mSigSDK - private, at scale, computation of mutation signatures.

In our previous work, we demonstrated that it is feasible to perform analysis on mutation signature data without the need for downloads or installations and analyze individual patient data at scale without compromising privacy. Building on this foundation, we developed an in-browser Software Development Kit (a JavaScript SDK), mSigSDK, to facilitate the orchestration of distributed data processing workflows and graphic visualization of mutational signature analysis results. We strictly adhered to modern web computing standards, particularly the modularization standards set by the ECMAScript ES6 framework (JavaScript modules). Our approach allows for the computation to be entirely performed by secure delegation to the computational resources of the user's own machine (in-browser), without any downloads or installations. The mSigSDK was developed primarily as a companion library to the mSig Portal resource of the National Cancer Institute Division of Cancer Epidemiology and Genetics (NIH/NCI/DCEG), with a focus on FAIR extensibility as components of other researchers' own data science constructs. Anticipated extensions include the programmatic operation of other mutation signature API ecosystems such as SIGNAL and COSMIC, advancing towards a data commons for mutational signature research (Grossman et al., 2016).

A prospective comparison of three ultrasound-based techniques in quantitative diagnosis of hepatic steatosis in NAFLD.

PURPOSE: To investigate the correlation between different ultrasound attenuation-based techniques and to compare their diagnostic performances using proton magnetic resonance spectroscopy (1H-MRS) as a reference standard. METHODS: Participants who had clinical suspicion of nonalcoholic fatty liver disease (NAFLD) were prospectively recruited. Each subject had ultrasound with attenuation imaging (ATI) or quantitative ultrasound including tissue attenuation imaging (TAI) and tissue scatter-distribution imaging (TSI), and controlled-attenuation parameter (CAP) and 1H-MRS if available. The technical success rates, intra-observer repeatabilities of attenuation and backscattering coefficient were evaluated. ATI, TAI and CAP were three attenuation-based techniques. Spearman coefficient was used to test correlations among them and 1H-MRS. In addition, the diagnostic performances of these parameters for detecting ≥ 5% or 10% hepatic steatosis were evaluated. RESULTS: 130 participants had ultrasound scanning. Among them, 67 had CAP and 48 had 1H-MRS. The technical success rates were all 100%. The intra-observer repeatabilities of them were also excellent (ICCs > 0.90) and AC-ATI correlated well with AC-TAI (r = 0.752). AC-ATI, AC-TAI showed moderate correlation with CAP, (rATI = 0.623, 95% CI 0.446-0.752, P < 0.001; rTAI = 0.573, 95% CI 0.377-0.720, P < 0.001). For correlation with 1H-MRS, ATI and TAI performed better than CAP(rATI = 0.587; rTAI = 0.712; r CAP = 0.485). The AUCs of ATI, TAI, TSI and CAP for detecting ≥ 5% hepatic steatosis were 0.883, 0.862, 0.870 and 0.868, respectively. The AUC improved to 0.907 when TAI and TSI were combined (P < 0.05). When detecting ≥ 10% hepatic steatosis, the AUCs were 0.855, 0.702, 0.822 and 0.838, respectively. CONCLUSION: Different ultrasound attenuation-based techniques were well correlated and exhibited good diagnostic performances in quantitative diagnosis of hepatic steatosis, however, the threshold values were different. Combinations of multiple parameters may improve the diagnostic performance in detecting hepatic steatosis. TRIAL REGISTRATION: The study has been registered online ( https://www.chictr.org.cn ; unique identifier: ChiCTR2300069459).

Ultrasound findings of hepatic epithelioid hemangioendothelioma: comparison with other malignant hepatic tumors.

PURPOSE: To investigate and compare the ultrasonic features of hepatic epithelioid hemangioendothelioma (HEHE) and other common hepatic malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatic metastatic tumor (HMT). METHODS: A total of 37 patients with pathologically proven HEHE, 37 HCC cases, 37 ICC cases, and 37 HMT cases were enrolled from single hospital. The clinical characteristics and ultrasonic features of all cases were summarized and statistically analyzed. RESULTS: There were significant differences in sex and age between the HEHE group and other three groups (P < 0.001). The probability of HEHE infection with hepatitis B virus was lower than that of HCC and ICC groups (P < 0.05). The probability of elevated serum tumor markers in HEHE was significantly lower than that in the other three groups (P < 0.05). On conventional ultrasound (CUS), the probability of multiple lesions in HEHE was significantly higher than that in the other three groups (P < 0.05). On contrast-enhanced ultrasound (CEUS), the time to wash out in HEHE was significantly shorter than that of the other three groups (P < 0.001). The proportion of synchronous or slow enhancement in HEHE was significantly higher than that of the other three groups (P < 0.001). The proportion of HEHE with iso- or hypo-enhancement was significantly higher than in HCC and HMT groups (P < 0.05). CONCLUSION: HEHE mainly performed multiple hypoechoic lesions on CUS and displayed greater odds of synchronous enhancement in arterial phase, iso- or hypo-enhancement in peak time and wash out more quickly on CEUS, which allowed for differentiation from other common malignant tumors.

Contrast-Enhanced Imaging Features and Clinicopathological Investigation of Steatohepatitic Hepatocellular Carcinoma.

Steatohepatitic hepatocellular carcinoma (SH-HCC) is a distinctive histologic variant of HCC for the presence of steatohepatitis. This study intended to evaluate the contrast-enhanced imaging features and clinicopathological characteristics of 26 SH-HCCs in comparison with 26 age-and-sex-matched non-SH-HCCs. The frequency of obesity (34.6%, p = 0.048) and type 2 diabetes mellitus (23.1%, p = 0.042) were significantly higher in SH-HCC patients. As seen via B-mode ultrasound (BMUS), SH-HCCs were predominantly hyperechoic (65.4%, p = 0.002) lesions, while non-SH-HCCs were mainly hypo-echoic. As seen via contrast-enhanced ultrasound (CEUS), 96.2% of SH-HCCs exhibited hyperenhancement in the arterial phase. During the portal venous and late phase, 88.5% of SH-HCCs showed late and mild washout. Consequently, most SH-HCCs and all non-SH-HCCs were categorized as LR-4 or LR-5. As seen via magnetic resonance imaging (MRI), a signal drop in the T1WI opposed-phase was observed in 84.6% of SH-HCCs (p = 0.000). Notably, diffuse fat in mass was detected in 57.7% (15/26) SH-HCCs (p < 0.001). As seen via contrast-enhanced MRI (CEMRI), most of the SH-HCCs and non-SH-HCCs exhibited heterogeneous hyperenhancement in the arterial phase (80.8% versus 69.2%, p = 0.337). During the delayed phase, 76.9% SH-HCCs and 88.5% non-SH-HCCs exhibited hypo-enhancement. Histopathologically, the rate of microvascular invasion (MVI) was significantly lower in SH-HCCs than non-SH-HCCs (42.3% versus 73.1%, p = 0.025). The frequency of hepatic steatosis >5% in non-tumoral liver parenchyma of SH-HCCs was significantly higher than in non-SH-HCCs (88.5% versus 26.9%, p = 0.000). Additionally, the fibrotic stages of S0, S1 and S2 in SH-HCCs were significantly higher than in non-SH-HCCs (p = 0.044). During follow-up, although the PFS of SH-HCC patients was significantly longer than non-SH-HCC patients (p = 0.046), for the overall survival rate of SH-HCC and non-SH-HCC patients there was no significant difference (p = 0.162). In conclusion, the frequency of metabolism-related diseases in SH-HCC patients was significantly higher than in non-SH-HCC patients. The imaging features of SH-HCCs combined the fatty change and typical enhancement performance of standard HCC as seen via CEUS/CEMRI.

Intrahepatic splenosis: Contrast enhanced ultrasound and magnetic resonance imaging findings.

OBJECTIVE: To evaluate the contrast enhanced ultrasound (CEUS) and contrast enhanced magnetic resonance imaging (CEMRI) features of intrahepatic splenosis (IHS). METHODS & MATERIALS: Five patients (three males and two females, median age, 44 years; range,32-73 years) with seven IHSs were retrieved from the database of our hospital from March 2012 to October 2021. All IHSs were confirmed histologically by surgery. The CEUS and CEMRI characteristics of individual lesion were fully analyzed. RESULTS: All IHS patients were asymptomatic and four out of five patients had history of splenectomy. On CEUS, all IHSs were hyperenhancement in arterial phase. 71.4% (5/7) of IHSs manifested overall filling within few seconds, the other two lesions showed centripetal filling. Subcapsular vascular hyperenhancement and feeding artery was seen in 28.6% (2/7) and 42.9% (3/7) of IHSs, respectively. During portal venous phase, IHSs presented hyperenhancement (2/7) or isoenhancement (5/7). Moreover, rim-like hypoenhanced area was uniquely observed surrounding 85.7% (6/7) of IHSs. In late phase, seven IHSs remained continuous hyper- or isoenhancement. On CEMRI, five IHSs showed mosaic hyperintense in early arterial phase, the other two lesions showed homogeneous hyperintense. In portal venous phase, all IHSs revealed continuous hyper- (71.4%, 5/7) or iso-intense (28.6%, 2/7). During late phase, one IHS (14.3%, 1/7) became hypointense, the other lesions remained hyper- or isointense. CONCLUSION: Diagnosis of IHS can be based on typical CEUS and CEMRI features in patients with history of splenectomy.

GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55-74 at enrollment in 1993-2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

PLCOjs, a FAIR GWAS web SDK for the NCI Prostate, Lung, Colorectal and Ovarian Cancer Genetic Atlas project.

MOTIVATION: The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110 000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here. RESULTS: The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services. AVAILABILITY AND IMPLEMENTATION: code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco.

Identification and fine-mapping of Xo2, a novel rice bacterial leaf streak resistance gene.

KEY MESSAGE: A novel rice resistance gene, Xo2, influencing pathogenesis of the bacterial leaf streak disease, has been identified, and candidate genes for Xo2 in the fine mapping region have been shown to be involved in bacterial leaf streak resistance. Rice (Oryza sativa) bacterial leaf streak, caused by Xanthomonas oryzae pv. oryzicola (Xoc), is one of the most serious rice bacterial diseases. The deployment of host resistance genes is an effective approach for controlling this disease. The cultivar BHADOIA 303 (X455) from Bangladesh is resistant to most of Chinese Xoc races. To identify and map the resistance gene(s) involved in Xoc resistance, we examined the association between phenotypic and genotypic variations in two F2 populations derived from crosses between X455/Jingang 30 and X455/Wushansimiao. The segregation ratios of the F2 progeny were consistent with the action of a single dominant resistance gene, which was designated as Xo2. Based on rice SNP chip (GSR40K) assays of X455, Jingang 30, and resistant and susceptible pools thereof, we mapped Xo2 to the region from 10 Mb to 12.5 Mb on chromosome 2. The target gene was further finely mapped between the markers RM12941 and D6-1 within an approximately 110-kb region. The de novo sequencing and gene annotation of X455 and Jingang 30 revealed nineteen predicted genes within the target region. RNA-seq and expression analysis showed that four candidate genes, including Osa002T0115800, encoding an NLR resistance protein, were distinctly upregulated. Differential sequence and synteny analysis between X455 and Jingang 30 suggested that Osa002T0115800 is likely the functional Xo2 gene. This study lays a foundation for marker-assisted selection resistance breeding against rice bacterial leaf streak and the further cloning of Xo2.

Ultrasound-Guided Coarse Needle Biopsy Diagnosed Isolated Hepatic Malignant Melanoma with Undetermined Origin in TB Patient: A Case Report.

Isolated hepatic malignant melanoma with undetermined origin is relatively rare and the imaging findings vary significantly in published studies. In this report, we described an elderly male patient with pulmonary tuberculosis who was diagnosed with isolated hepatic malignant melanoma with undetermined origin by ultrasound-guided percutaneous coarse needle biopsy (US-CNB). The hepatic melanoma was detected accidentally on chest CT. On contrast-enhanced ultrasound (CEUS), it presented an enhancement pattern of fast washin and slow washout. However, on magnetic resonance imaging (CEMRI), it showed non-rim hyperenhancement in the arterial phase but hypointensity in the late phase, mimicking hepatocellular carcinoma. With inconsistent results, the patient underwent fluorine-18-fluro-2-deoxy-D-glucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). The mass showed mild 18F-FDG uptake with SUVmax of 4.7, and hypermetabolic nodules were observed in the lung, chest wall, thoracic vertebra, and pelvis. Due to the advanced stage of the tumor, US-CNB was performed to acquire a pathological diagnosis. The immunohistochemical staining suggested malignant melanoma. Of note, no primary tumor was revealed. Finally, the patient refused systemic therapy and died from tumor progression seven months later. Hence, CEUS and CEMRI is fundamental in the diagnosis of hepatic melanoma, and PET-CT is helpful in clinical staging. For controversial results, US-CNB is required to establish the pathological diagnosis.

COMETS Analytics: An Online Tool for Analyzing and Meta-Analyzing Metabolomics Data in Large Research Consortia.

Consortium-based research is crucial for producing reliable, high-quality findings, but existing tools for consortium studies have important drawbacks with respect to data protection, ease of deployment, and analytical rigor. To address these concerns, we developed COnsortium of METabolomics Studies (COMETS) Analytics to support and streamline consortium-based analyses of metabolomics and other -omics data. The application requires no specialized expertise and can be run locally to guarantee data protection or through a Web-based server for convenience and speed. Unlike other Web-based tools, COMETS Analytics enables standardized analyses to be run across all cohorts, using an algorithmic, reproducible approach to diagnose, document, and fix model issues. This eliminates the time-consuming and potentially error-prone step of manually customizing models by cohort, helping to accelerate consortium-based projects and enhancing analytical reproducibility. We demonstrated that the application scales well by performing 2 data analyses in 45 cohort studies that together comprised measurements of 4,647 metabolites in up to 134,742 participants. COMETS Analytics performed well in this test, as judged by the minimal errors that analysts had in preparing data inputs and the successful execution of all models attempted. As metabolomics gathers momentum among biomedical and epidemiologic researchers, COMETS Analytics may be a useful tool for facilitating large-scale consortium-based research.

Differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced ultrasound: A systematic review and meta-analysis.

AIM: To explore the diagnostic ability of contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies reporting the diagnostic accuracy of CEUS in differentiating ICC from HCC. The diagnostic ability of CEUS was assessed based on the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) with 95% confidence intervals (CIs). The methodologic quality was assessed by the QUADAS-2 tool. Subgroup analyses, meta-regression and investigation of publication bias were performed to identify the source of heterogeneity. RESULTS: A total of eight studies were included, consisting of 1,116 patients with HCC and 529 with ICC. The general diagnostic performance of CEUS in distinguishing ICC and HCC were as follows: pooled sensitivity, 0.92 (95% CI: 0.84-0.96); pooled specificity, 0.87 (95% CI: 0.79-0.92); pooled PLR, 7.1 (95% CI: 4.1-12.0); pooled NLR, 0.09 (95% CI: 0.05-0.19); pooled DOR, 76 (95% CI: 26-220) and AUC, 0.95 (95% CI: 0.93-0.97). Different liver background may be a potential factor that influenced the diagnostic accuracy of CEUS according to the subgroup analysis, with the pooled DOR of 89.67 in the mixed liver background group and 46.87 in the cirrhosis group, respectively. Six informative CEUS features that may help differentiate HCC from ICC were extracted. The three CEUS features favoring HCC were arterial phase hyperenhancement (APHE), mild washout and late washout (>60s); the three CEUS favoring ICC were arterial rim enhancement, marked washout and early washout (<60s). No potential publication bias was observed. CONCLUSION: CEUS showed great diagnostic ability in differentiating ICC from HCC, which may be promising for noninvasive evaluation of these diseases.

High-Frame Rate Vector Flow Imaging Technique: Initial Application in Evaluating the Hemodynamic Changes of Carotid Stenosis Caused by Atherosclerosis.

Objective: To investigate the value of high-frame rate vector flow imaging technique (V flow) in evaluating the hemodynamic changes of carotid stenosis caused by atherosclerotic plaques. Methods and Materials: In this prospective study, patients with stenosis rate (diameter) ≥30% caused by carotid atherosclerotic plaques were included. Degrees of carotid stenosis were graded according to North American Symptomatic Carotid Endarterectomy Trial criteria: moderate (30-69%) or severe (70-99%). Mindray Resona 7s ultrasound machine with a linear array transducer (3-11 MHz) was used for ultrasound examinations. The mean WSS value of carotid arteries was measured at the proximal, narrowest region and distal of carotid stenosis. The mean WSS values were correlated with peak systolic velocity (PSV) measured by color Doppler flow imaging and stenosis degree detected by digital subtraction angiography (DSA). The vector arrows and flow streamline detected by V flow dynamic imaging were analyzed. Imaging findings of DSA in carotid arteries were used as the gold standard. Results: Finally, 51 patients were included. V flow measurements were performed successfully in 17 patients (100%) with moderate-grade stenosis and in 30 patients (88.2%) with severe-grade stenosis. Dynamic V flow imaging showed yellow or red vectors at the stenotic segment, indicating fast speed blood flow (up to 260.92 cm/s). Changes of streamlines were detected in the stenotic segment. The mean WSS value measured at the narrowest region of the carotid artery had a moderately positive correlation with stenosis degree (r = 0.58, P < 0.05) and PSV value (r = 0.54, P < 0.05), respectively. Significant difference was detected in mean WSS value at the narrowest region of the carotid artery between severe carotid stenosis (1.47 ± 0.97 Pa) and moderate carotid stenosis (0.96 ± 0.44 Pa) (P < 0.05). Conclusion: The hemodynamic changes detected by V flow of the carotid stenosis might be a potential non-invasive imaging tool for assessing the degree of carotid stenosis.

Early evaluation of treatment response to transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The role of dynamic three-dimensional contrast-enhanced ultrasound.

BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1-3 days (T1) after treatment. Tumor microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients.

Dynamics of the Rice Blast Fungal Population in the Field After Deployment of an Improved Rice Variety Containing Known Resistance Genes.

Rice blast, caused by the fungus Magnaporthe oryzae, is one of the most destructive diseases of rice worldwide. Management through the deployment of host resistance genes would be facilitated by understanding the dynamics of the pathogen's population in the field. Here, to investigate the mechanism underlying the breakdown of disease resistance, we conducted a six-year field experiment to monitor the evolution of M. oryzae populations in Qujiang from Guangdong. The new variety of Xin-Yin-Zhan (XYZ) carrying R genes Pi50 and Pib was developed using the susceptible elite variety, Ma-Ba-Yin-Zhan (MBYZ), as the recurrent line. Field trials of disease resistance assessment revealed that the disease indices of XYZ in 2012, 2013, 2016, and 2017 were 0.19, 0.39, 0.70, and 0.90, respectively, indicating that XYZ displayed a very rapid increase of disease severity in the field. To investigate the mechanism underlying the quick erosion of resistance of XYZ, we collected isolates from both XYZ and MBYZ for pathogenicity testing against six different isogenic lines. The isolates collected from XYZ showed a similar virulence spectrum across four different years whereas those from MBYZ showed increasing virulence to the Pi50 and Pib isogenic lines from 2012 to 2017. Molecular analysis of AvrPib in the isolates from MBYZ identified four different AvrPib haplotypes, i.e., AvrPib-AP1-1, AvrPib-AP1-2, avrPib-AP2, and avrPib-AP3, verified by sequencing. AvrPib-AP1-1 and AvrPib-AP1-2 are avirulent to Pib whereas avrPib-AP2 and avrPib-AP3 are virulent. Insertions of a Pot3 and an Mg-SINE were identified in avrPib-AP2 and avrPib-AP3, respectively. Two major lineages based on rep-PCR analysis were further deduced in the field population, implying that the field population is composed of genetically related isolates. Our data suggest that clonal propagation and quick dominance of virulent isolates against the previously resistant variety could be the major genetic events contributing to the loss of varietal resistance against rice blast in the field.

Analysis of contrast-enhanced ultrasound features of hepatocellular adenoma according to different pathological molecular classifications.

OBJECTIVE: To explore the specific contrast-enhanced ultrasound (CEUS) features of hepatocellular adenomas (HCA) according to their pathological molecular classifications. METHODS & MATERIALS: In this retrospective study, fifty-three histopathologically proved HCA lesions (mean size, 39.7±24.9 mm) were included. Final histopathological diagnosis of HCA lesions were identified by surgical resection (n = 51) or biopsy (n = 2) specimens. CEUS imaging features were compared among four subgroups according to World Health Organization (WHO) 2019 pathological molecular classifications standards. Analysis of variance (ANOVA) were used for statistical analysis of continuous variables. Fisher's exact test were used for categorical variables. The sensitivity (SE), specificity (SP), and accuracy of CEUS feature in diagnosis of each HCA subtype were calculated and compared. RESULTS: Final histopathological diagnosis included HNF-1α inactivated HCAs (H-HCA, n = 12), ß-catenin activated HCAs (B-HCA, n = 8), inflammatory HCAs (I-HCA, n = 31), and unclassified HCAs (U-HCA, n = 2). During arterial phase of CEUS, all HCAs were hyper-enhanced, 66.6% (8/12) of H-HCAs and 50% (4/8) of B-HCAs displayed complete hyperenhancement, whereas 58.0% (18/31) of I-HCAs showed centripetal filling hyperenhancement pattern (P = 0.016). Hyper-enhanced subcapsular arteries could be detected in 64.5% (20/31) I-HCAs during early arterial phase. During portal venous and late phase, sustained hyper- or iso-enhancement were observed in 91.7% (11/12) of H-HCAs, while most of I-HCAs (61.3%, 19/31) and B-HCAs (7/8, 87.5%) were hypo-enhanced (P = 0.000). Central unenhanced areas were most commonly observed in I-HCAs (29.0%, 9/31) (P = 0.034). CONCLUSION: Depending on its unique imaging features including enhancement filling pattern, hyper-enhanced subcapsular artery and presence of washout, CEUS might provide helpful diagnostic information for preoperative prediction of various HCA molecular subtypes.

V Flow technology in measurement of wall shear stress of common carotid arteries in healthy adults: Feasibility and normal values.

OBJECTIVE: To evaluate the feasibility of vector flow imaging technique (V Flow) in measurement of wall shear stress (WSS) of common carotid arteries (CCA) in healthy adults and to provide the normal WSS values assessed by V Flow. METHODS & MATERIALS: This prospective study was approved by the Ethics Committee of our University. Eighty healthy adult volunteers were included (mean age 43.3 y, 47 females, 33 males). The volunteers were classified into three groups according to their age: group I (age 20 - 39 y), group II (age 40 - 59 y) and group III (age 60 - 80 y). Mindray Resona 8 ultrasound machine and a linear array transducer (3-9 MHz) was used, equipped with the updated V Flow function. Common carotid arteries of both sides were evaluated in three segments (initial segment, middle segment and near bifurcation segment). The WSS values of CCA were measured by two independent radiologists. The intraclass correlation coefficient (ICC) of observer reliability in WSS measurement was calculated. Inter-observer reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). RESULTS: V Flow measurements were performed successfully in 79 volunteers (98.8 %, 79/80). The mean value of WSS in right CCA was (0.66±0.24) Pa, in left CCA was (0.66±0.18) Pa (P > 0.05). Mean WSS value had a moderately negative correlation with age group (P < 0.05). The mean WSS value of group I(mean±SD, 0.75±0.25 Pa) is larger than group II (mean±SD, 0.62±0.13 Pa) and group III (mean±SD, 0.49±0.11 Pa) (P < 0.05). The ICC of observer reliability of group I, II and III was 0.96 (95% confidence interval (95% CI) 0.92-0.98), 0.94 (95% CI 0.88-0.97), 0.93 (95% CI 0.76-0.98) respectively. The Bland-Altman plots showed that the 95% LOA were -0.17-0.12 (Pa) for group I, -0.09-0.13 (Pa) for group II and -0.08-0.10 (Pa) for group III. CONCLUSION: V Flow measurement is a simple, rapid and feasible imaging method for the WSS assessment of CCA in healthy volunteers, which will probably be an important tool for assessing CCA function.

An investigation of factors affecting elementary school students' BMI values based on the system dynamics modeling.

This study used system dynamics method to investigate the factors affecting elementary school students' BMI values. The construction of the dynamic model is divided into the qualitative causal loop and the quantitative system dynamics modeling. According to the system dynamics modeling, this study consisted of research on the four dimensions: student's personal life style, diet-relevant parenting behaviors, advocacy and implementation of school nutrition education, and students' peer interaction. The results of this study showed that students with more adequate health concepts usually have better eating behaviors and consequently have less chance of becoming obese. In addition, this study also verified that educational attainment and socioeconomic status of parents have a positive correlation with students' amounts of physical activity, and nutrition education has a prominent influence on changing students' high-calorie diets.

Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism.

Atherosclerosis is a complex inflammatory arterial disease, and oxidized low-density lipoprotein (oxLDL) is directly associated with chronic vascular inflammation. Previous studies have shown that Ginkgo biloba extract (GbE) acts as a therapeutic agent for neurological and cardiovascular disorders. However, the mechanisms mediating the actions of GbE are still largely unknown. In the present study, we tested the hypothesis that GbE protects against oxLDL-induced endothelial dysfunction via an AMP-activated protein kinase (AMPK)-dependent mechanism. Human umbilical vein endothelial cells were treated with GbE, followed by oxLDL, for indicated time periods. Results from Western blot showed that GbE inhibited the membrane translocation of the NADPH oxidase subunits p47(phox) and Rac-1 and attenuated the increase in protein expression of membrane subunits gp91 and p22(phox) caused by oxLDL-induced AMPK dephosphorylation and subsequent PKC activation. AMPK-α(1)-specific small interfering RNA-transfected cells that had been exposed to GbE followed by oxLDL revealed elevated levels of PKC and p47(phox). In addition, exposure to oxLDL resulted in reduced AMPK-mediated Akt/endothelial nitric oxide (NO) synthase signaling and the induction of phosphorylation of p38 mitogen-activated protein kinase, which, in turn, activated NF-κB-mediated inflammatory responses, such as the release of interleukin-8, the expression of the adhesion molecule, and the adherence of monocytic cells to human umbilical vein endothelial cells. Furthermore, oxLDL upregulated the expression of inducible NO synthase, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with GbE, however, exerted significant cytoprotective effects in a dose-dependent manner. Results from this study may provide insight into a possible molecular mechanism by which GbE protects against oxLDL-induced endothelial dysfunction.

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), originally identified as the major receptor for oxidized low-density lipoprotein (oxLDL) in endothelial cells, plays a major role in the pathology of vascular diseases. Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. In the present study, we hypothesized that the most abundant polyphenolic compound in tea, epigallocatechin-3-gallate (EGCG), can downregulate parameters of endothelial dysfunction by modulating LOX-1-regulated cell signaling. In cultured human umbilical vein endothelial cells (HUVECs), exposure to oxLDL (130 microg/ml), which led to an increase in LOX-1 expression at the RNA and protein levels, was abrogated by addition of EGCG or DPI, a well-known inhibitor of flavoproteins, suggesting the involvement of NADPH oxidase. Furthermore, oxLDL rapidly activated the membrane translocation of Rac-1 and p47phox and the subsequent induction of ROS generation, which was suppressed markedly by pretreatment with EGCG or anti-LOX-1 monoclonal antibody. OxLDL also increased p38 MAPK phosphorylation and decreased phosphorylation of the amino-terminal region of Akt, with maximal induction at about 30 min, and NF-kappaB phosphorylation within 1 h, resulting in redox-sensitive signaling. In addition, oxLDL diminished the expression of endothelial nitric oxide synthase (eNOS), enhanced the expression of endothelin-1 and adhesion molecules (ICAM, E-selectin, and monocyte chemoattractant protein-1), and increased the adherence of monocytic THP-1 cells to HUVECs. Pretreatment with EGCG, however, exerted significant cytoprotective effects in all events. These data suggest that EGCG inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent activation of NF-kappaB via the p38 MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which EGCG suppresses oxLDL-mediated vascular endothelial dysfunction.