Rapid, reliable and easy-to-implement diagnostics that can be adapted in early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis are critical to combat the epidemic. SARS-CoV-2 ...nucleocapsid protein (NP) is an ideal target for viral antigen-based detection. A rapid and convenient method was developed based on fluorescence immunochromatographic (FIC) assay to detect the SARS-CoV-2 NP antigen. However, the accuracy of this diagnostic method needs to be examined.
This prospective study was carried out between 10 and 15 February 2020 in seven hospitals in Wuhan and one hospital in Chongqing, China. Participants with clinically suspected SARS-CoV-2 infection were enrolled. NP antigen testing by FIC assay and nucleic acid (NA) testing by real-time reverse transcriptase PCR (RT-PCR) were performed simultaneously in a blinded manner with the same nasopharyngeal swab sample. The diagnostic accuracy of NP antigen testing was calculated by taking NA testing of RT-PCR as the reference standard, in which samples with a cycle threshold (Ct) value of ≤40 were interpreted as positive for SARS-CoV-2.
A total of 253 participants were enrolled; two participants were excluded from the analyses because of invalid NP testing results. Of 251 participants (99.2%) included in the diagnostic accuracy analysis, 201 (80.1%) had a Ct value of ≤40. With Ct value 40 as the cutoff of NA testing, the sensitivity, specificity and percentage agreement of the FIC assay was 75.6% (95% confidence interval, 69.0–81.3), 100% (95% confidence interval, 91.1–100) and 80.5% (95% confidence interval, 75.1–84.9) respectively.
With RT-PCR assay as the reference standard, NP antigen testing by FIC assay shows high specificity and relatively high sensitivity in SARS-CoV-2 diagnosis in the early phase of infection.
Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect ...HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied.
A total of 14,861 samples were tested in Southwest Hospital in over 2 years' time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively.
A total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0-33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0-348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time.
Our data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.
The vehicle particle model was built to compare and analyze the effectiveness of three different collision avoidance methods. The results show that during vehicle high-speed emergency collision ...avoidance, lane change collision avoidance requires a smaller longitudinal distance than braking collision avoidance and is closer to that with a combination of lane change and braking collision avoidance. Based on the above, a double-layer control strategy is proposed to avoid collision when vehicles change lanes at high speed. The quintic polynomial is chosen as the reference path after comparing and analyzing three polynomial reference trajectories. The multiobjective optimized model predictive control is used to track the lateral displacement, and the optimization objective is to minimize the lateral position deviation, yaw rate tracking deviation, and control increment. The lower longitudinal speed tracking control strategy is to control the vehicle drive system and brake system to track the expected speed. Finally, the lane changing conditions and other speed conditions of the vehicle at 120 km/h are verified. The results show that the control strategy can track the longitudinal and lateral trajectories well and achieve effective lane change and collision avoidance.
Background Cholangiocarcinoma (CCA) is a typical inflammation-induced malignancy, and elevated serum interleukin-6 (IL-6) levels have been reported to be linked to the onset and progression of CCA. ...We aim to investigate the potential prognostic value of the IL-6 pathway for CCA. Methods We detected the expressions of IL-6, IL-6R, glycoprotein (gp130), C-reactive protein (CRP), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) in CCA tissue microarray using multiplex immunofluorescence. Furthermore, the clinical associations and prognostic values were assessed. Finally, single-cell transcriptome analysis was performed to evaluate the expression level of IL-6 pathway genes in CCA. Results The results revealed that the expression of IL-6 was lower, while the expression of STAT3 was higher in tumor tissues compared to normal tissues. Especially in tumor microenvironment, the expression of IL-6 pathway genes was generally downregulated. Importantly, gp130 was strongly correlated with JAK2 in tumor tissues, while it was moderately correlated with JAK2 in normal tissue. Although none of the gene expressions were directly associated with overall survival and disease-free survival, our study found that IL-6, IL-6R, CRP, gp130, and JAK2 were inversely correlated with vascular invasion, which is a risk factor for poor prognosis in patients with CCA. Conclusion The findings from this study suggest that the IL-6 signaling pathway may have a potential prognostic value for CCA. Further investigation is needed to understand the underlying molecular mechanisms of the IL-6 pathway in CCA.
For complex and dynamic high‐speed driving scenarios, an adaptive model predictive control (MPC) controller is designed to ensure effective path tracking for automated vehicles. Firstly, in order to ...prevent model mismatch in the MPC controller, a tire cornering stiffness estimation algorithm is designed and a soft constraint on slip angle is added to further enhance the controller's precision in tracking trajectories and the vehicle's driving stability. Secondly, the improved particle swarm optimization (IPSO) method with dynamic weights and penalty functions is suggested to address the issue of insufficient accuracy in solving quadratic programming. Additionally, the standard particle swarm optimization (PSO) algorithm is used to seek the most suitable time horizon parameters offline to obtain the best time horizon data set under different vehicle speeds and adhesion coefficients, and then it is optimized online by an adaptive network‐based fuzzy inference system (ANFIS) to enhance the model predictive controller's adaptability in different operating conditions. Finally, simulation experiments are conducted under three different operating conditions: docked roads, split roads, and variable vehicle speeds. The results indicate that the designed adaptive MPC controller can accurately and stably track the reference trajectory in various scenarios.
Here, the particle swarm optimization algorithm is used to find the optimal time horizon parameters of the model predictive control (MPC) under each speed and adhesion coefficient offline to form a dataset, which is then optimized online by adaptive network‐based fuzzy inference system to make the adaptive MPC adapt to different driving environments.
Autonomous driving technology in urban environments is a very important avenue of research. Notably, the question of how to plan safe lane-changing trajectories is a challenge in multi-vehicle ...traffic environments. In our research, three kinds of polynomial lane changing mathematical models were analyzed and compared. It was found that the fifth polynomial is the most suitable for lane changing trajectories; it is defined as a generalized lane-changing trajectory cluster, whereby the minimum lane change time is determined by the vehicle lateral stability threshold. Here, a collision avoidance algorithm is proposed to eliminate unsafe trajectories. Finally, the TOPSIS algorithm is used to solve the multi-objective optimization problem, and the optimal lane-changing expected trajectory is obtained from the safe trajectory cluster. The simulation results showed improvements in lane-changing efficiency of 6.67% and no collisions in the overtaking condition. In general, the proposed method of identifying the optimal lane changing trajectory can achieve safe, efficient and stable lane changing.
Crigler-Najjar Syndrome type II (CNS-II) is an autosomal recessive hereditary condition of unconjugated hyperbilirubinemia without hemolysis, with bilirubin levels ranging from 102.6 μmol/L to 342 ...μmol/L. CNS-II is caused by a deficiency of UDP-glucuronyl transferase (UGT), which is encoded by the UDP-glucuronyl transferase 1A1 gene (UGT1A1). In East Asian populations, the compound homozygous UGT1A1 G71R and Y486D variants are frequently observed in cases with bilirubin levels exceeding 200 μmol/L. In this study, we investigated the spectrum of UGT1A1 variations in Chinese CNS-II patients. We sequenced the enhancer, promoter, and coding regions of UGT1A1 in 11 unrelated Chinese CNS-II patients and 80 healthy controls. Nine of these patients carried variations that are here reported for the first time in CNS-II patients, although they have been previously reported for other types of hereditary unconjugated hyperbilirubinemia. These individual variations have less influence on UGT activity than do the compound homozygous variation (combination of homozygous G71R variant and Y486D variant). Therefore, we propose that the spectrum of UGT1A1 variations in CNS-II differs according to the bilirubin levels.
The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine ...confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10−3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.
Autonomous urban driving navigation is still an open problem and has ample room for improvement in unknown complex environments. This paper proposes an end-to-end autonomous driving approach that ...combines Conditional Imitation Learning (CIL), Mask R-CNN with DDPG. In the first stage, data acquisition is first performed by using CARLA, a high-fidelity simulation software. Data collected by CARLA is used to train the Mask R-CNN network, which is used for object detection and segmentation. The segmented images are transformed into the backbone of CIL to perform supervised Imitation Learning (IL). DDPG means using Reinforcement Learning for further training in the second stage, which shares the learned weights from the pre-trained CIL model. The combination of the two methods is an innovative way of considering. The benefit is that it is possible to speed up training considerably and obtain super-high levels of performance beyond humans. We conduct experiments on the CARLA driving benchmark of urban driving. In the final experiments, our algorithm outperforms the original MP by 30%, CIL by 33%, and CIRL by 10% in the most difficult tasks, dynamic navigation tasks, and in new environments and new weather, demonstrating that the two-stage framework proposed in this paper shows remarkable generalization capability in unknown environments on navigation tasks.
Host genetic factors such as single nucleotide variations may play a crucial role in the onset and progression of HBV-related acute-on-chronic liver failure (ACLF). However, the underlying genomic ...copy number variations (CNVs) involved in the pathology are currently unclear.
We genotyped two cohorts with 389 HBV-related ACLF patients and 391 asymptomatic HBV carriers (AsCs), and then carried out CNV-based global burden analysis and a genome-wide association study (GWAS).
For 1874 rare CNVs, HBV-related ACLF patients exhibited a high burden of deletion segments with a size of 100-200 kb (P value = 0.04), and the related genes were significantly enriched in leukocyte transendothelial migration pathway (P value = 4.68 × 10
). For 352 common CNVs, GWAS predicted 17 significant association signals, and the peak one was a duplication segment located on 1p36.13 (~ 38 Kb, P value = 1.99 × 10
, OR = 2.66). The associated CNVs resulted in more copy number of pro-inflammatory genes (MST1L, DEFB, and HCG4B) in HBV-related ACLF patients than in AsC controls.
Our results suggested that the impact of host CNV on HBV-related ACLF may be through decreasing natural immunity and enhancing host inflammatory response during HBV infection. The findings highlighted the potential importance of gene dosage on excessive hepatic inflammation of this disease.
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