Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

OBJECTIVE: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. METHODS: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. RESULTS: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 µ m and 182 µ m , respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 µ m in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. CONCLUSIONS: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. CLINICAL RELEVANCE STATEMENT: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. KEY POINTS: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 µ m in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

NDRG1 facilitates self-renewal of liver cancer stem cells by preventing EpCAM ubiquitination.

BACKGROUND: Portal vein tumour thrombus (PVTT) is the main pathway of HCC intrahepatic metastasis and is responsible for the poor prognosis of patients with HCC. However, the molecular mechanisms underlying PVTT vascular metastases have not been fully elucidated. METHODS: NDRG1 expression was assessed by immunohistochemistry and immunoblotting in clinical specimens obtained from curative surgery. The functional relevance of NDRG1 was evaluated using sphere formation and animal models of tumorigenicity and metastasis. The relationship between NDRG1 and EpCAM was explored using molecular biological techniques. RESULTS: NDRG1 protein was upregulated in HCC samples compared to non-tumorous tissues. Furthermore, NDRG1 expression was enhanced in the PVTT samples. Our functional study showed that NDRG1 was required for the self-renewal of tumour-initiating/cancer stem cells (CSCs). In addition, NDRG1 knockdown inhibited the proliferation and migration of PVTT-1 cells in vitro and in vivo. NDRG1 was found to stabilise the functional tumour-initiating cell marker EpCAM through protein-protein interactions and inhibition of EpCAM ubiquitination. CONCLUSION: Our findings suggest that NDRG1 enhances CSCs expansion, PVTT formation and growth capability through the regulation of EpCAM stability. NDRG1 may be a promising target for the treatment of patients with HCC and PVTT.

Topic Discovery and Hotspot Analysis of Sentiment Analysis of Chinese Text Using Information-Theoretic Method.

Currently, sentiment analysis is a research hotspot in many fields such as computer science and statistical science. Topic discovery of the literature in the field of text sentiment analysis aims to provide scholars with a quick and effective understanding of its research trends. In this paper, we propose a new model for the topic discovery analysis of literature. Firstly, the FastText model is applied to calculate the word vector of literature keywords, based on which cosine similarity is applied to calculate keyword similarity, to carry out the merging of synonymous keywords. Secondly, the hierarchical clustering method based on the Jaccard coefficient is used to cluster the domain literature and count the literature volume of each topic. Thirdly, the information gain method is applied to extract the high information gain characteristic words of various topics, based on which the connotation of each topic is condensed. Finally, by conducting a time series analysis of the literature, a four-quadrant matrix of topic distribution is constructed to compare the research trends of each topic within different stages. The 1186 articles in the field of text sentiment analysis from 2012 to 2022 can be divided into 12 categories. By comparing and analyzing the topic distribution matrices of the two phases of 2012 to 2016 and 2017 to 2022, it is found that the various categories of topics have obvious research development changes in different phases. The results show that: ① Among the 12 categories, online opinion analysis of social media comments represented by microblogs is one of the current hot topics. ② The integration and application of methods such as sentiment lexicon, traditional machine learning and deep learning should be enhanced. ③ Semantic disambiguation of aspect-level sentiment analysis is one of the current difficult problems this field faces. ④ Research on multimodal sentiment analysis and cross-modal sentiment analysis should be promoted.

Effects of hazard type and confidence level on hazard perception in young male drivers: an ERP study.

Hazard perception refers to a driver's ability to identify potential hazards on the road. Although studies have shown that overconfidence affects drivers' ability to perceive hazards, the neural processing of hazard perception in overconfident drivers under different hazard types has rarely been investigated. A mixed experimental design of 2 (hazard type: hazards, no hazards) × 2 (driver group: overconfident driver, control group) was used. A total of 120 images (60 with hazards and 60 without hazards) were presented to 25 overconfident drivers and 25 drivers in the control group. Reaction time, response accuracy, P200 (200-250 ms), and N2 (280-330 ms) components were measured via event-related potential (ERP) technology. Response times of overconfident drivers are slower than those of the control group regardless of hazard types. The P200 latency of overconfident drivers was longer than that of their peers in hazard situations, while the P200 latency was similar between the two groups in no-hazard situations. Although a significant interaction was found on the N2 amplitude, no significant differences were found between the two groups in both hazard and no-hazard situations. Overconfident drivers have worse hazard perception performance in hazard situations with slower reaction times and greater P200 latencies than their peers. More importantly, P200 amplitude and N2 amplitude are sensitive to hazard types, while P200 amplitude and N2 latency can discriminate between driver groups. The findings help understand the negative impact of overconfidence on young drivers and contribute to the development and training of hazard perception tests.

Effects of Sleep Deprivation and Hazard Types on the Visual Search Patterns and Hazard Response Times of Taxi Drivers.

The present study attempted to explore the effects of sleep deprivation on the visual search patterns and hazard response times of taxi drivers when they encountered different types of hazards. A two (driver groups: sleep deprivation or control) × two (hazard types: covert hazard or overt hazard) mixed experimental design was employed. A total of 60 drivers were recruited, half of whom were in the sleep-deprived group and half of whom were in the control group. A validated video-based hazard perception test that either contained covert hazards (12 video clips) or overt hazards (12 video clips) filmed from the drivers' perspective was presented to participants. Participants were instructed to click the left mouse button quickly once they detected a potentially dangerous situation that could lead to an accident. Participants' response time and eye movements relative to the hazards were recorded. The sleep-deprived group had a significantly longer response time and took a longer time to first fixate on covert hazards than the control group, while they had a shorter response time to overt hazards than the control group. The first fixation duration of sleep-deprived drivers was longer than that of the control group for overt hazards, while the duration of the first fixation of the two driver groups was similar for covert hazards. Sleep deprivation affects the visual search patterns and response times to hazards, and the adverse effects of sleep deprivation were worse in relation to covert hazards. The findings have some implications for classifying and evaluating high-risk taxi drivers whose hazard perception ability might be affected by insufficient sleep.

In vivo ocular microvasculature imaging in rabbits with 3D ultrasound localization microscopy.

Morphological and hemodynamic changes in the ocular vasculature are important signs of various ocular diseases. The evaluation of the ocular microvasculature with high resolution is valuable in comprehensive diagnoses. However, it is difficult for current optical imaging techniques to visualize the posterior segment and retrobulbar microvasculature due to the limited penetration depth of light, particularly when the refractive medium is opaque. Thus, we have developed a 3D ultrasound localization microscopy (ULM) imaging method to visualize the ocular microvasculature in rabbits with micron-scale resolution. We used a 32 × 32 matrix array transducer (center frequency: 8 MHz) with a compounding plane wave sequence and microbubbles. Block-wise singular value decomposition spatiotemporal clutter filtering and block-matching 3D denoising were implemented to extract the flowing microbubble signals at different imaging depths with high signal-to-noise ratios. The center points of microbubbles were localized and tracked in 3D space to achieve the micro-angiography. The in vivo results demonstrate the ability of 3D ULM to visualize the microvasculature of the eye in rabbits, where vessels down to 54 µm were successfully revealed. Moreover, the microvascular maps indicated the morphological abnormalities in the eye with retinal detachment. This efficient modality shows potential for use in the diagnosis of ocular diseases.

Psychometric properties of the Attitudes and Beliefs about Sleepy Driving Scale in Chinese drivers and its relationships with driving behaviours.

PURPOSE: The present study aimed to adapt the Attitudes and Beliefs about Sleepy Driving Scale (ABSDS) to a sample of Chinese drivers and to examine its reliability and validity. METHODS: Five hundred and twenty drivers aged 18 to 56 years old were asked to complete the ABSDS and a validated Chinese version of the Prosocial and Aggressive Driving Inventory. RESULTS: The results showed that the final Chinese version of the ABSDS contained 7 items with satisfactory reliability. Second, significant gender differences were found in attitude towards sleepy driving, with female drivers scoring higher than male drivers. Third, significant correlations between ABSDS score and prosocial and aggressive driving behaviours were found. More importantly, ABSDS score can significantly predict drivers' prosocial driving behaviours. Moreover, ABSDS score can significantly predict drivers' violation involvement and accident involvement. CONCLUSION: The findings supported the psychometric properties of the Chinese version of the ABSDS and suggested that it can be used to assess drivers' attitudes and beliefs about sleepy driving in China.

Adaptation and validity of the Sleep Quality Scale among Chinese drivers.

PURPOSE: Poor sleep quality is closed related with driving accidents. However, due to the lack of a valid instrument for assessing drivers' sleep quality, few studies have examined drivers' sleep quality and its associations with driving behaviours and traffic accidents in China. The aim of this paper is to revise the Sleep Quality Scale (SQS) and assess its reliability and validity in Chinese drivers. METHODS: 522 Chinese drivers aged from 18 to 56 years old agreed to complete the SQS, Daytime Sleepiness Perception Scale version 4 (DSPS-4), Self-report of Risky Driving Behavior (RD-SR) and Self-assessment of the Likelihood of Being Involved in a Risky Driving Situation (RD-SA). RESULTS: The final Chinese version of the SQS contained 23 items across four factors: difficulty in getting up, difficulty in falling asleep, sleep recovery and daytime dysfunction. Second, man scored lower on the difficulty in falling asleep factor but higher on the sleep recovery factor than women. Third, low to moderate correlations were found between the SQS factors and the DSPS-4, RD-SA and RD-SR, indicating that the validity of the revised scale was satisfactory. More importantly, daytime dysfunction factor is an effective predictor of violation involvement and accident involvement. CONCLUSION: The revised SQS has acceptable reliability and validity and can be used as a tool to measure the sleep quality of Chinese drivers.

Hepatitis B-Induced IL8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation.

Hepatitis B-associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus, leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In this study, we demonstrate that the hepatitis B virus (HBV)-encoded gene HBx induces high IL8 production through MEK-ERK signal activation, leading to enhanced endothelial permeability to facilitate tumor vascular invasion. In a vascular metastatic model using a tail vein injection in a transgenic mouse with selective expression of human CXCR1 in the endothelium, activation of the IL8-CXCR1 cascade by overexpression of IL8 in tumor cells dramatically enhanced liver metastasis. Mechanistically, IL8 selectively induced GARP-latent-TGFß in liver sinusoidal endothelial cells and subsequently provoked preferential regulatory T-cell polarization to suppress antitumor immunity. Collectively, these findings reveal a hepatitis B-associated IL8-CXCR1 signaling axis that mediates vascular invasion and local microenvironmental immune escape of HCC to induce intrahepatic metastasis, which may serve as potential therapeutic targets for HBV-associated HCC. SIGNIFICANCE: This study identifies a hepatitis B-induced IL8/CXCR1/TGFß signaling cascade that suppresses antitumor immunity and enhances metastasis in hepatocellular carcinoma, providing new potential targets for therapeutic intervention.

PEA­15 contributes to the clinicopathology and AKT­regulated cisplatin resistance in gastric cancer.

Phosphoprotein enriched in astrocytes 15 (PEA­15) plays an important role in controlling biological behaviors of cancer cells. In the present study, we demonstrated that PEA­15 was overexpressed in gastric cancer tissues and associated with tumor staging, differentiation, pathological types and the prognosis of patients. Gastric cancer cells expressed variable levels of PEA­15 and its bi­phosphorylation forms, p­PEA­15 (Ser104) and p­PEA­15 (Ser116). To gain insight into the functional role of PEA­15, we generated cells stably depleted of PEA­15 and resistant to cisplatin (CDDP) from human gastric cancer cells. PEA­15 depletion inhibited cell proliferation by reducing cyclin D1 expression through the extracellular signal­regulated kinase (ERK) pathway, resulting in cell cycle arrest at the G1 phase, and induced apoptosis by activating caspase­8. PEA­15 depletion also enhanced the inhibitory effect of CDDP that caused cell cycle arrest at the S phase and also enhanced the pro­apoptotic activity of CDDP in vitro and in animal models of tumorigenesis and therapeutic effects. PEA­15 and its phosphorylated forms were overexpressed in CDDP­resistant cells, which had higher levels of p­AKT. Specific inhibition of AKT by MK2206 reduced the expression of p­PEA­15 at the Ser116 residue, resulting in sequential downregulation of p­ERK1/2, cyclin D1 and caspase­8 activation. However, depletion of PEA­15 had little effect on AKT expression or phosphorylation, or its downstream factors including p27, glycogen synthase kinase 3ß and caspase­9, indicating that the regulatory effects between PEA­15 and AKT were unidirectional. In summary, the results indicated that PEA­15 expression was associated with clinicopathology and prognosis in gastric cancer and was regulated by AKT to participate in CDDP resistance, indicating that it may be a potential target for overcoming CDDP resistance in the treatment of gastric cancer.