Tissue-Engineered Constructs of Human Oral Mucosa Examined by Raman Spectroscopy

A noninvasive quality monitoring of tissue-engineered constructs is a required component of any successful tissue-engineering technique. During a 2-week production period, ex vivo produced oral mucosa-equivalent constructs (EVPOMEs) may encounter adverse culturing conditions that might compromise their quality and render them ineffective. We demonstrate the application of near-infrared Raman spectroscopy to in vitro monitoring of EVPOMEs during their manufacturing process, with the ultimate goal of applying this technology in situ to monitor the grafted EVPOMEs. We identify Raman spectroscopic failure indicators for less-than optimal EVPOMEs that are stressed by higher temperature and exposure to higher than normal concentration of calcium ions. Raman spectra of EVPOMEs exposed to thermal and calcium stress showed correlation of the band height ratio of CH2 deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. We compared these results to histology and glucose consumption measurements, demonstrating that Raman spectroscopy is more sensitive and specific to changes in proteins' secondary structure not visible by HandE histology. We also exposed the EVPOMEs to rapamycin, a cell growth inhibitor and cell proliferation capacity preserver, and distinguished between EVPOMEs pretreated with 2?nM rapamycin and controls, using the ratio of the Amide III envelope to the phenylalanine band as an indicator.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140240/1/ten.tec.2012.0287.pd

Predicting Changes in Depression Severity Using the PSYCHE-D (Prediction of Severity Change-Depression) Model Involving Person-Generated Health Data: Longitudinal Case-Control Observational Study

BackgroundIn 2017, an estimated 17.3 million adults in the United States experienced at least one major depressive episode, with 35% of them not receiving any treatment. Underdiagnosis of depression has been attributed to many reasons, including stigma surrounding mental health, limited access to medical care, and barriers due to cost. ObjectiveThis study aimed to determine if low-burden personal health solutions, leveraging person-generated health data (PGHD), could represent a possible way to increase engagement and improve outcomes. MethodsHere, we present the development of PSYCHE-D (Prediction of Severity Change-Depression), a predictive model developed using PGHD from more than 4000 individuals, which forecasts the long-term increase in depression severity. PSYCHE-D uses a 2-phase approach. The first phase supplements self-reports with intermediate generated labels, and the second phase predicts changing status over a 3-month period, up to 2 months in advance. The 2 phases are implemented as a single pipeline in order to eliminate data leakage and ensure results are generalizable. ResultsPSYCHE-D is composed of 2 Light Gradient Boosting Machine (LightGBM) algorithm–based classifiers that use a range of PGHD input features, including objective activity and sleep, self-reported changes in lifestyle and medication, and generated intermediate observations of depression status. The approach generalizes to previously unseen participants to detect an increase in depression severity over a 3-month interval, with a sensitivity of 55.4% and a specificity of 65.3%, nearly tripling sensitivity while maintaining specificity when compared with a random model. ConclusionsThese results demonstrate that low-burden PGHD can be the basis of accurate and timely warnings that an individual’s mental health may be deteriorating. We hope this work will serve as a basis for improved engagement and treatment of individuals experiencing depression

Tissue-Engineered Constructs of Human Oral Mucosa Examined by Raman Spectroscopy

A noninvasive quality monitoring of tissue-engineered constructs is a required component of any successful tissue-engineering technique. During a 2-week production period, ex vivo produced oral mucosa-equivalent constructs (EVPOMEs) may encounter adverse culturing conditions that might compromise their quality and render them ineffective. We demonstrate the application of near-infrared Raman spectroscopy to in vitro monitoring of EVPOMEs during their manufacturing process, with the ultimate goal of applying this technology in situ to monitor the grafted EVPOMEs. We identify Raman spectroscopic failure indicators for less-than optimal EVPOMEs that are stressed by higher temperature and exposure to higher than normal concentration of calcium ions. Raman spectra of EVPOMEs exposed to thermal and calcium stress showed correlation of the band height ratio of CH(2) deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. We compared these results to histology and glucose consumption measurements, demonstrating that Raman spectroscopy is more sensitive and specific to changes in proteins' secondary structure not visible by H&E histology. We also exposed the EVPOMEs to rapamycin, a cell growth inhibitor and cell proliferation capacity preserver, and distinguished between EVPOMEs pretreated with 2 nM rapamycin and controls, using the ratio of the Amide III envelope to the phenylalanine band as an indicator