Combined measurement of serum zinc with PSA ameliorates prostate cancer screening efficiency via support vector machine algorithms.

Background: Early screening of prostate cancer (PCa) is pivotal but challenging in the clinical scenario due to the phenomena of false positivity or false negativity of some serological evaluations, e.g. PSA testing. Decline of serum Zn2+ levels in PCa patients reportedly plays a crucial role in early screening of PCa. Accordingly, we combined 4 indices comprising the serum levels of total PSA (tPSA), free PSA (fPSA), Zn2+ and demographic information (especially age) in order to ameliorate the efficacies of PCa screening with support vector machine (SVM) algorithms. Methods: A total of 858 male patients with prostate disorders and 345 healthy male controls were enrolled. Patients' data included 4 variables and serum Zn2+ was quantified via a self-invented Zn2+ responsive AIE-based fluorescent probe as previously published. tPSA and fPSA were routinely determined by a chemiluminescent method. Mathematical simulations were conducted to establish a SVM model for the combined diagnostics with the four variables. Moreover, ROC and its characteristic AUC were also employed to evaluate the classification efficacy of the model. Sigmoid function was utilized to estimate corresponding probabilities of classifying the clinical subjects as per 5 grades, which were incorporated into our established prostate index (PI) stratification system. Results: In SVM model, the mean AUC of the ROC with the quartet of variables was approximately 84% for PCa diagnosis, whereas the mean AUC of the ROCs with tPSA, fPSA, [Zn2+] or age alone was 64%, 62%, 55% and 59%, respectively. We further established an integrated prostate index (PI) stratification system with 5 grades and a software package to support clinicians in predicting PCa, with the accuracy of our risk stratification system being 83.3%, 91.6% and 83.3% in predicting normal, benign and PCa cases in corresponding groups. Follow-up findings especially MRI results and PI-RADS scores supported the reliability of this stratification platform as well. Conclusion: Findings from our present study demonstrated that index combination via SVM algorithms may well facilitate clinicians in early differential screening of PCa. Meanwhile, our established PI stratification system based on SVM model and Sigmoid function provided substantial accuracy in preclinical risk prediction of developing prostate cancer.

ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3-mediated induction of p21.

Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS.

SEA-Net: Structure-Enhanced Attention Network for Limited-Angle CBCT Reconstruction of Clinical Projection Data.

This work aims to improve limited-angle (LA) cone beam computed tomography (CBCT) by developing deep learning (DL) methods for real clinical CBCT projection data, which is the first feasibility study of clinical-projection-data-based LA-CBCT, to the best of our knowledge. In radiation therapy (RT), CBCT is routinely used as the on-board imaging modality for patient setup. Compared to diagnostic CT, CBCT has a long acquisition time, e.g., 60 seconds for a full 360° rotation, which is subject to the motion artifact. Therefore, the LA-CBCT, if achievable, is of the great interest for the purpose of RT, for its proportionally reduced scanning time in addition to the radiation dose. However, LA-CBCT suffers from severe wedge artifacts and image distortions. Targeting at real clinical projection data, we have explored various DL methods such as image/data/hybrid-domain methods and finally developed a so-called Structure-Enhanced Attention Network (SEA-Net) method that has the best image quality from clinical projection data among the DL methods we have implemented. Specifically, the proposed SEA-Net employs a specialized structure enhancement sub-network to promote texture preservation. Based on the observation that the distribution of wedge artifacts in reconstruction images is non-uniform, the spatial attention module is utilized to emphasize the relevant regions while ignores the irrelevant ones, which leads to more accurate texture restoration.

AirNet: Fused analytical and iterative reconstruction with deep neural network regularization for sparse-data CT.

PURPOSE: Sparse-data computed tomography (CT) frequently occurs, such as breast tomosynthesis, C-arm CT, on-board four-dimensional cone-beam CT (4D CBCT), and industrial CT. However, sparse-data image reconstruction remains challenging due to highly undersampled data. This work develops a data-driven image reconstruction method for sparse-data CT using deep neural networks (DNN). METHODS: The new method so-called AirNet is designed to incorporate the benefits from analytical reconstruction method (AR), iterative reconstruction method (IR), and DNN. It is built upon fused analytical and iterative reconstruction (AIR) that synergizes AR and IR via the optimization framework of modified proximal forward-backward splitting (PFBS). By unrolling PFBS into IR updates of CT data fidelity and DNN regularization with residual learning, AirNet utilizes AR such as FBP during the data fidelity, introduces dense connectivity into DNN regularization, and learns PFBS coefficients and DNN parameters that minimize the loss function during the training stage; and then AirNet with trained parameters can be used for end-to-end image reconstruction. RESULTS: A CT atlas of 100 prostate scans was used to validate the AirNet in comparison with state-of-art DNN-based postprocessing and image reconstruction methods. The validation loss in AirNet had the fastest decreasing rate, owing to inherited fast convergence from AIR. AirNet was robust to noise in projection data and content differences between the training set and the images to be reconstructed. The impact of image quality on radiotherapy treatment planning was evaluated for both photon and proton therapy, and AirNet achieved the best treatment plan quality, especially for proton therapy. For example, with limited-angle data, the maximal target dose for AirNet was 109.5% in comparison with the ground truth 109.1%, while it was significantly elevated to 115.1% and 128.1% for FBPConvNet and LEARN, respectively. CONCLUSIONS: A new image reconstruction AirNet is developed for sparse-data CT image reconstruction. AirNet achieved the best image reconstruction quality both visually and quantitatively among all methods under comparison for all sparse-data scenarios (sparse-view and limited-angle), and provided the best photon and proton treatment plan quality based on sparse-data CT.