Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.
Background
Extensive clinical evidence suggests that a preventive screening of coronary heart disease (CHD) at an earlier stage can greatly reduce the mortality rate. We use 64 two-dimensional speckle tracking echocardiography (2D-STE) features and seven clinical features to predict whether one has CHD.
Methods
We develop a machine learning approach that integrates a number of popular classification methods together by model stacking, and generalize the traditional stacking method to a two-step stacking method to improve the diagnostic performance.
Results
By borrowing strengths from multiple classification models through the proposed method, we improve the CHD classification accuracy from around 70–87.7% on the testing set. The sensitivity of the proposed method is 0.903 and the specificity is 0.843, with an AUC of 0.904, which is significantly higher than those of the individual classification models.
Conclusion
Our work lays a foundation for the deployment of speckle tracking echocardiography-based screening tools for coronary heart disease.
Smoothing splines have been used pervasively in nonparametric regressions. However, the computational burden of smoothing splines is significant when the sample size n is large. When the number of predictors d ≥ 2, the computational cost for smoothing splines is at the order of O(n 3 ) using the standard approach. Many methods have been developed to approximate smoothing spline estimators by using q basis functions instead of n ones, resulting in a computational cost of the order O(nq 2 ). These methods are called the basis selection methods.Despite algorithmic benefits, most of the basis selection methods require the assumption that the sample is uniformly-distributed on a hyper-cube. These methods may have deteriorating performance when such an assumption is not met. To overcome the obstacle, we develop an efficient algorithm that is adaptive to the unknown probability density function of the predictors.Theoretically, we show the proposed estimator has the same convergence rate as the full-basis estimator when q is roughly at the order of O[n 2d/{(pr+1)(d+2)} ], where p ∈ [1, 2] and r ≈ 4 are some constants depend on the type of the spline. Numerical studies on various synthetic datasets demonstrate the superior performance of the proposed estimator in comparison with mainstream competitors.
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