The effects of distractors on brightness perception based on a spiking network.

Visual perception can be modified by the surrounding context. Particularly, experimental observations have demonstrated that visual perception and primary visual cortical responses could be modified by properties of surrounding distractors. However, the underlying mechanism remains unclear. To simulate primary visual cortical activities in this paper, we design a k-winner-take-all (k-WTA) spiking network whose responses are generated through probabilistic inference. In simulations, images with the same target and various surrounding distractors perform as stimuli. Distractors are designed with multiple varying properties, including the luminance, the sizes and the distances to the target. Simulations for each varying property are performed with other properties fixed. Each property could modify second-layer neural responses and interactions in the network. To the same target in the designed images, the modified network responses could simulate distinguishing brightness perception consistent with experimental observations. Our model provides a possible explanation of how the surrounding distractors modify primary visual cortical responses to induce various brightness perception of the given target.

The Cytidine Deaminase APOBEC3G Contributes to Cancer Mutagenesis and Clonal Evolution in Bladder Cancer.

Mutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited. Here, we showed that transgenic expression of human APOBEC3G promotes mutagenesis, genomic instability, and kataegis, leading to shorter survival in a murine bladder cancer model. Acting as mutagenic fuel, APOBEC3G increased the clonal diversity of bladder cancer, driving divergent cancer evolution. Characterization of the single-base substitution signature induced by APOBEC3G in vivo established the induction of a mutational signature distinct from those caused by APOBEC3A and APOBEC3B. Analysis of thousands of human cancers revealed the contribution of APOBEC3G to the mutational profiles of multiple cancer types, including bladder cancer. Overall, this study dissects the mutagenic impact of APOBEC3G on the bladder cancer genome, identifying that it contributes to genomic instability, tumor mutational burden, copy-number loss events, and clonal diversity. SIGNIFICANCE: APOBEC3G plays a role in cancer mutagenesis and clonal heterogeneity, which can potentially inform future therapeutic efforts that restrict tumor evolution. See related commentary by Caswell and Swanton, p. 487.

Loss of function mutations in CDKN1A are permissive for APOBEC3-induced mutagenesis in urothelial carcinoma.

Mutagenic mechanisms that shape the genomic landscape and dysfunction of DNA repair converge to promote bladder tumorigenesis. A recent study by Arnoff and El-Deiry highlights the unique interactions between CDKN1A loss of function mutations, which play a key role in cell cycle regulation, modulating DNA repair, and inducing cell apoptosis and senescence, and APOBEC3-induced mutagenesis, the predominant contributor of mutations in urothelial carcinoma.

Knowledge of Emerging and Reemerging Infectious Diseases in the Public of Guangzhou, Southern China.

OBJECTIVE: The objective of this study is to get the overall picture about the knowledge of emerging and reemerging infectious diseases in public in Guangzhou and provide a scientific basis for developing health information strategies. METHODS: We used the structured questionnaire to interview 1,000 Guangzhou residents by health enquiry hotline. Descriptive analysis was presented to evaluate the knowledge of the participants. Multiple logistic regression model was performed to determine the influence factors for knowledge of emerging and reemerging infectious diseases. RESULTS: A total of 801 individuals completed the survey. About one-third had heard of Middle East respiratory syndrome (MERS) and Zika, whereas Ebola and plague about 50%. A total of 32.08% participants had never heard of any of the four diseases. Only 2.08% knew the sexual transmission of Zika and 90.17% had no idea about the epidemic region of plague. No more than 15% knew they should check their health status after returning from the epidemic region. Education level and income were the key factors that influenced knowledge rate. CONCLUSIONS: The low-level knowledge called for the improvement in health information to the public, especially those with low level of education and income. Effective and precise health information was urged to carry out to improve the prevention for the emerging and reemerging infectious diseases.

Influencing Factors on Health Information to Improve Public Health Literacy in the Official WeChat Account of Guangzhou CDC.

Background: Social media is used as a new channel for health information. In China, the official WeChat account is becoming the most popular platform for health information dissemination, which has created a good opportunity for the Centers for Disease Control and Prevention to facilitate health information online to improve emergency public health literacy. Methods: Data were collected from the Guangzhou CDC i-Health official WeChat account between April 1, 2018 and April 30, 2019. Descriptive analysis was performed for basic information about the followers and posts of the official WeChat account. Multiple logistic regression analysis was used to analyze the association among various factors of posts on engagement of followers of the official WeChat account. Results: Among 187,033 followers, the total numbers of post views, shares, likes, add to favorites, and comments for 213 posts were 1,147,308, 8,4671, and 5,535, respectively. Engagement of followers peaked on the dissemination date and gradually declined. The main post topics were health education posts and original posts. In the multiple logistic regression model, the number of post views was found to be significantly associated with infectious disease posts (AOR: 3.20, 95% CI: 1.16-8.81), original posts (AOR: 10.20, 95% CI: 1.17-89.28), and posts with title-reflected content (AOR: 2.93, 95% CI: 1.16-8.81). Conclusion: Our findings facilitate the government to formulate better strategies and improve the effectiveness of public information dissemination.

Travel-related infection in Guangzhou, China,2009-2019.

BACKGROUND: We analyzed the epidemiological characteristics of travel-related infectious diseases in reported Guangzhou between 2009 and 2019 to provide a scientific basis for prevention and control strategies. METHOD: The infectious diseases report information system of China was mined for case reports, combined with clinical diagnosis records, and analyzed. RESULTS: Between 2009 and 2019, 1478 cases of imported infectious diseases were reported in Guangzhou. Dengue fever accounted for 46.14%of cases and malaria accounted for 45.47% of cases. The patients with imported travel-related infection cases were mainly male (75.88%), Chinese (75.57%), and aged 20-45 years (83.01%). Cases increased from May each year, peaked between August and September, and declined rapidly after October. The main source areas of import were Africa and other countries in Asia. CONCLUSIONS: Dengue fever and malaria are the main travel-related infection in Guangzhou, and are generally brought in by male Chinese workers. Intervention and health education in this population should be strengthened to prevent and control travel-related infection.

Study on Evaluation Model of Emergency Rescue Capability of Chemical Accidents Based on PCA-BP.

The emergency management of chemical accidents plays an important role in preventing the expansion of chemical accidents. In recent years, the evaluation and research of emergency management of chemical accidents has attracted the attention of many scholars. However, as an important part of emergency management, the professional rescue team of chemicals has few evaluation models for their capabilities. In this study, an emergency rescue capability assessment model based on the PCA-BP neural network is proposed. Firstly, the construction status of 11 emergency rescue teams for chemical accidents in Shanghai is analyzed, and an index system for evaluating the capabilities of emergency rescue teams for chemicals is established. Secondly, the principal component analysis (PCA) is used to perform dimension reduction and indicators' weight acquisition on the original index system to achieve an effective evaluation of the capabilities of 11 rescue teams. Finally, the indicators after dimensionality reduction are used as the input neurons of the backpropagation (BP) neural network, the characteristic data of eight rescue teams are used as the training set, and the comprehensive scores of three rescue teams are used for verifying the generalization ability of the evaluation model. The result shows that the proposed evaluation model based on the PCA-BP neural network can effectively evaluate the rescue capability of the emergency rescue teams for chemical accidents and provide a new idea for emergency rescue capability assessment.

Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling.

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.

Cross-Sectional Study on Acceptability of the Media Channels About Ebola Virus Disease in Guangzhou, China.

OBJECTIVES: The purpose of this study was to explore the relationship between the information seeking about Ebola virus disease (EVD) and media channels, then to provide theory evidence for working out the health education transmission strategy in similar public health emergency events. MATERIALS AND METHODS: We used a cross-sectional survey model, data were collected through questionnaire over telephone calls, and R × c chi-square test was used to identify factors associated with knowledge and media channels for choosing to get the information about EVD prevention and control. RESULTS: Most of the respondents said they heard of EVD (84.9%). A total of 82.1% of respondents knew that Ebola virus outbreak occurred in Africa in 2014. Less than half of the respondents knew "EVD can be transmitted through contact with the body, or bodily fluids of an infected person directly" (43.8%). More than half of respondents preferred getting EVD-related information through television, making it the most favored method (60.9%). Information through newspaper was in second place (15.6%) and community propaganda was the third (11.3%). The top three modes of demanding to receive information about EVD mentioned by the respondents were television (55.0%), networking (18.8%), and newspaper (12.1%). CONCLUSIONS: Television should be used to disseminate relevant accurate health information to the public. The public health organization should strengthen existing partnerships with news media and social media.

High mucin 5AC expression predicts adverse postoperative recurrence and survival of patients with clear-cell renal cell carcinoma.

BACKGROUND: Mucin 5AC (MUC5AC), as a member of secreted/gel-forming mucin family, was frequently found to be abnormally expressed in inflammation or malignant diseases. However, the clinic pathologic features and prognostic values of MUC5AC in clear-cell renal cell carcinoma (ccRCC) have not been reported up to now. METHODS: MUC5AC expression was analyzed by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves, Univariate and Multivariate Cox analysis and newly-established nomogram model were performed to evaluate the prognostic value. RESULTS: MUC5AC expression was firstly found to be up-regulated in patients with ccRCC, positively associated with tumor size, pN stage, lymphovascular invasion, Fuhrman grade, rahbdoid differentiation, sarcomatoid features, tumor necrosis, ECOG-PS and recurrence. Furthermore, MUC5AC expression might be contributed to risk stratification of ccRCC patients with TNM stage III+IV or Fuhrman grade 3 or 4 for overall survival (OS) and recurrence-free survival (RFS) analysis, and it was demonstrated to be negatively correlated with OS and RFS of ccRCC patients. What's more, MUC5AC was identified as a potential independent adverse prognostic factor; prediction accuracy of MUC5AC-based new nomogram model was drastically improved for OS and RFS of ccRCC patients. CONCLUSION: MUC5AC is a promising independent adverse prognostic factor for ccRCC patients, it maybe conducive to postoperative risk stratification and guide treatment in the future.

Galectin-9 as a prognostic and predictive biomarker in bladder urothelial carcinoma.

PURPOSE: Galectin-9, a member of the "tandem repeat" type galectins performing as animal lectins with an affinity for ß-galactosides, has been well documented to exert crucial functions in immunomodulation, survival, and growth of various tumors. This study aims to reveal the clinical significance of galectin-9 in urothelial carcinoma of the bladder (UCB) postoperatively. MATERIALS AND METHODS: We retrospectively included 202 patients with UCB who underwent radical cystectomy at a single institute from 2002 to 2014. Galectin-9 expression was assessed by immunohistochemistry on tissue microarrays. The Kaplan-Meier method was conducted to plot survival curves. Prognostic nomograms were constructed via integrating all the independent indicators from multivariate Cox analysis for recurrence-free survival (RFS) and cancer-specific survival (CSS). In addition, we evaluate whether patients with increased or decreased galectin-9 expression might benefit from adjuvant chemotherapy. RESULTS: Low galectin-9 expression was significantly correlated with lymphovascular invasion (P = 0.002), early recurrence (P = 0.010), and short CSS (P = 0.002). Furthermore, multivariate analysis identified galectin-9 expression as a potential independent indicator for RFS (hazard ratio = 0.62; 95% CI: 0.40-0.95; P = 0.030) and CSS (hazard ratio = 0.46; 95% CI: 0.26-0.81; P = 0.008). Moreover, the benefit associated with adjuvant chemotherapy was superior among galectin-9 low patients than among galectin-9 high patients (P = 0.014). CONCLUSIONS: Expression of galectin-9 is an independent prognostic factor for RFS and CSS in patients with UCB. Evaluation of galectin-9 expression may predict the benefit from adjuvant chemotherapy.

Loss of N-Acetylgalactosaminyltransferase-4 Orchestrates Oncogenic MicroRNA-9 in Hepatocellular Carcinoma.

Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients.

Prognostic significance of ubiquinol-cytochrome c reductase hinge protein expression in patients with clear cell renal cell carcinoma.

Ubiquinol-cytochrome c reductase hinge protein (UQCRH), as a connecter between cytochrome c1 with cytochrome c in complex III of respiratory chain, is top-ranked hypermethylated gene in clear cell renal cell carcinoma (ccRCC). This study aims to evaluate the impact of UQCRH on recurrence and survival of 424 ccRCC patients enrolled retrospectively from a single institution after surgical resection using immunohistochemistry method. UQCRH was specifically downregulated in ccRCC, compared with papillary and chromophobe RCC. Moreover, patients with low UQCRH were prone to possess high T stage and TNM stage and associated with poor survival and early recurrence. UQCRH remained an independent favorable prognosticator for OS (Hazard rate [HR]: 0.510, 95% CI: 0.328-0.795, p=0.003) and RFS (HR: 0.506, 95% CI: 0.334-0.767, p=0.001) adjusting with other well-established factors using backward Cox model. Furthermore, in stratified subgroups, patients with low UQCRH had an increased risk of recurrence (HR: 0.452, 95% CI: 0.261-0.783, p=0.005) and mortality (HR: 0.386, 95% CI: 0.205-0.726, p=0.003) in subgroup of early TNM stage. Taken together, UQCRH is a potential independent favorable prognostic factor for recurrence and survival of patients with ccRCC after nephrectomy.

Elevated expression of IFN-inducible CXCR3 ligands predicts poor prognosis in patients with non-metastatic clear-cell renal cell carcinoma.

IFN-inducible CXCR3 ligands (ICL), namely CXCL9, CXCL10 and CXCL11, exhibit pleiotropic roles in orchestrating immunity and angiogenesis. However, the prognosis value of them in renal cell carcinoma (RCC) was still obscure. Thus, we retrospectively used immunohistochemistry approach to evaluate the impact of these ligands on recurrence and survival of non-metastatic clear cell RCC (ccRCC) patients after nephrectomy. We systemically built a prespecified ICL score based on these ligands, and found specimens with high ICL score were prone to possess high Fuhrman grade, necrosis, and high-risk level of SSIGN. Moreover, ICL score stratified patients into different risk subgroups, and remained an independent adverse prognosticator for overall survival (OS) and recurrence-free survival (RFS). Meanwhile, in TCGA database, the increasing ICL mRNA predicted poor survival and early recurrence. Furthermore, after adding ICL score into SSIGN, the C-index for OS and RFS increased from 0.705 to 0.746 and 0.712 to 0.765, respectively. In conclusion, the ICL score based on expression of CXCL9, CXCL10 and CXCL11 stratified non-metastatic ccRCC patients into different risk subgroups of recurrence and death, which might benefit preoperative risk stratification and guide immune therapy in the future.

Increased expression of interleukin-8 is an independent indicator of poor prognosis in clear-cell renal cell carcinoma.

On the basis of aberrant interleukin-8 (IL-8) expression, a crucial angiogenesis factor and potential therapeutic target, in clear-cell renal cell carcinoma (ccRCC), this study aims to assess the prognostic significance of IL-8 in ccRCC. This retrospective study enrolled 271 patients who underwent nephrectomy for ccRCC in a single institution. The associations of IL-8 expression with clinical and pathological features were assessed using chi-squared tests. The impact on cancer-specific survival (CSS) and relapse-free survival (RFS) was analyzed using univariable and multivariable Cox regression models. The area under the receiver operating characteristic (ROC) curve (AUC) was used as an index of prognostic performance. Intratumoral IL-8 was found to be significantly elevated in ccRCC tissues compared with peritumor tissue and be predominately localized in the cytoplasm. Moreover, high IL-8 expression was positively correlated with Fuhrman grade (P < 0.001). Multivariate Cox regression analysis identified IL-8 as an independent adverse prognostic factor of CSS (P < 0.001) and RFS (P < 0.001), which could be incorporated into the traditional TNM staging system to improve the prognostic value for CSS and RFS in ccRCC patients. The predictive accuracy of traditional TNM stage model was significantly improved when IL-8 expression was added. Increased expression of IL-8 is a potential independent adverse prognostic biomarker for CSS and RFS in patients with ccRCC after nephrectomy.

Decreased Expression of SETD2 Predicts Unfavorable Prognosis in Patients With Nonmetastatic Clear-Cell Renal Cell Carcinoma.

DNA sequencing revealed that mutations in SETD2 occur in 3% to 12% of clear-cell renal cell carcinoma (ccRCC) cases and are associated with poor clinical outcome. In this study, we used an immunohistochemistry (IHC) assay to evaluate the impact of SETD2 loss, with expression of H3K36me3, a nonredundantly histone modification by SETD2, on recurrence and survival of nonmetastatic ccRCC patients after nephrectomy.SETD2 and H3K36me3 were assessed in 192 nonmetastatic ccRCC patients enrolled retrospectively from a single institution. Kaplan-Meier and Cox regression analysis were used to associate prespecified SETD2/H3K36me3 score with overall survival (OS) and recurrence-free survival (RFS). And a nomogram was constructed to predict OS at 10 years.Patients with low expression of SETD2 were prone to possess large tumor size and advanced pT stage. And low H3K36me3 expression was associated with larger tumor size. A prespecified combined score based on SETD2 and H3K36me3 expression remained an independent prognosticator for OS and RFS, which was associated with tumor size, pT stage, and sarcomatoid. Furthermore, using prespecified SETD2/H3K36me3 score could stratify nonmetastatic ccRCC patients into different risk subgroups, especially in patients dichotomized by pT stage and Fuhrman grade, respectively. Finally, the C-index for predicting OS increased from 0.727 to 0.747, after adding SETD2/H3K36me3 score to pT stage and Fuhrman grade.The combined score based on expression of SETD2 and H3K36me3 using IHC could predict poor clinical outcomes in nonmetastatic ccRCC patients, and it may benefit preoperative risk stratification and guide treatment planning in the future.

Tumor Suppressive Function of p21-activated Kinase 6 in Hepatocellular Carcinoma.

Our previous studies identified the oncogenic role of p21-activated kinase 1 (PAK1) in hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Contrarily, PAK6 was found to predict a favorable prognosis in RCC patients. Nevertheless, the ambiguous tumor suppressive function of PAK6 in hepatocarcinogenesis remains obscure. Herein, decreased PAK6 expression was found to be associated with tumor node metastasis stage progression and unfavorable overall survival in HCC patients. Additionally, overexpression and silence of PAK6 experiments showed that PAK6 inhibited xenografted tumor growth in vivo, and restricted cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis and anoikis in vitro. Moreover, overexpression of kinase dead and nuclear localization signal deletion mutants of PAK6 experiments indicated the tumor suppressive function of PAK6 was partially dependent on its kinase activity and nuclear translocation. Furthermore, gain or loss of function in polycomb repressive complex 2 (PRC2) components, including EZH2, SUZ12, and EED, elucidated epigenetic control of H3K27me3-arbitrated PAK6 down-regulation in hepatoma cells. More importantly, negative correlation between PAK6 and EZH2 expression was observed in hepatoma tissues from HCC patients. These data identified the tumor suppressive role and potential underlying mechanism of PAK6 in hepatocarcinogenesis.

EZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma.

The CXC chemokine receptor 4 (CXCR4) exerts a variety of functions at different steps of hepatocellular carcinoma (HCC) progression. The molecular mechanisms and therapeutic value of CXCR4 in the development of HCC remain undefined. Here we show that aberrant CXCR4 overexpression is associated with poor prognosis and aggressive characteristics of HCC. Suppression of CXCR4 activity via CXCR4 knockdown, AMD3100 or neutralizing antibody administration inhibits hepatoma cell tumorigenesis in vitro and in vivo. CXCR4 overexpression displays the opposite effects. Using Mir library screening we identify miR-622 as a regulator of CXCR4. Further studies show that miR-622 directly target the 3' untranslated region of CXCR4 and is transcriptionally repressed by EZH2-induced H3K27 trimethylation and promoter methylation. EZH2/miR-622 promotes tumorigenesis through CXCR4. EZH2-mediated loss of miR-622 is found to correlate with CXCR4 overexpression and unfavourable prognosis in HCC patients. This study establishes EZH2/miR-622/CXCR4 as a potential adverse prognostic factor and therapeutic target for HCC patients.

Prognostic significance of ß1,6-N-acetylglucosaminyltransferase V expression in patients with hepatocellular carcinoma.

OBJECTIVE: Alterations to the N-glycans in glycoproteins have been suggested to play important roles in the proliferation, differentiation, invasion and metastasis of hepatocellular carcinoma (HCC). This study aims to evaluate the potential prognostic value of ß1,6-N-acetylglucosaminyltransferase V (Mgat5) in hepatocellular carcinoma patients after surgical resection. METHODS: We retrospectively enrolled 300 patients (156 in the training cohort and 144 in the validation cohort) with hepatocellular carcinoma undergoing hepatectomy at a single institution. Mgat5 intensities were assessed by immunohistochemistry in the specimens of patients. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. RESULTS: Intratumoral Mgat5 expression was significantly higher than non-tumoral tissues (P < 0.001). In both cohorts, elevated Mgat5 expression in tumor tissues positively correlated with vascular invasion and advanced tumor-node-metastasis stage. High Mgat5 expression indicated poor survival (P < 0.001 in the training cohort and P < 0.001 in the validation cohort) and recurrence (P < 0.001 in both cohorts, respectively) in patients with hepatocellular carcinoma, particularly with early-stage disease. Mgat5 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of tumor-node-metastasis and Barcelona Clinic Liver Cancer prognostic models was improved when Mgat5 expression was added. CONCLUSION: Mgat5 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with hepatocellular carcinoma after hepatectomy.