNA-Seq profiling reveals CardioCluster expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines, while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster intramyocardial delivery improves cell retention and capillary density with preservation of cardiomyocyte size and long-term cardiac function in a murine infarction model followed 20 weeks. CardioCluster utilization in this preclinical setting establish fundamental insights, laying the framework for optimization in cell-based therapeutics intended to mitigate cardiomyopathic damage., Despite recent progress to advance cardiac cell-based therapy for patients, heart failure mortality rivals most cancers. Here, the authors describe an approach to control and pattern 3 distinct human cardiac cell populations to promote superior repair and regeneration after myocardial infarction.

Labeling training data is increasingly the largest bottleneck in deploying machine learning systems. We present Snorkel, a first-of-its-kind system that enables users to train state-of-the-art models without hand labeling any training data. Instead, users write labeling functions that express arbitrary heuristics, which can have unknown accuracies and correlations. Snorkel denoises their outputs without access to ground truth by incorporating the first end-to-end implementation of our recently proposed machine learning paradigm, data programming. We present a flexible interface layer for writing labeling functions based on our experience over the past year collaborating with companies, agencies, and research laboratories. In a user study, subject matter experts build models \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.8\times $$\end{document}2.8× faster and increase predictive performance an average \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$45.5\%$$\end{document}45.5% versus seven hours of hand labeling. We study the modeling trade-offs in this new setting and propose an optimizer for automating trade-off decisions that gives up to \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.8\times $$\end{document}1.8× speedup per pipeline execution. In two collaborations, with the US Department of Veterans Affairs and the US Food and Drug Administration, and on four open-source text and image data sets representative of other deployments, Snorkel provides \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$132\%$$\end{document}132% average improvements to predictive performance over prior heuristic approaches and comes within an average \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.60\%$$\end{document}3.60% of the predictive performance of large hand-curated training sets.

Populating large-scale structured databases from unstructured sources is a critical and challenging task in data analytics. As automated feature engineering methods grow increasingly prevalent, constructing sufficiently large labeled training sets has become the primary hurdle in building machine learning information extraction systems. In light of this, we have taken a new approach called data programming [7]. Rather than hand-labeling data, in the data programming paradigm, users generate large amounts of noisy training labels by programmatically encoding domain heuristics as simple rules. Using this approach over more traditional distant supervision methods and fully supervised approaches using labeled data, we have been able to construct knowledge base systems more rapidly and with higher quality. Since the ability to quickly prototype, evaluate, and debug these rules is a key component of this paradigm, we introduce DDLite, an interactive development framework for data programming. This paper reports feedback collected from DDLite users across a diverse set of entity extraction tasks. We share observations from several DDLite hackathons in which 10 biomedical researchers prototyped information extraction pipelines for chemicals, diseases, and anatomical named entities. Initial results were promising, with the disease tagging team obtaining an F1 score within 10 points of the state-of-the-art in only a single day-long hackathon's work. Our key insights concern the challenges of writing diverse rule sets for generating labels, and exploring training data. These findings motivate several areas of active data programming research.

Objectives: Advances in multiparametric magnetic resonance imaging (mpMRI) and ultrasound/MRI fusion imaging offer a powerful alternative to the typical undirected approach to diagnosing prostate cancer. However, these methods require the time and expertise needed to interpret mpMRI image scenes. In this paper, a machine learning framework for automatically detecting and localizing cancerous lesions within the prostate is developed and evaluated. Methods: Two studies were performed to gather MRI and pathology data. The 12 patients in the first study underwent an MRI session to obtain structural, diffusion-weighted, and dynamic contrast enhanced image vol- umes of the prostate, and regions suspected of being cancerous from the MRI data were manually contoured by radiologists. Whole-mount slices of the prostate were obtained for the patients in the second study, in addition to structural and diffusion-weighted MRI data, for pathology verification. A 3-D feature set for voxel-wise appear- ance description combining intensity data, textural operators, and zonal approximations was generated. Voxels in a test set were classified as normal or cancer using a decision forest-based model initialized using Gaussian discriminant analysis. A leave-one-patient-out cross-validation scheme was used to assess the predictions against the expert manual segmentations confirmed as cancer by biopsy. Results: We achieved an area under the average receiver-operator characteristic curve of 0.923 for the first study, and visual assessment of the probability maps showed 21 out of 22 tumors were identified while a high level of specificity was maintained. In addition to evaluating the model against related approaches, the effects of the individual MRI parameter types were explored, and pathological verification using whole-mount slices from the second study was performed. Conclusions: The results of this paper show that the combination of mpMRI and machine learning is a powerful tool for quantitatively diagnosing prostate cancer.