Signature construction and molecular subtype identification based on liver-specific genes for prediction of prognosis, immune activity, and anti-cancer drug sensitivity in hepatocellular carcinoma.

BACKGROUND: Liver specific genes (LSGs) are crucial for hepatocyte differentiation and maintaining normal liver function. A deep understanding of LSGs and their heterogeneity in hepatocellular carcinoma (HCC) is necessary to provide clues for HCC diagnosis, prognosis, and treatment. METHODS: The bulk and single-cell RNA-seq data of HCC were downloaded from TCGA, ICGC, and GEO databases. Through unsupervised cluster analysis, LSGs-based HCC subtypes were identified in TCGA-HCC samples. The prognostic effects of the subtypes were investigated with survival analyses. With GSVA and Wilcoxon test, the LSGs score, stemness score, aging score, immune score and stromal score of the samples were estimated and compared. The HCC subtype-specific genes were identified. The subtypes and their differences were validated in ICGC-HCC samples. LASSO regression analysis was used for key gene selection and risk model construction for HCC overall survival. The model performance was estimated and validated. The key genes were validated for their heterogeneities in HCC cell lines with quantitative real-time PCR and at single-cell level. Their dysregulations were investigated at protein level. Their correlations with HCC response to anti-cancer drugs were estimated in HCC cell lines. RESULTS: We identified three LSGs-based HCC subtypes with different prognosis, tumor stemness, and aging level. The C1 subtype with low LSGs score and high immune score presented a poor survival, while the C2 subtype with high LSGs score and immune score indicated an enduring survival. Although no significant survival difference between C2 and C3 HCCs was shown, the C2 HCCs presented higher immune score and stroma score. The HCC subtypes and their differences were confirmed in ICGC-HCC dataset. A five-gene prognostic signature for HCC survival was constructed. Its good performance was shown in both the training and validation datasets. The five genes presented significant heterogeneities in different HCC cell lines and hepatocyte subclusters. Their dysregulations were confirmed at protein level. Furthermore, their significant associations with HCC sensitivities to anti-cancer drugs were shown. CONCLUSIONS: LSGs-based HCC subtype classification and the five-gene risk model might provide useful clues not only for HCC stratification and risk prediction, but also for the development of more personalized therapies for effective HCC treatment.

Brain network reconfiguration for language and domain-general cognitive control in bilinguals.

For bilinguals, language control is needed for selecting the target language during language production. Numerous studies have examined the neural correlates of language control and shown a close relationship between language control and domain-general cognitive control. However, it remains unknown how these brain regions coordinate with each other when bilinguals exert cognitive control over linguistic and nonlinguistic representations. We addressed this gap using an extended unified structural equation modeling (euSEM) approach. Sixty-five Chinese-English bilinguals performed language switching and nonverbal switching tasks during functional magnetic resonance imaging (fMRI) scanning. The results showed that language control was served by a cooperative brain network, including the frontal lobe, the parietal cortex, subcortical areas, and the cerebellum. More importantly, we found that language control recruited more subcortical areas and connections from frontal to subcortical areas compared with domain-general cognitive control, demonstrating a reconfigurable brain network. In addition, the reconfiguration efficiency of the brain network was mainly determined by general cognitive ability but was also mediated by second language (L2) proficiency. These findings provide the first data-driven connectivity model that specifies the brain network for language control in bilinguals and also shed light on the relationship between language control and domain-general cognitive control.

The relationship between semantic access and introspective awareness.

There have long been speculations about the relationship between consciousness and language. This study aimed to determine whether an individual's level of introspective awareness, based on self-report, relates to accessibility of their semantic system as evaluated by the N400. Thirty-five university students completed the study. All were right-handed, with normal or corrected-to-normal vision, without known neurological or psychological health issues. They first performed on a lexical decision task while their brain electrophysiological responses were recorded. Then, they provided assessment ratings about their levels of introspective awareness. Analysis revealed moderate to strong correlations (Pearson's rs = 0.49-0.62) between awareness self-ratings and ease of semantic access as indexed by the N400. Correlation between the self-report measure and the objective neurophysiological measure suggests that subjective assessment of awareness may deserve more credibility, which in addition to reflecting subjective perception and evaluation about one's own higher order mental functioning, may also interact with the neurophysiological processes contributive and subject to such awareness. Implications for future research on the role of semantic network in the mechanism of introspective awareness are discussed.

Short-term language switching training tunes the neural correlates of cognitive control in bilingual language production.

The present study investigated how language switching experience would modulate the neural correlates of cognitive control involved in bilingual language production. A group of unbalanced Chinese-English bilinguals undertook an 8-day cued picture naming training during which they named pictures in either of their languages based on visually presented cues. Participants' brain activation was scanned before and after the training in the same task. Behavioral results revealed a significant training effect such that switch costs were reduced after training. fMRI results showed that after training, activation of brain areas associated with cognitive control including the anterior cingulated cortex and the caudate was reduced. Besides, the activation reduction in the left dorsal anterior cingulated cortex positively correlated with the reduction in switch costs in response time and this training effect could be transferred to untrained stimuli. These findings suggest that neural correlates of cognitive control, especially that of the conflict monitoring process, in bilingual language production could be modulated by short-term language switching training. Hum Brain Mapp 38:5859-5870, 2017. © 2017 Wiley Periodicals, Inc.

Imageability and semantic association in the representation and processing of event verbs.

This study examined the relative salience of imageability (the degree to which a word evokes mental imagery) versus semantic association (the density of semantic network in which a word is embedded) in the representation and processing of four types of event verbs: sensory, cognitive, speech, and motor verbs. ERP responses were recorded, while 34 university students performed on a lexical decision task. Analysis focused primarily on amplitude differences across verb conditions within the N400 time window where activities are considered representing meaning activation. Variation in N400 amplitude across four types of verbs was found significantly associated with the level of imageability, but not the level of semantic association. The findings suggest imageability as a more salient factor relative to semantic association in the processing of these verbs. The role of semantic association and the representation of speech verbs are also discussed.

T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response.

Sepsis is an excessive inflammatory condition with a high mortality rate and limited prediction and therapeutic options. In this study, for the first time, to our knowledge, we found that downregulation and/or blockade of T cell Ig and mucin domain protein 3 (Tim-3), a negative immune regulator, correlated with severity of sepsis, suggesting that Tim-3 plays important roles in maintaining the homeostasis of sepsis in both humans and a mouse model. Blockade and/or downregulation of Tim-3 led to increased macrophage activation, which contributed to the systemic inflammatory response in sepsis, whereas Tim-3 overexpression in macrophages significantly suppressed TLR-mediated proinflammatory cytokine production, indicating that Tim-3 is a negative regulator of TLR-mediated immune responses. Cross-talk between the Tim-3 and TLR4 pathways makes TLR4 an important contributor to Tim-3-mediated negative regulation of the innate immune response. Tim-3 signaling inhibited LPS-TLR4-mediated NF-κB activation by increasing PI3K-AKT phosphorylation and A20 activity. This negative regulatory role of Tim-3 reflects a new adaptive compensatory and protective mechanism in sepsis victims, a finding of potential importance for modulating innate responses in these patients.

Enhancing legibility in educational settings: Optimizing projection illuminance for varied indoor ambient illuminance.

Projectors are common display devices in the educational setting. However, dim projector lightbulbs or well-lit classrooms may cause blurriness in the projected image. To determine the optimal projection light under different ambient light conditions, the conjoint effects of projection illuminance and ambient illuminance on the legibility of projection images indoors were investigated. Participants (N = 96) were randomly assigned to one of six indoor ambient light conditions (0, 40, 80, 120, 160, and 200 lx) and performed a visual search task under several projection illuminance conditions (200, 250, 300, 350, and 400 lx). The accuracy and correct response time on the task were collected to evaluate the participants' visual performance to represent legibility. The optimal projection illuminance (high visual accuracy and fast reaction) was 400 lx (944 ANSI lumen) under all ambient light conditions. To avoid low legibility (accuracy<0.6) and maintain acceptable legibility (accuracy>0.7), the projection illuminance should be increased as the indoor ambient light increases.

Construction of a novel nomogram based on competing endogenous RNAs and tumor-infiltrating immune cells for prognosis prediction in elderly patients with colorectal cancer.

Competitive endogenous RNAs (ceRNAs) and tumor-infiltrating immune cells play essential roles in colorectal cancer (CRC) tumorigenesis. However, their prognostic role in elderly patients with CRC is unclear. Gene expression profiles and clinical information for elderly patients with CRC were downloaded from The Cancer Genome Atlas. Univariate, LASSO, and multivariate Cox regression analyses were utilized for screening key ceRNAs and prevent overfitting. A total of 265 elderly patients with CRC were included. We constructed a novel ceRNA network consisting of 17 lncRNAs, 35 miRNAs, and 5 mRNAs. We established three prognosis predictive nomograms based on four key ceRNAs (ceRNA nomogram), five key immune cells (immune cell nomogram), and their combination (ceRNA-immune cell nomogram). Among them, the ceRNA-immune cell nomogram had the best accuracy. Furthermore, the areas under the curve of the ceRNA-immune cell nomogram were also significantly greater than the TNM stage at 1 (0.818 vs. 0.693), 3 (0.865 vs. 0.674), and 5 (0.832 vs. 0.627) years. Co-expression analysis revealed that CBX6 was positively correlated with activated dendritic cells (R = 0.45, p < 0.01), whereas negatively correlated with activated mast cells (R =- 0.43, p < 0.01). In conclusion, our study constructed three nomograms to predict prognosis in elderly patients with CRC, among which the ceRNA-immune cell nomogram had the best prediction accuracy. We inferred that the mechanism underlying the regulation of activated dendritic cells and mast cells by CBX6 might play a crucial role in tumor development and prognosis of elderly patients with CRC.

Plant and Disease Recognition Based on PMF Pipeline Domain Adaptation Method: Using Bark Images as Meta-Dataset.

Efficient image recognition is important in crop and forest management. However, it faces many challenges, such as the large number of plant species and diseases, the variability of plant appearance, and the scarcity of labeled data for training. To address this issue, we modified a SOTA Cross-Domain Few-shot Learning (CDFSL) method based on prototypical networks and attention mechanisms. We employed attention mechanisms to perform feature extraction and prototype generation by focusing on the most relevant parts of the images, then used prototypical networks to learn the prototype of each category and classify new instances. Finally, we demonstrated the effectiveness of the modified CDFSL method on several plant and disease recognition datasets. The results showed that the modified pipeline was able to recognize several cross-domain datasets using generic representations, and achieved up to 96.95% and 94.07% classification accuracy on datasets with the same and different domains, respectively. In addition, we visualized the experimental results, demonstrating the model's stable transfer capability between datasets and the model's high visual correlation with plant and disease biological characteristics. Moreover, by extending the classes of different semantics within the training dataset, our model can be generalized to other domains, which implies broad applicability.

Impact of simulated microgravity on microvascular endothelial cell apoptosis.

Cardiovascular deconditioning is known to occur in astronauts exposed to microgravity. Endothelial dysfunction at microcirculatory sites might contribute to cardiovascular deconditioning induced by weightlessness. Recent studies have reported changes in the morphology and gene expression of endothelial cells exposed to conditions of simulated microgravity. The present study was aimed at examining the effects of microgravity on the apoptosis of microvascular endothelial cells and the mechanism underlying these effects. We simulated a microgravity environment and found that microgravity induced microvascular endothelial cell apoptosis and that this effect was correlated with the downregulation of the PI3K/Akt pathway, increased expression of NF-κB, and depolymerization of F-actin. These findings may provide important insights into the origin of the adverse physiological changes occurring due to exposure to microgravity conditions.

Construction and Validation of a Lung Cancer Diagnostic Model Based on 6-Gene Methylation Frequency in Blood, Clinical Features, and Serum Tumor Markers.

Lung cancer has a high mortality rate. Promoting early diagnosis and screening of lung cancer is the most effective way to enhance the survival rate of lung cancer patients. Through computer technology, a comprehensive evaluation of genetic testing results and basic clinical information of lung cancer patients could effectively diagnose early lung cancer and indicate cancer risks. This study retrospectively collected 70 pairs of lung cancer tissue samples and normal human tissue samples. The methylation frequencies of 6 genes (FHIT, p16, MGMT, RASSF1A, APC, DAPK) in lung cancer patients, the basic clinical information, and tumor marker levels of these patients were analyzed. Then, the python package "sklearn" was employed to build a support vector machine (SVM) classifier which performed 10-fold cross-validation to construct diagnostic models that could identify lung cancer risk of suspected cases. Receiver operation characteristic (ROC) curves were drawn, and the performance of the combined diagnostic model based on several factors (clinical information, tumor marker level, and methylation frequency of 6 genes in blood) was shown to be better than that of models with only one pathological feature. The AUC value of the combined model was 0.963, and the sensitivity, specificity, and accuracy were 0.900, 0.971, and 0.936, respectively. The above results revealed that the diagnostic model based on these features was highly reliable, which could screen and diagnose suspected early lung cancer patients, contributing to increasing diagnosis rate and survival rate of lung cancer patients.

Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma.

Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient's plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels.

Optimal Time Intervals in Two-Stage Takeover Warning Systems With Insight Into the Drivers' Neuroticism Personality.

Conditional automated driving [level 3, Society of Automotive Engineers (SAE)] requires drivers to take over the vehicle when an automated system's failure occurs or is about to leave its operational design domain. Two-stage warning systems, which warn drivers in two steps, can be a promising method to guide drivers in preparing for the takeover. However, the proper time intervals of two-stage warning systems that allow drivers with different personalities to prepare for the takeover remain unclear. This study explored the optimal time intervals of two-stage warning systems with insights into the drivers' neuroticism personality. A total of 32 drivers were distributed into two groups according to their self-ratings in neuroticism (high vs. low). Each driver experienced takeover under the two-stage warning systems with four time intervals (i.e., 3, 5, 7, and 9 s). The takeover performance (i.e., hands-on-steering-wheel time, takeover time, and maximum resulting acceleration) and subjective opinions (i.e., appropriateness and usefulness) for time intervals and situation awareness (SA) were recorded. The results showed that drivers in the 5-s time interval had the best takeover preparation (fast hands-on steering wheel responses and sufficient SA). Furthermore, both the 5- and 7-s time intervals resulted in more rapid takeover reactions and were rated more appropriate and useful than the 3- and 9-s time intervals. In terms of personality, drivers with high neuroticism tended to take over immediately after receiving takeover messages, at the cost of SA deficiency. In contrast, drivers with low neuroticism responded safely by judging whether they gained enough SA. We concluded that the 5-s time interval was optimal for drivers in two-stage takeover warning systems. When considering personality, drivers with low neuroticism had no strict requirements for time intervals. However, the extended time intervals were favorable for drivers with high neuroticism in developing SA. The present findings have reference implications for designers and engineers to set the time intervals of two-stage warning systems according to the neuroticism personality of drivers.

Lung cancer A549 cells suppressed with overexpressed HNF1B or PCDHA13 inhibited PI3K/AKT phosphorylation.

BACKGROUND: Lung cancer is the most revenant and deadly tumors around the world. Here we aimed to explore the effects of hepatocyte nuclear factor 1B (HNF1B) and PCDHA13 overexpression on PI3K/AKT phosphorylation and malignant biological behavior in lung cancer A549 cells. METHODS: HNF1B and PCDHA13 were amplified, and their overexpression plasmids were constructed for transfection. RT-PCR was used to detect the mRNA levels of HNF1B and PCDHA13. Cell proliferation and cell apoptosis were detected by clone formation experiments and flow cytometry, respectively, while cell invasion was studied by Transwell assay. The expression of survivin, PCNA, Caspase-3, Caspase-9, VEGF, and fibronectin was detected using immunoblotting, as was PI3K/AKT phosphorylation. RESULTS: The level of HNF1B mRNA expression was significantly higher in the pcNDA-HNF1B group than in the control group (P<0.05), and the level of PCDHA13 mRNA expression in the pcNDA-PCDHA13 group was also significantly increased (P<0.05). The clone formation rate and cell invasion count in pcNDA-HNF1B or pcNDA-PCDHA13 transfected groups were significantly reduced in comparison with the control group, which were further validated with the protein expression levels of survivin, PCNA, VEGF, and fibronectin (P<0.05). However, the apoptosis rate, and the cleaved caspase3/caspase3 and cleaved caspase9/caspase9 protein expression ratios were all significantly increased (P<0.05). Cells transfected with pcNDA-HNF1B or pcNDA-PCDHA13 showed decreased levels of PI3K/AKT phosphorylation (P<0.05). CONCLUSIONS: Overexpression of HNF1B and PCDHA13 inhibits the phosphorylation of PI3K/AKT and hinders the malignant biological behavior of lung cancer A549 cells.

Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness.

BACKGROUND: Betulinic acid (BA) is a lupine pentacyclic triterpene compound derived from the bark of the white mulberry tree, which has a variety of pharmacological properties. The purpose of this study was to investigate the effects of BA combined with cisplatin on the proliferation, stemness, pyroptosis, and xenograft growth of esophageal carcinoma cells in a nude mouse xenograft model. METHODS: The cell survival rate was detected by CCK-8 method. TE-11 cells were treated with 3µM of BA and 15 µM of cisplatin. The cells were randomly divided into four groups: the control group, the BA group, the cisplatin group, and the BA + Cisplatin group. Western blotting was used to detect the expression levels of Ki67, PCNA, SOX2, OCT4, ASC, and Caspase-1. The xenograft model of nude mice was constructed to detect tumor volume, and the positive expression rates of Ki67 and Caspase-1 were detected by immunohistochemistry. RESULTS: Compared with the control group, Ki67, PCNA, SOX2, and OCT4 levels in the BA and cisplatin groups were significantly lower (P<0.05), while ASC and Caspase-1 levels were significantly higher (P<0.05). Compared with the BA group, Ki67, PCNA, SOX2, and OCT4 levels in the BA + cisplatin group were significantly lower (P<0.05), while ASC and Caspase-1 levels were significantly higher (P<0.05). In the nude mouse xenograft model, compared with the control group, the tumor volume of the BA and cisplatin groups was significantly decreased (P<0.05), the expression rate of Ki67 was significantly decreased (P<0.05), and the expression rate of Caspase-1 was significantly increased (P<0.05). Compared with the BA group, the levels of ASC and Caspase-1 in the BA + cisplatin group were significantly lower (P<0.05), the positive expression rate of Ki67 was significantly lower (P<0.05), and the positive expression rate of Caspase-1 was significantly higher (P<0.05). CONCLUSIONS: BA enhances the chemical sensitivity of esophageal cancer cells to cisplatin by inhibiting cell proliferation, reducing cell stemness, and inducing pyroptosis.

A chalcone inhibits the growth and metastasis of KYSE-4 esophageal cancer cells.

OBJECTIVE: To investigate the in vitro and in vivo anticancer effects of a chalcone against KYSE-4 esophageal cancer cells. METHODS: A chalcone was synthesized via the molecular hybridization strategy based on the anticancer activity of chalcone and dithiocarbamate scaffolds. The anticancer effects of different concentrations of the chalcone derivative were compared in esophageal cancer cells. RESULTS: This chalcone displayed strong inhibitory effects on esophageal cancer cell growth with an IC50 of 1.06 µM in KYSE-4 cells. Analysis of the mechanism revealed that the derivative obviously inhibited KYSE-4 cell growth, migration, and invasion in a concentration-dependent manner. Furthermore, the compound regulated migration-related biomarkers (E-cadherin, N-cadherin, and Slug) and inhibited the Wnt/ß-catenin pathway. According to western blotting, this chalcone suppressed the expression of proline-rich protein 11 (PRR11) in a concentration- and time-dependent manner. CONCLUSIONS: This chalcone might be a leading candidate for suppressing the growth and metastasis of esophageal cancer by downregulating PRR11 expression and inhibiting Wnt/ß-catenin signaling.

Promote or inhibit: An inverted U-shaped effect of workload on driver takeover performance.

OBJECTIVE: In conditional automated driving (SAE Level 3), drivers are required to take over their vehicles when the automated systems fail. Non-driving related tasks (NDRTs) can positively or negatively affect takeover safety, but the underlying reasons for this inconsistency remain unclear. This study aims to investigate how various workload levels generated by NDRTs may influence the takeover performance of drivers and the lead time they require. METHOD: Fifty drivers were randomly distributed into five groups, which corresponded to five workload levels (1-4 levels generated by Tetris game; control level generated by monitoring). Each driver completed vehicle takeover tasks upon receiving takeover requests with various lead times (3, 5, 7, 9, and 11 s) while engaging in NDRTs. The drivers' takeover performance and subjective opinions were recorded. RESULTS: Drivers in the moderate workload condition (i.e., level 3) had significantly shorter takeover times and better takeover quality than those in the lower (i.e., level 1 and level 2) or higher (i.e., level 4) workload conditions. They also subjectively required less lead time in the moderate condition. Moreover, the drivers rated 7 s as the most appropriate lead time despite the improvement in their overall takeover performances with increased lead time. CONCLUSIONS: This study found an inverted U-shaped relationship between the drivers' workload generated by NDRTs and takeover performance. The moderate workload level (rather than the lower or higher workload level) led to a faster and better takeover performance, and it seemed to require minimal lead time for drivers. These findings help understand the relationship of drivers' workload during the automation and takeover performance in conditional automated driving. An important recommendation emerging from this work is to investigate what should be the most efficient method to detect the drivers' workload state real-time and give feedback to them when it comes to overload or underload during the automated driving.

PRR11 and SKA2 promote the proliferation, migration and invasion of esophageal carcinoma cells.

Proline-rich protein 11 (PRR11) together with its upstream adjacent gene, spindle and kinetochore associated 2 (SKA2), represent a classic, head-to-head gene pair. The role of the PRR11 and SKA2 gene pair has been described in various types of cancer, including breast cancer, non-small cell lung cancer, hepatocellular carcinoma and ovarian carcinoma. However, its role in esophageal carcinoma (ESCC) remains unclear. The mRNA expression levels of PRR11 and SKA2 were examined in ESCC surgical specimens. In addition, the role of PRR11 and SKA2 in the proliferation and migratory and invasive capacities of EC9706 and EC109 cell lines was examined. The results from the present study demonstrated that PRR11 and SKA2 expression levels were upregulated in ESCC tissues compared with adjacent normal tissues. Furthermore, PRRl1 and SKA2 knockdown significantly inhibited the proliferation and migratory and invasive capacities of ESCC cells. Conversely, PRRl1 and SKA2 overexpression significantly promoted the proliferation and migratory and invasive capacities of ESCC cell lines via activation of the AKT signaling pathway and certain markers of epithelial-mesenchymal transition, including Snail and N-cadherin. The results from the present study suggested that the PRR11 and SKA2 gene pair may represent a potential target in the diagnosis and treatment of ESCC.

Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.

BACKGROUND: Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression. METHODS: The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis. RESULTS: Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed. CONCLUSION: The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.

Influences of Augmented Reality Assistance on Performance and Cognitive Loads in Different Stages of Assembly Task.

According to the assembly task model proposed by Stork and Schubö (2010), the assembly task is divided into commissioning and joining subtasks. Each subtask includes two sequential stages, namely, perception and response selection, and action. This division enables a convenient discussion of the influences of Augmented reality (AR) assistance on operators during different stages of an assembly task. Research results can provide a basis for the further analysis of the influence mechanism of AR assistance on an assembly task. This study is composed of three experiments. Experiment 1 explores the influences of AR assistance on the performance of the overall assembly task and the commissioning and joining subtasks. Combining a variation of task complexities, Experiments 2 and 3 discuss the influences of AR assistance on the different stages of the commissioning and joining subtasks. We found that AR assistance can shorten the time of the overall assembly task and subtasks (commissioning and joining) and reduce mistakes during these tasks. Moreover, AR assistance can decrease cognitive load in the commissioning subtask, but it increases cognitive load in the joining task with low complexity. In the perception and response selection stage of the commissioning and joining subtasks, AR assistance can shorten the time for users to recognize the target part and understand the assembly relation. This advantage is extremely significant for the high-complexity task. In the action stage of two subtasks, AR assistance can shorten the time for users to capture parts, but it prolongs the time for users to build parts.