Identifying microRNAs associated with tumor immunotherapy response using an interpretable machine learning model.

Predicting clinical responses to tumor immunotherapy is essential to reduce side effects and the potential for sustained clinical responses. Nevertheless, preselecting patients who are likely to respond to such treatments remains highly challenging. Here, we explored the potential of microRNAs (miRNAs) as predictors of immune checkpoint blockade responses using a machine learning approach. First, we constructed random forest models to predict the response to tumor ICB therapy using miRNA expression profiles across 19 cancer types. The contribution of individual miRNAs to each prediction process was determined by employing SHapley Additive exPlanations (SHAP) for model interpretation. Remarkably, the predictive performance achieved by using a small number of miRNAs with high feature importance was similar to that achieved by using the entire miRNA set. Additionally, the genes targeted by these miRNAs were closely associated with tumor- and immune-related pathways. In conclusion, this study demonstrates the potential of miRNA expression data for assessing tumor immunotherapy responses. Furthermore, we confirmed the potential of informative miRNAs as biomarkers for the prediction of immunotherapy response, which will advance our understanding of tumor immunotherapy mechanisms.

Chromophoric cerium oxide nanoparticle-loaded sucking disk-type strip sensor for optical measurement of glucose in tear fluid.

BACKGROUND: Noninvasive monitoring of tear glucose levels can be convenient for patients to manage their diabetes mellitus. However, there are issues with monitoring tear glucose levels, such as the invasiveness of some methods, the miniaturization, inaccuracy, or the high cost of wearable devices. To overcome the issues, we newly designed a sucking disk-type (SD) strip biosensor that can quickly suck tear fluid and contains cerium oxide nanoparticle (CNP) that causes a unique color change according to the glucose level of the tear without complicated electronic components. METHODS: The SD strip biosensor composed of three distinct parts (tip, channel, and reaction chamber) was designed to contain the sensing paper, onto which tear fluid can be collected and delivered. The sensing paper treated with CNP/APTS (aminopropyltriethoxysilane) /GOx (glucose oxidase) was characterized. Then we carried out the reliability of the SD strip biosensor in the diabetic rabbit animals. We quantitatively analyzed the color values of the SD strip biosensor through the colorimetric analysis algorithm. RESULTS: We contacted the inferior palpebral conjunctiva (IPC) of a diabetic rabbit eye using an SD strip biosensor to collect tears without eye irritation and successfully verified the performance and quantitative efficacy of the sensor. An image processing algorithm that can optimize measurement accuracy is developed for accurate color change measurement of SD strip biosensors. The validation tests show a good correlation between glucose concentrations measured in the tear and blood. CONCLUSION: Our findings demonstrate that the CNP-embedded SD strip biosensor and the associated image processing can simply monitor tear glucose to manage diabetes mellitus.

Assessment of MicroRNAs Associated with Tumor Purity by Random Forest Regression.

Tumor purity refers to the proportion of tumor cells in tumor tissue samples. This value plays an important role in understanding the mechanisms of the tumor microenvironment. Although various attempts have been made to predict tumor purity, attempts to predict tumor purity using miRNAs are still lacking. We predicted tumor purity using miRNA expression data for 16 TCGA tumor types using random forest regression. In addition, we identified miRNAs with high feature-importance scores and examined the extent of the change in predictive performance using informative miRNAs. The predictive performance obtained using only 10 miRNAs with high feature importance was close to the result obtained using all miRNAs. Furthermore, we also found genes targeted by miRNAs and confirmed that these genes were mainly related to immune and cancer pathways. Therefore, we found that the miRNA expression data could predict tumor purity well, and the results suggested the possibility that 10 miRNAs with high feature importance could be used as potential markers to predict tumor purity and to help improve our understanding of the tumor microenvironment.

Designing Minimally Invasive Preocular Contact Tips for Potential Application in Tear Collection.

PURPOSE: Basal tear fluid has drawn great attention as a medium for many disease markers and, hence, for its potential to be used in self-diagnosis. However, collection of basal tear fluid is difficult because a conventional tear collector, such as a glass capillary tube, may inflict irritation or damage on the sensitive ocular surface. Therefore, we sought to design a tip for contact with the preocular surface [a preocular contact tip (PCT)] that minimizes damage to the ocular surface. METHODS: We designed the shape of the tip to have rounded boundaries and no sharp edges. We then tested different tip areas, each of which was contacted with the inferior palpebral conjunctiva of rabbit eyes at varying depths to demonstrate their feasibility in vivo. The area of damaged tissue and the time required for tissue recovery were monitored according to the pressure applied through the tips. RESULTS: Our findings revealed that a contact area of the PCT greater than 2.36 mm caused relatively little damage to the inferior palpebral conjunctival tissue, which could recover within 4 hours after contact at all pressing depths. In contrast, a glass capillary tube caused relatively severe damage, which did not recover for more than 8 hours. The PCT (3.14 mm) was embedded with a microchannel as a prototype tear collector, which could collect 0.3 µL of tears with minimal tissue damage. CONCLUSIONS: The PCT proposed in this study can be a promising tool for minimally invasive collection of basal tears from the inferior palpebral conjunctiva.