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Neural stem progenitor cell (NSPC) transplantation has been regarded as a promising therapeutic method for spinal cord injury (SCI) repair. However, different NSPCs may have different therapeutic effects, and it is therefore important to identify the optimal NSPC type. In our study, we compared the transcriptomes of human fetal brain-derived NSPCs (BNSPCs), spinal cord-derived NSPCs (SCNSPCs) and H9 embryonic stem-cell derived NSPCs (H9-NSPCs)

Current therapeutic regimens for patients with v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E-mutated colorectal cancer show unsatisfactory efficacy. To improve outcomes in this area, we assessed the safety and efficacy of a new protocol using vemurafenib and cetuximab combined with FOLFIRI (5-fluorouracil/leucovorin/irinotecan) in patients with BRAF V600E-mutated colorectal cancer.This was an investigator-initiated, open-label, single-arm, phase II trial conducted in patients with BRAF V600E-mutated advanced colorectal cancer. Patients were eligible to receive FOLFIRI combined with vemurafenib and cetuximab. The primary end-point was the objective response rate, and the secondary end-points included disease control rate, progression-free survival, overall survival and safety. This trial is registered with ClinicalTrials.gov, NCT03727763.Between 12th January 2018, and 18th June 2021, we screened 27 patients, 21 of which were enrolled in this study. Efficacy analysis showed that objective response rates were 81.0% (17/21; 95% confidence interval [CI] 57.4-93.7) in the intention-to-treat population and 85.0% (17/20, 95%CI 61.0-96.0) in the per-protocol population; two patients achieved complete response, and 15 patients achieved a partial response. In the entire cohort, the median progression-free survival was 9.7 months (95%CI 6.3-10.9), and the median overall survival for all patients was 15.4 months (95%CI 8.5-15.4). The most common adverse events (grade 3 to 4) were neutropenia (8/21), anaemia (3/21) and skin rash (3/21).Vemurafenib and cetuximab can be safely combined with the FOLFIRI regimen, showing promising antitumour activity and tolerable toxicity in patients with BRAF V600E-mutated advanced colorectal cancer. This regimen warrants a further randomised study in phase III clinical trials.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P

Laboratory experiments were conducted to define the response to earthquake loading of the exposed column-base connections common in low-rise steel frame structures. Six full-scale column-base connections with four internal anchor bolts were prepared and tested to failure under major- and minor-axis cyclic loading. The parameters varied were the size and thickness of the base plate and the diameter of the anchor bolts. The data were used to calibrate a finite element simulation, and that was used to predict the influence of other design parameters on the initial rotational stiffness of a connection. Linear regression was used to model the response surface of the initial rotational stiffness and the bending capacity of the connections under minor-axis loading. A three-parameter power function model was derived which acceptably predicted the experimental results.

Canonical correlation analysis (CCA) is an unsupervised representation learning technique to correlate multi-view data by learning a set of projection matrices. Being complementary with CCA, many discriminant methods are proposed to extract discriminative features of multi-view data by introducing the supervised class information. However, the learned projection matrices in these methods are mathematically constrained to be equal rank to the class number, and thus cannot represent the original data comprehensively. In this paper, we propose a general multi-view information fusion technique, named sparse additive discriminative canonical correlation analysis (SaDCCA). On one hand, SaDCCA is equipped with a strong degree of discrimination by defining a new affinity matrix that reflects the high-order characteristics of intra-class and the separability of inter-class. On the other hand, SaDCCA can exploit the correlation among multi-view data by maintaining the spirit of CCA. The discrimination among classes and the correlation among views are integrated in an additive manner. To obtain the sparse solutions, we first establish the relationship between the objective function and the underdetermined linear system equations, and then obtain the l 1 -norm solution by accelerated Bregman iteration with matrix form. SaDCCA has no rank constraint on the projection matrices and is capable to provide accurate recognition performance. Experiments conducted on some publicly available datasets demonstrate the effectiveness of the proposed approach.

To investigate the clinical outcome and factors affecting the prognosis of endovascular mechanical thrombectomy of acute vertebrobasilar artery occlusion.Eighty-three patients with acute vertebrobasilar artery occlusion were treated with endovascular mechanical thrombectomy, and the recanalization rate, clinical outcomes at three months, modified DWI-PC-ASPECTS, and MRA-BATMAN scores were analyzed.Following acute mechanical thrombectomy, the TICI 2B-3 score was achieved in all patients (100%). At three-month evaluation, 56 (67.5%) patients had good prognosis with the mRS score of 0-2, including 13 (23.2%) patients who had arterial occlusion caused by emboli and 43 (76.8%) who had atherosclerotic stenosis. In analyzing factors affecting the prognosis, a significant difference (P 0.05) existed between patients with good (mRS 0-2) and poor (mRS 3-6) prognosis in the NIHSS (17.3 vs. 31.2, P = 0.000001), modified DWI-PC-ASPECTS (10.4 vs. 7.8, P = 0.021), and MRA-BATMAN (6.3 vs. 4.6, P = 0.003) scores. Univariate Logistic regression analysis demonstrated NIHS score ≥ 21, modified DWI-PC-ASPECTS score ≤ 8.5, and MRA-BATMAN score ≤ 6.5 to be the risk factors for poor prognosis. Multivariate Logistic regression analysis revealed NIHSS score ≥ 21 as an independent risk factor for poor prognosis.Endovascular mechanical thrombectomy is safe and effective in recanalizing occluded vertebrobasilar artery occlusion, and NIHS score ≥ 21, modified DWI-PC-ASPECTS score ≤ 8.5, and MRA-BATMAN score ≤ 6.5 are the risk factors for poor prognosis.

To study the multi-stage seismic failure mode of semi-rigid plane steel frame with end-plate connection, one 1/2-scale specimen of the quasi-static cyclic test was conducted. According to the failure criteria, the mechanical characteristics and the failure process of the specimen at three performance stages (the elastic stage, the elastoplastic stage, and the ultimate stage) were studied. The bearing capacity, stiffness degradation, and the plastic energy dissipation of the test specimen were also analyzed. Moreover, a nonlinear finite element model of the specimen was implemented in the ABAQUS platform to compare and verify the test results, and a parametric analysis was conducted to investigate the influence of the thickness ratio (δ = te/tf) of the end-plate (te) to the column flange (tf) on frame performance. The specimen has reliable energy dissipation capacity and ductility, and the lateral displacement of the first story accounted for about 40% of the second story displacement, while this ratio increased to 50% in the ultimate stage. The increase of δ can significantly improve the lateral stiffness and bearing capacity of the specimens, but the ductility decreases gradually. The failure order of the specimen was the yield of the end-plate, the yield of the beam end, the buckling of the column base, and the failure of the whole frame, which indicated that the specimen satisfied the design criteria of “strong column weak beam”.

To explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD).Thirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted.STN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively.Bilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture.Open Science Framework: DOI 10.17605/OSF.IO/3EGRC.

In the current paper, we are concerned with waves propagating through the deformation of a thin elastic sheet between two incompressible and inviscid fluids, which are usually called hydroelastic waves in the literature to model deformable sheets interacting with surrounding fluids. The main purpose of the present study is to solve a basic question on the theoretical side, i.e. the local well-posedness issue. The problem is formulated by the full Euler equations (without the assumption of irrotationality) for fluids, combined with the Plotnikov-Toland model for the elastic sheet. Based on geometric considerations, we derive energy estimates and prove the local existence and uniqueness of solution for this system in n ( ⩾ 2 ) dimensions even if velocity fields are rotational.

Purpose Radiation therapy elicits profound alterations in gene expression in tumor cells. This study aims to determine the dynamic changes in the expression of immunity-associated genes in nasopharyngeal carcinoma (NPC) cells upon radiation therapy. Methods and materials The study was performed using NPC patient-derived tumor xenograft tumors, cell lines, CCR4+ CD8 T cells sorted from peripheral blood mononuclear cells of healthy volunteers, and TCGA-derived bulk RNA-seq or single-cell RNA-seq (scRNA-seq) data sets. Patient-derived tumor xenograft tumors or cell lines were irradiated and collected for bulk RNA sequencing or for CCL22 expression and release detection. Malignant phenotypes and radiosensitivity were assessed in cells with or without overexpression of CCL22 or recombinant CCL22 treatment in the presence or absence of irradiation. TCGA data sets were used for uncovering CCR4 status in subtypes of T cells. CCL22 in supernatants, cell lysates, or serum samples was measured with enzyme-linked immunosorbent assay. Results CCL22 was significantly increased in the irradiated patient-derived tumor xenograft tumors, the supernatants and cell lysates collected from irradiated NPC cell lines, and the serum of patients who received radiation therapy. No alterations of malignant phenotypes were found in tumor cells with CCL22 overexpression or recombinant CCL22 treatment. Kaplan-Meier analysis revealed that CCL22 or its receptor CCR4 positively correlated with cytotoxic T lymphocyte signatures, and high expression of CCL22 or CCR4 was associated with better prognosis for patients with NPC. scRNA-seq data set-based analysis demonstrated that CCR4 was expressed in multiple subtypes of T cells, including effector CD8 T cells. Chemotaxis assay indicated that CCR4+ CD8 T cells could be recruited by CCL22 treatment. Conclusion The radiation-enhanced release of CCL22 from NPC cells promotes migration of CCR4 + effector CD8 T cells, which might partially be associated with radiation therapy-mediated antitumor immunity.

It is well known that the conjugate gradient algorithm is one of the most classic and useful methods for solving large-scale optimization problems, where the Polak-Ribiere-Polyak(PRP) method is an important and effective conjugate gradient algorithm. However, the global convergence of the PRP conjugate gradient method can not be achieved when the WWP line search technique is used for a nonconvex function. In this paper, we propose a modified WWP line search technique for the PRP conjugate gradient algorithm. The new line search technique can guarantee the global convergence of the PRP method for general functions. The numerical results show that the PRP method with a new line search technique enables a practical computation and is effective in the image restoration problems.

This paper presents a semi-analytical approach to investigate wave propagation characteristics in functionally graded graphene reinforced piezoelectric composite plates. Three patterns of graphene platelets (GPLs) describe the layer-wise variation of material properties in the thickness direction. Based on the Reissner-Mindlin plate theory and the isogeometric analysis, elastodynamic wave equation for the piezoelectric composite plate is derived by Hamilton’s principle and parameterized with the non-uniform rational B-splines (NURBS). The equation is transformed into a second-order polynomial eigenvalue problem with regard to wave dispersion. Then, the semi-analytical approach is validated by comparing with the existing results and the convergence on computing dispersion behaviors is also demonstrated. The effects of various distributions, volume fraction, size parameters and piezoelectricity of GPLs as well as different geometry parameters of the composite plate on dispersion characteristics are discussed in detail. The results show great potential of graphene reinforcements in design of smart composite structures and application for structural health monitoring.

Audio–visual emotion recognition is a challenging problem in the research fields of human–computer interaction and pattern recognition. Seeking a common subspace among the heterogeneous multi-modal data is essential for audio–visual emotion recognition. In this paper, we study the subspace learning for audio–visual emotion recognition by combing the similarity of intra-modality and the correlation of inter-modality. First, we enforce a low-rank constraint on the self-representation of the features in the subspace to exploit the structural similarity of intra-modality. It is based on a key observation that each modality and the corresponding features usually lie in a low-dimensional manifold. Second, we propose a joint low-rank model on the representation of inter-modality to keep consistency across different modalities. Finally, the intra-modality similarity and inter-modality correlation are integrated within a unified framework, for which we develop an efficient computational algorithm to pursue the common subspace. Experimental results on three typical audio–visual emotion datasets demonstrate the superior performance of our method on audio–visual emotion recognition.

Background and aims Dietary long-chain (≥20 carbons) n-3 polyunsaturated fatty acids (PUFAs) reduce atherosclerosis and enhance macrophage autophagy activation. How macrophage autophagy impacts atherosclerotic progression, particularly when comparing dietary n-3 PUFA supplementation vs. saturated fat feeding, is unknown. Methods We generated myeloid-specific autophagy-deficient and control mice in the Ldlr−/− background by transplanting bone marrow from myeloid-specific autophagy-related (atg) 5 knockout mice and wild type controls into irradiated Ldlr−/− recipients. After 7 weeks for recovery from radiation, mice were fed an atherogenic diet containing 0.2% cholesterol and 20% calories as palm oil (PO diet), or 10% calories as PO plus 10% calories as fish oil (FO diet) for 16 weeks. Results Compared to PO, FO significantly reduced plasma cholesterol, triglyceride, hepatic neutral lipid, and aortic caspase-1 cleavage, but increased aortic efferocytosis, leading to attenuated atherosclerosis in Ldlr−/− mice receiving wild type bone marrow. Myeloid atg5 deletion had little impact on plasma lipid concentrations and hepatic neutral lipid content, regardless of diet. Myeloid atg5 deletion increased aortic caspase-1 cleavage, decreased aortic efferocytosis and worsened atherosclerosis only in the FO-fed Ldlr−/− mice. Conclusions Deficient myeloid autophagy significantly attenuated FO-induced atheroprotection, suggesting that dietary n-3 PUFAs reduce atherosclerosis, in part, by activation of macrophage autophagy.