The assist-as-needed (AAN) controller is effective in robot-assisted rehabilitation. However, variations of the engagement of subjects with fixed controller often lead to unsatisfying results. Therefore, adaptive AAN that adjusts control parameters based on individualized engagement is essential to enhance the training effect further. Nevertheless, current approaches mainly focus on the within-trial real-time engagement estimation, and the presence of measurement noise may cause improper evaluation of engagement. In addition, most studies on human-in-loop optimization strategies modulate the controller by greedy strategies, which are prone to fall into local optima. These shortcomings in previous studies could significantly limit the efficacy of AAN. This paper proposes an adaptive AAN to promote engagement by providing subjects with a subject-adaptive assistance level based on trial-wise engagement estimation and performance. Firstly, the engagement is estimated from energy information, which assesses the work done by the subject during a full trial to reduce the influence of measurement outliers. Secondly, the AAN controller is adapted by Bayesian optimization (BO) to maximize the subject’s performance according to historical trial-wise performance. The BO algorithm is good at dealing with noisy signals within limited steps. Experiments with ten healthy subjects resulted in a decrease of 34.59$\%$ in their average trajectory error, accompanied by a reduction of 9.71$\%$ in their energy consumption, thus verifying the superiority of the proposed method to prior work. These results suggest that the proposed method could potentially improve the effect of upper limb rehabilitation.

The southeastern Central Asian Orogenic Belt (CAOB) records the assembly process between several micro-continental blocks and the North China Craton (NCC), with the consumption of the Paleo-Asian Ocean (PAO), but whether the S-wards subduction of the PAO beneath the northern NCC was ongoing during Carboniferous–Permian time is still being debated. A key issue to resolve this controversy is whether the Carboniferous magmatism in the northern NCC was continental arc magmatism. The Alxa Block is the western segment of the northern NCC and contiguous to the southeastern CAOB, and their Carboniferous–Permian magmatism could have occurred in similar tectonic settings. In this contribution, new zircon U–Pb ages, elemental geochemistry and Sr–Nd isotopic analyses are presented for three early Carboniferous granitic plutons in the southwestern Alxa Block. Two newly identified aluminous A-type granites, an alkali-feldspar granite (331.6 ± 1.6 Ma) and a monzogranite (331.8 ± 1.7 Ma), exhibit juvenile and radiogenic Sr–Nd isotopic features, respectively. Although a granodiorite (326.2 ± 6.6 Ma) is characterized by high Sr/Y ratios (97.4–139.9), which is generally treated as an adikitic feature, this sample has highly radiogenic Sr–Nd isotopes and displays significantly higher K2O/Na2O ratios than typical adakites. These three granites were probably derived from the partial melting of Precambrian continental crustal sources heated by upwelling asthenosphere in lithospheric extensional setting. Regionally, both the Alxa Block and the southeastern CAOB are characterized by the formation of early Carboniferous extension-related magmatic rocks but lack coeval sedimentary deposits, suggesting a uniform lithospheric extensional setting rather than a simple continental arc.

Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5′UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.

The Figure 4 in the original version has a stylistic error.

It ought to use the figure as follows: The authors apologise for this error.

It is a challenging task for a human operator to manipulate a robot from a remote distance, especially in an unknown environment. Excellent teleoperation provides the human operator with a sense of telepresence, mainly including real-world vision, haptic perception, etc. This paper presents a novel virtual environment building method using the red–green–blue (RGB) colour information, the surface normal feature-based 3D-point-cloud registration method and the weighted sliding-average least-square-method-based real-world dynamic modelling for teleoperation. The experiments prove the method to be an accurate and effective means of teleoperation.

Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML) with microstructure changes of white matter (WM), and cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and to discuss the potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course ≥5 years and age ranging from 65 to 75 years old. A control group consisted of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML levels were measured by enzyme-linked immunosorbent assay, and cognitive function was assessed by Mini-Mental State Examination and Montreal cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group (25.72±3.13) was significantly lower than the control group (28.16±2.45) (p<0.05). In addition, the total MoCA score in the patient group (22.15±3.56) was significantly lower than the control group 25.63±4.12) (p<0.01). In the patient group, FA values were significantly decreased in the corpus callosum, cingulate fasciculus, inferior fronto-occipital fasciculus, parietal WM, hippocampus, and temporal lobes relative to corresponding regions of healthy controls (p<0.05). Plasma CML level was negatively correlated with average FA values in the global brain (r=−0.58, p<0.01) and MoCA scores (r=−0.47, p<0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and elevations in CML may play a role in the development of cognitive impairment.

5-AZA-2′-deoxycytidine (5-AZA-CdR) is a demethylating, teratogenic agent and a mutagen, which causes defects in the developing mouse and rat after implantation. Our previous data indicated that 5-AZA-CdR (0.2 and 1.0 μM) inhibited the development of mouse preimplantation embryos. Pronuclear embryos exposed to 5-AZA-CdR at the pronuclear stage were unable to form 8-cell embryos, while 2-cell-stage embryos exposed to 5-AZA-CdR only developed into uncompacted 8-cell-stage embryos. And there was no formation of blastocysts when 4-cell embryos cultured in 5-AZA-CdR. In our present study, we detected Dnmt1o protein and some developmental gene expression in order to find the reasons for the developmental arrest. Dnmt1o could not traffic to 8-cell nuclei as control when embryos were exposed to 5-AZA-CdR. Dnmt1o was in cytoplasm at 2-cell and 4-cell stages before and after treated with 5-AZA-CdR. Gene expression changes were also detected in this research. Our data indicated that connexin 31 (Cx31), connexin 43 (Cx43), connexin 45 (Cx45), E-cadherin (Cdh1) and β-catenin (Ctnnb1) were all downregulated by 5-AZA-CdR. Cx31, Cx43 and Cx45 are members of connexins family, which have a central role in gap junctions. Cdh1 and Ctnnb1 are necessary for the foundation of tight junctions. Therefore, developmental arrest induced by 5-AZA-CdR may be caused by the failure of Dnmt1o cytoplasmic–nuclear traffic and the down-regulation of developmental gene expression. Normal compaction and blastocoel cavitation need Dnmt1o traffic to 8-cell nuclei and the right gene expression, especially the correlative genes in gap junctions and tight junctions.