Sarwat, S. | bioRxiv Science

bioRxiv2020

Evaluation of optically tailored fluorescent silicon quantum dots for bioimaging of the tear film

This experimental study aimed to investigate the feasibility of using silicon quantum dots doped with transition metals: scandium, copper and zinc as contrast agents for eventual application for the study of the tear film in eyes. Si-QDs were synthesized and characterized by transmission electron microscopy, photoluminescence, absorbance and transient absorption measurements. The fluorescence of Si-QDs was investigated when combined with TheraTears(R) (a balanced electrolyte formula for dry eye therapy). An optical imaging system composed of a modified slit lamp biomicroscope combined with a high-resolution Zyla sCMOS camera, SOLIS software, custom-made optical mounts and emission filters (460 nm, 510 nm and 530 nm) were used for in vitro imaging of Si-QDs with TheraTears(R). The average size of Si-QDs was 2.65 nm. In vitro imaging of Sc-Si-QDs and Cu-Si-QDs indicated their stable and bright fluorescence with TheraTears(R). Sc-Si-QDs were significantly brighter compared to Cu-Si-QDs and Zn-Si-QDs, and the Zn-Si-QDs showed a tendency to clump in TheraTears(R). The fluorescence of the Si-QDs was detected down to a concentration of 0.01 {micro}g/mL within a total volume of 5 {micro}L. Cu-Si-QDs and Sc-Si-QDs showed brighter fluorescence than Zn-Si-QDs. However, Zn-Si-QDs and to a lesser extent, Cu-Si-QDs showed some aggregation at specific concentrations. Sc-Si-QDs are proposed as a better option for further development as an in vivo bioimaging agent to study the tear film dynamics.

biochemistry↗

bioRxiv2019

SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

ObjectivesWe extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy.\n\nMethodsWe propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain.\n\nResultsThrough simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 52.4 weeks compared to 94.4 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 51-61 weeks versus 59-77 weeks in those receiving non-d4T-based regimens.\n\nDiscussionPS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

bioinformatics↗