Previously published photoplethysmography-(PPG) based non-invasive blood glucose (NIBG) measurements have not yet been validated over 500 subjects. As illustrated in this work, we increased the number subjects recruited to 2538 and found that the prediction accuracy (the ratio in zone A of Clarke’s error grid) reduced to undesirable 60.6%. We suspect the low prediction accuracy induced by larger sample size might arise from the physiological diversity of subjects, and one possibility is that the diversity might originate from medication. Therefore, we split the subjects into two cohorts for deep learning: with and without medication (1682 and 856 recruited subjects, respectively). In comparison, the cohort training for subjects without any medication had approximately 30% higher prediction accuracy over the cohort training for those with medication. Furthermore, by adding quarterly (every 3 months) measured glycohemoglobin (HbA1c), we were able to significantly boost the prediction accuracy by approximately 10%. For subjects without medication, the best performing model with quarterly measured HbA1c achieved 94.3% prediction accuracy, RMSE of 12.4 mg/dL, MAE of 8.9 mg/dL, and MAPE of 0.08, which demonstrates a very promising solution for NIBG prediction via deep learning. Regarding subjects with medication, a personalized model could be a viable means of further investigation.
Previous non-invasive Diabetes Mellitus (DM) prediction methods for rapid screening suffered from the trade-off between speed and accuracy. The accurate results of questionnaires rely on long and detailed questions thus sacrifice speed, meanwhile, photoplethysmography (PPG) offers convenient and fast testing but lacking accuracy. In this work, we developed a 5-grade model to accurately screen out non-DM subjects (low prediction grades) via one-minute PPG measurement. This efficient and effective rapid screening will practically reduce the loading for further invasive verification on the remaining DM-grade subjects. A total of 2538 subjects are recruited (DM: 1310, non-DM: 1228) with two 1-minute PPG samples taken from each subject. The model includes 8 features: 3 autonomic-and 3 vascular-related PPG features, heart rate, and waist circumference. All 8 features monotonically alter with increased DM prediction grade. The model provides users 5 DM risk grades. While defined grade 1 and grade 2 as non-DM grades, the prediction result shows a low false-negative rate of 13%. If only considering grade 1 as non-DM, the false-negative rate will be significantly reduced to 1.3%. Thus subjects predicted as grades 1 and 2 are substantially away from DM. The remaining subjects with higher DM risk grades such as grades 3, 4, and 5 (or unlikely grade 2) are recommended to take clinical-standard invasive DM test for corresponding therapeutic treatment. A table for assessing the risk index for each feature is also compiled. We have experimentally demonstrated a 1-minute pulsation measurement with PPG-based device (SpO 2 oximeter, smartphone, or wearable device) can be an efficient/effective DM rapid screening technique to filter out non-DM subjects. The resulted high-risk feature indexes also pose as warning signs of the degradation of either autonomic or vascular functions for personal healthcare management. The fast and convenient execution and useful results suggest that our approach is very simple and informative for quick DM risk assessment.
Compared to other techniques, RNA sequencing (RNA-Seq) has the advantage of having details of the expression abundance of all transcripts in a single run. In this study, we used RNA-Seq to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. Hepatocytes, including mature hepatocytes and small hepatocytes, were analyzed in vitro using RNA-Seq and quantitative polymerase chain reaction (qPCR). The results demonstrated that the gene expression profiles measured by RNA-Seq showed a similar trend to the expression profiles measured by qPCR, and can be used to infer the success of in vitro hepatocyte cultures. The results of the differential analysis, which compared mature hepatocytes against small hepatocytes, revealed 836 downregulated and 137 upregulated genes. In addition, the success of the hepatocyte cultures could be explained by the gene list screened from the adopted gene enrichment test. In summary, we demonstrated that RNA-Seq could become an effective method for monitoring the whole transcriptome of hepatocyte cultures and provide a more comprehensive list of factors related to the differentiation of small hepatocytes into mature hepatocytes. This monitoring system not only shows high potential in medical applications but may also be a novel method for the clinical diagnosis of liver-related diseases.
Personalized modeling has long been anticipated to approach precise noninvasive blood glucose measurements, but challenged by limited data for training personal model and its unavoidable outlier predictions. To overcome these long-standing problems, we largely enhanced the training efficiency with the limited personal data by an innovative Deduction Learning (DL), instead of the conventional Induction Learning (IL). The domain theory of our deductive method, DL, made use of accumulated comparison of paired inputs leading to corrections to preceded measured blood glucose to construct our deep neural network architecture. DL method involves the use of paired adjacent rounds of finger pulsation Photoplethysmography signal recordings as the input to a convolutional-neural-network (CNN) based deep learning model. Our study reveals that CNN filters of DL model generated extra and non-uniform feature patterns than that of IL models, which suggests DL is superior to IL in terms of learning efficiency under limited training data. Among 30 diabetic patients as our recruited volunteers, DL model achieved 80% of test prediction in zone A of Clarke Error Grid (CEG) for model training with 12 rounds of data, which was 20% improvement over IL method. Furthermore, we developed an automatic screening algorithm to delete low confidence outlier predictions. With only a dozen rounds of training data, DL with automatic screening achieved a correlation coefficient ($${R}_{P}$$ R P ) of 0.81, an accuracy score ($${R}_{A}$$ R A ) of 93.5, a root mean squared error of 13.93 mg/dl, a mean absolute error of 12.07 mg/dl, and 100% predictions in zone A of CEG. The nonparametric Wilcoxon paired test on $${R}_{A}$$ R A for DL versus IL revealed near significant difference with p-value 0.06. These significant improvements indicate that a very simple and precise noninvasive measurement of blood glucose concentration is achievable.
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