12 research outputs found

    Applying interpretable machine learning workflow to evaluate exposure–response relationships for large‐molecule oncology drugs

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    Abstract The application of logistic regression (LR) and Cox Proportional Hazard (CoxPH) models are well‐established for evaluating exposure–response (E–R) relationship in large molecule oncology drugs. However, applying machine learning (ML) models on evaluating E–R relationships has not been widely explored. We developed a workflow to train regularized LR/CoxPH and tree‐based XGboost (XGB) models, and derive the odds ratios for best overall response and hazard ratios for overall survival, across exposure quantiles to evaluate the E–R relationship using clinical trial datasets. The E–R conclusions between LR/CoxPH and XGB models are overall consistent, and largely aligned with historical pharmacometric analyses findings. Overall, applying this interpretable ML workflow provides a promising alternative method to assess E–R relationships for impacting key dosing decisions in drug development

    Morphological changes of gonad and gene expression patterns during desexualization in Dugesia japonica (Platyhelminthes: Dugesiidae)

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    ABSTRACT Planarians, the representatives of an ancient bilaterian group with complex reproductive system and high regenerative capabilities, are model system suitable for studying the basic molecular requirements for the development of the reproductive system. To further explore the morphological changes of the gonads during desexualization and the molecular events of the genes controlling the reproductive system development in planarians, we have investigated the histological changes of ovary and testis by paraffin section and the expression patterns of reproductive-related genes by the quantitative real-time PCR in Dugesia japonica Ichikawa & Kawakatsu, 1964, upon starvation. The four genes, Djprps, DjvlgA, DjvlgB and Djnos, have been selected. The research results show that the degradation of ovary changes from outside layer to inside, and the testis changes are opposite; the reproductive capacity of the planarians starts to be damaged from the 17th to 25th days and to disappear completely from the 26th to 37th days during starvation. The expression patterns of the four genes exhibit the obvious dynamic variations during their desexualization, which indicates that these genes might be involved in gonad development

    Inter-Patient Congestive Heart Failure Detection Using ECG-Convolution-Vision Transformer Network

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    An attack of congestive heart failure (CHF) can cause symptoms such as difficulty breathing, dizziness, or fatigue, which can be life-threatening in severe cases. An electrocardiogram (ECG) is a simple and economical method for diagnosing CHF. Due to the inherent complexity of ECGs and the subtle differences in the ECG waveform, misdiagnosis happens often. At present, the research on automatic CHF detection methods based on machine learning has become a research hotspot. However, the existing research focuses on an intra-patient experimental scheme and lacks the performance evaluation of working under noise, which cannot meet the application requirements. To solve the above issues, we propose a novel method to identify CHF using the ECG-Convolution-Vision Transformer Network (ECVT-Net). The algorithm combines the characteristics of a Convolutional Neural Network (CNN) and a Vision Transformer, which can automatically extract high-dimensional abstract features of ECGs with simple pre-processing. In this study, the model reached an accuracy of 98.88% for the inter-patient scheme. Furthermore, we added different degrees of noise to the original ECGs to verify the model’s noise robustness. The model’s performance in the above experiments proved that it could effectively identify CHF ECGs and can work under certain noise
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