Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations. To investigate this question, we applied single-cell DNA and RNA sequencing in addition to bulk exome sequencing to profile longitudinal samples from 20 TNBC patients during neoadjuvant chemotherapy (NAC). Deep-exome sequencing identified 10 patients in which NAC led to clonal extinction and 10 patients in which clones persisted after treatment. In 8 patients, we performed a more detailed study using single-cell DNA sequencing to analyze 900 cells and single-cell RNA sequencing to analyze 6,862 cells. Our data showed that resistant genotypes were pre-existing and adaptively selected by NAC, while transcriptional profiles were acquired by reprogramming in response to chemotherapy in TNBC patients.

The accurate real-time estimation of PIC will benefit the AP systems by preventing overdelivery of insulin when significant insulin is present in the bloodstream.

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Algorithms that can determine the type of physical activity (PA) and quantify the intensity can allow precision medicine approaches, such as automated insulin delivery systems that modulate insulin administration in response to PA. In this work, data from a multi-sensor wristband is used to design classifiers to distinguish among five different physical states (PS) (resting, activities of daily living, running, biking, and resistance training), and to develop models to estimate the energy expenditure (EE) of the PA for diabetes therapy. The data collected are filtered, features are extracted from the reconciled signals, and the extracted features are used by machine learning algorithms, including deep-learning techniques, to obtain accurate PS classification and EE estimation. The various machine learning techniques have different success rates ranging from 75.7% to 94.8% in classifying the five different PS. The deep neural network model with long short-term memory has 94.8% classification accuracy. We achieved 0.5 MET (Metabolic Equivalent of Task) root-mean-square error for EE estimation accuracy, relative to indirect calorimetry with randomly selected testing data (10% of collected data). We also demonstrate a 5% improvement in PS classification accuracy and a 0.34 MET decrease in the mean absolute error when using multi-sensor approach relative to using only accelerometer data.