Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the ...biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
•The progressive face failure of a shield tunnel in sand is analyzed.•The coupled FDM-DEM is adopted.•The effect of particle shape on the failure process is investigated.•Results of soil movement, ...surface movement and supporting force are presented.•The force chains and distribution of microscopic contacts of particles are analyzed.
The face failure of tunnels has been extensively studied. However, the effect of particle shape on the failure process still remains unclear. In this paper, the progressive face failure of a shield tunnel in sand is analyzed with coupled discrete element method (DEM) and the finite difference method (FDM) in three-dimension. Soils at the tunnel face, where large deformation occurs and continuum mechanics description does not apply, are modeled with DEM. And the FDM is used for the rest areas where deformation and displacement are relatively small. In order to obtain appropriate parameters for soils as reference, a series of triaxial tests on both loose and dense soils are conducted. The face failure is generated by moving the tunnel forward and backward, which, respectively, simulates the collapse failure corresponding to the tunneling speed higher than soil excavating speed and the blow-out failure corresponding to the converse case. In particular, the effect of particle shape on the failure process is investigated in detail by adopting tetrahedral particles, elongated particles and spherical particles with rolling resistance coefficient of 0.0, 0.1, 0.2 and 0.4. The soil movement, ground surface movement, supporting force of the tunnel face, and the distribution of microscopic contacts are analyzed during the progressive failure of the tunnel face, which demonstrate a significant effect of particle shape.
Purpose
This study aimed to develop and validate a radiomics model based on whole‐brain white matter and clinical features to predict the progression of Parkinson disease (PD).
Methods
PD patient ...data from the Parkinson's Progress Markers Initiative (PPMI) database was evaluated. Seventy‐two PD patients with disease progression, as measured by the Hoehn‐Yahr Scale (HYS) (stage 1‐5), and 72 PD patients with stable PD were matched by sex, age, and category of HYS and included in the current study. Each individual’s T1‐weighted MRI scans at the baseline timepoint were segmented to isolate whole‐brain white matter for radiomics feature extraction. The total dataset was divided into a training and test set according to subject serial number. The size of the training dataset was reduced using the maximum relevance minimum redundancy (mRMR) algorithm to construct a radiomics signature using machine learning. Finally, a joint model was constructed by incorporating the radiomics signature and clinical progression scores. The test data were then used to validate the prediction models, which were evaluated based on discrimination, calibration, and clinical utility.
Results
Based on the overall data, the areas under curve (AUCs) of the joint model, signature and Unified Parkinson Disease Rating Scale III PD rating score were 0.836, 0.795, and 0.550, respectively. Furthermore, the sensitivities were 0.805, 0.875, and 0.292, respectively, and the specificities were 0.722, 0.697, and 0.861, respectively. In addition, the predictive accuracy of the model was 0.827, the sensitivity was 0.829 and the specificity was 0.702 for stage‐1 PD. For stage‐2 PD, the predictive accuracy of the model was 0.854, the sensitivity was 0.960, and the specificity was 0.600.
Conclusion
Our results provide evidence that conventional structural MRI can predict the progression of PD. This work also supports the use of a simple radiomics signature built from whole‐brain white matter features as a useful tool for the assessment and monitoring of PD progression.
Abstract
In order to clarify the micro‐mechanics of clay during compression, the behavior of clay subjected to one‐dimensional compression is investigated at the particle scale using discrete element ...method (DEM). The flaky clay particles in the simulation are approximated by clumps made of spheres. A new contact model is implemented to account for the double‐layer repulsive force, the van der Waals attractive force and the mechanical contact force. The effect of sphere arrangement in the particle clump is discussed. The DEM model is validated against experimental observations in terms of macroscopic compressibility, particle dip angle as well as the over consolidated behavior. The
e
‐log
σ
v
curve shows a concave‐to‐linear shape. The evolution of dip angle of clay particles indicates that particles tend to have an anisotropy with a preferential orientation towards horizontal direction. The increase of preconsolidation pressure decreases the initial compressibility due to the increase the number of mechanical contacts. The evolution of average coordination and sphere‐sphere contact shows that the majority of mechanical contacts are generated before the compressive stress reaches 100 kPa. Evolution of soil fabric is presented and discussed.
Previous studies show that extensive particle breakage occurs at the soil-structure interface, which may influence the shear strength, but a corresponding comprehensive micro-mechanical analysis, ...particularly with constant normal stiffness (CNS), is missing. In this study, a series of interface shear tests under CNSs are simulated with the discrete element method (DEM) to understand the role of particle breakage at the interface. Through a rigorous calibration process, the interface model in DEM is first validated with identifying micro-mechanical parameters. Then, by modifying the reference tensile strength of particles, the effect of particle breakage on the behavior of soil-structure interface is quantitatively investigated. All results demonstrate that, particle breakage decreases the dilation, normal stress, shear stress, and shear zone thickness in the interface shear test; particle breakage decreases the peak friction angle while increases the residual friction angle at the interface; and particle breakage decreases soil anisotropy at the interface. In addition, the degree of particle breakage is increased by normal stiffness. The findings of this study may provide deeper insights on the role of particle breakage at the interface with CNS and allow engineers to have a better estimation of the interface strength.
Background
White matter hyperintensity (WMH) is widely observed in aging brain and is associated with various diseases. A pragmatic and handy method in the clinic to assess and follow up white matter ...disease is strongly in need.
Purpose
To develop and validate a radiomics nomogram for the prediction of WMH progression.
Study Type
Retrospective.
Population
Brain images of 193 WMH patients from the Picture Archiving and Communication Systems (PACS) database in the A Medical Center (Zhejiang Provincial People's Hospital). MRI data of 127 WMH patients from the PACS database in the B Medical Center (Zhejiang Lishui People's Hospital) were included for external validation. All of the patients were at least 60 years old.
Field Strength/Sequence
T1‐fluid attenuated inversion recovery images were acquired using a 3T scanner.
Assessment
WMH was evaluated utilizing the Fazekas scale based on MRI. WMH progression was assessed with a follow‐up MRI using a visual rating scale. Three neuroradiologists, who were blinded to the clinical data, assessed the images independently. Moreover, interobserver and intraobserver reproducibility were performed for the regions of interest for segmentation and feature extraction.
Statistical Tests
A receiver operating characteristic (ROC) curve, the area under the curve (AUC) of the ROC was calculated, along with sensitivity and specificity. Also, a Hosmer–Lemeshow test was performed.
Results
The AUC of radiomics signature in the primary, internal validation cohort, external validation cohort were 0.886, 0.816, and 0.787, respectively; the specificity were 71.79%, 72.22%, and 81%, respectively; the sensitivity were 92.68%, 87.94% and 78.3%, respectively. The radiomics nomogram in the primary cohort (AUC = 0.899) and the internal validation cohort (AUC = 0.84). The Hosmer–Lemeshow test showed no significant difference between the primary cohort and the internal validation cohort (P > 0.05). The AUC of the radiomics nomogram, radiomics signature, and hyperlipidemia in all patients from the primary and internal validation cohort was 0.878, 0.848, and 0.626, respectively.
Data Conclusion
This multicenter study demonstrated the use of a radiomics nomogram in predicting the progression of WMH with elderly adults (an age of at least 60 years) based on conventional MRI.
Level of Evidence: 3
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2020;51:535–546.
To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally‐advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy ...(CCRT). Using the NPC‐specific database from the established big‐data intelligence platform at Sun Yat‐Sen University Cancer Center, 583 non‐disseminated, locoregionally‐advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m2 after IC (range, 40‐300 mg/m2); only 74 patients (12.7%) achieved CCD >200 mg/m2. Patients receiving >200 mg/m2 CCD did not show significantly improved 5‐year overall survival (OS) (HR = 1.19; 95% confidence intervals CI 0.69‐2.06, P = .53) and progression‐free survival (PFS) (HR = 1.03; 95% CI: 0.63‐1.68, P = .92) compared with patients receiving <200 mg/m2 CCD. Further investigations of the potential of median CCD (160 mg/m2) to yield survival benefits revealed that there were no significant differences in survival endpoints between patients receiving CCD >160 mg/m2 and CCD < 160 mg/m2 in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein–Barr virus deoxyribonucleic acid (EBV DNA) <1000 copies/mL (HR = 0.26, 95% CI: 0.07‐0.93, P = .03) and receiving <3 IC cycles (HR = 0.59, 95% CI 0.33‐1.07, P = .08). Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving additional IC. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA <1000 copy/mL and receiving <3 IC cycles, a higher dose might be necessary.
Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving IC plus CCRT. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA < 1000 copy/mL, and receiving<3 IC cycles, higher dose might be necessary.
At present, there are various treatment strategies for colorectal cancer, including surgery, chemotherapy, radiotherapy, and targeted therapy. In recent years, with the continuous development of ...immunotherapy, immune checkpoint inhibitors (ICIs) can significantly improve the treatment of advanced colorectal cancer patients with high levels of microsatellite instability. In addition to ICIs, neoantigens, as a class of tumor-specific antigens (TSA), are regarded as new immunotherapy targets for many cancer species and are being explored for antitumor therapy. Immunotherapy strategies based on neoantigens include tumor vaccines and adoptive cell therapy (ACT). These methods aim to eliminate tumor cells by enhancing the immune response of host T-cells to neoantigens. In addition, for MSS colorectal cancer, such “cold tumors” with low mutation rates and stable microsatellites are not sensitive to ICIs, whereas neoantigens could provide a promising immunotherapeutic avenue. In this review, we summarized the current status of colorectal cancer neoantigen prediction and current clinical trials of neoantigens and discussed the difficulties and limitations of neoantigens-based therapies for the treatment of CRC.
The insecticide chlorantraniliprole exhibits good efifcacy and plays an important role in controlling the diamondback moth, Plutella xylostella Linnaeus. However, resistance to chlorantraniliprole ...has been observed recently in some ifeld populations. At present study, diamondback moths with resistance to chlorantraniliprole （resistant ratio （RR） was 82.18） for biochemical assays were selected. The assays were performed to determine potential resistance mechanisms. The results showed that the selected resistant moths （GDLZ-R） and susceptible moth could be synergized by known metabolic inhibitors such as piperonyl butoxide （PBO）, triphenyl phosphate （TPP） and diethyl-maleate （DEM） at different levels （1.68-5.50-fold and 2.20-2.89-fold, respectively）, and DEM showed the maximum synergism in both strains. In enzymes assays, a high level of glutathione-S-transferase （GST） was observed in the resistant moth, in contrast, moths that are susceptible to the insecticide had only 1/3 the GST activity of the resistant moths. The analysis of short-term exposure of chlorantraniliprole on biochemical response in the resistant strain also showed that GST activity was signiifcantly elevated after exposure to a sub-lethal concentration of chlorantraniliprole （about 1/3 LC50, 12 mg L-1） 12 and 24 h, respectively. The results show that there is a strong correlation between the enzyme activity and resistance, and GST is likely the main detoxiifcation mechanism responsible for resistance to chlorantraniliprole in P. xylostella L., cytochrome P450 monooxygenase （P450） and carboxy-lesterase （CarE） are involved in to some extent.
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