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The purpose of this study was to compare the diagnostic performance of ultrasonography (US) and mammography in the differential diagnosis of breast lesions after adding different types of elastography to US.This institutional review board-approved study included 316 breast lesions in 289 women between July 2016 and July 2018. All these lesions were evaluated with conventional US, elastography, and mammography before biopsy or surgery. Elastography, including elasticity imaging (EI), virtual touch tissue imaging (VTI), and virtual touch imaging quantification (VTIQ), were used to downgrade US Breast Imaging-Reporting and Data System category 4A lesions. Diagnostic performances were calculated for mammography, US elastography, and the combination of US and elastography.The sensitivity of US (100%) was significantly higher than that of mammography (84.6%; P .001), but the specificity of US (14.5%) was significantly lower than that of mammography (59.1%; P .001). After adding EI, VTI, and VTIQ to US, the specificity was significantly increased from 14.5% to 69.4%, 72.6%, and 78.0%, respectively (P .001), and were significantly higher than that of mammography (P = .043, P = .006, and P .001, respectively). The sensitivity of US + EI (96.2%) and US + VTI (96.2%) was lower than that of US alone, although not significantly (100%; P = .063 and P = .063, respectively).The addition of different types of elastography to US improved the diagnostic performance in the differential diagnosis of breast lesions when compared with mammography.

The aim of our study was to compare strain elastography (SE), acoustic radiation force impulse-inducing Virtual Touch Imaging ([VTI] Siemens Medical Solutions, Mountain View, CA, USA), Virtual Touch Imaging Quantification ([VTIQ] Siemens Medical Solutions) and combined methods in the evaluation of ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4 lesions to explore an applicable way to reduce unnecessary biopsy by reducing false positives of conventional US without yielding false-negative cases. A total of 267 patients with 278 BI-RADS category 4 lesions (151 benign and 127 malignant) were evaluated with conventional B-mode US, SE, VTI and VTIQ implemented on a Siemens Acuson S2000 US system. Diagnostic performance, including area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were evaluated. Overall, VTI alone exhibited the highest NPV (91.74%), although combined elastic methods exhibited higher NPV than single methods, with the highest NPV at 100% when the VTI, SE and VTIQ methods were combined. Compared with conventional US, PPV increased from 45.7% (127 of 278) to 63.18% (127 of 201) when adding combined elastography (VTI + SE +VTIQ). In addition, 52.5% (63/120) and 50.8% (61/120) of BI-RADS 4 A lesions were downgraded when using combined methods (VTI + SE and VTI + SE + VTIQ, respectively) without missing any cancer. However, 2 intraductal papillomas and 1 phyllodes tumor were not identified. In conclusion, the combination of different elastic methods have the potential to downgrade BI-RADS 4A lesions to reduce false-positive biopsies without increasing the risk of missing cancers.

To assess the diagnostic performance of the LR-M criteria of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 in differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in patients with and without risk factors for HCC. Fifty-four ICC in patients with risks and 55 ICC in patients without risks and matched control cases of HCC with and without risks (n = 59 and n = 55, respectively) were enrolled. The enhanced features of the lesions were retrospectively analyzed according to LR-M criteria. The diagnostic performances including the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of LR-M criteria were assessed. Peripheral rim-like hyperenhancement, early washout (

The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the host ubiquitin (Ub)‐conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40Ub and Lys92UBE2N, which leads to inhibition of signaling in the NF‐κB pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self‐ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are poorly understood at the molecular level. This study reports the structure of the MavC–UBE2N–Ub ternary complex representing a snapshot of MavC‐catalyzed crosslinking of UBE2N and Ub, which reveals the way by which UBE2N–Ub binds to the Insertion and Tail domains of MavC. Based on the structural and experimental data, the catalytic mechanism for the deamidase and transglutaminase activities of MavC is proposed. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC‐induced UBE2N ubiquitination, several essential regions and two key residues (Trp255MavC and Phe268MvcA) responsible for their respective enzymatic activities are identified. The results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA in terms of regulation of UBE2N ubiquitination., The pathogen Legionella pneumophila evades immune detection by deploying the transglutaminase effector MavC to ubiquitinate the host ubiquitin‐conjugating enzyme UBE2N. This work presents the structure of MavC–UBE2N–Ub ternary complex and sheds light on the molecular basis for MavC‐induced transglutamination and its mechanistic differences with its homolog MvcA, which counteracts MavC activity by deubiquitinating modified UBE2N in later phases of infection.

The Legionella pneumophila effector MavC induces ubiquitination of the E2 ubiquitin‐conjugating enzyme UBE2N by transglutamination, thereby abolishing its function in the synthesis of K(63)‐type polyubiquitin chains. The inhibition of UBE2N activity creates a conundrum because this E2 enzyme is important in multiple signaling pathways, including some that are important for intracellular L. pneumophila replication. Here, we show that prolonged inhibition of UBE2N activity by MavC restricts intracellular bacterial replication and that the activity of UBE2N is restored by MvcA, an ortholog of MavC (50% identity) with ubiquitin deamidase activity. MvcA functions to deubiquitinate UBE2N‐Ub using the same catalytic triad required for its deamidase activity. Structural analysis of the MvcA‐UBE2N‐Ub complex reveals a crucial role of the insertion domain in MvcA in substrate recognition. Our study establishes a deubiquitination mechanism catalyzed by a deamidase, which, together with MavC, imposes temporal regulation of the activity of UBE2N during L. pneumophila infection.

OBJECTIVES To evaluate the association between shear wave elastography parameters using virtual touch tissue imaging quantification (VTIQ) and the Ki-67 index in luminal-type breast cancer. METHODS Eighty-one patients with 82 lesions of pathologic confirmed luminal-type breast cancer underwent virtual touch tissue imaging quantification examination before surgery between December 2015 and June 2016. Patients were divided into 2 groups according to the Ki-67 index (≥14% versus

Background This study was aimed to assess whether ultrasonic spectrum analysis of radiofrequency (RF) time series using a clinical ultrasound system allows for early differentiating between the chemotherapy responders and nonresponders in human breast cancer xenografts that imitate clinical responding and nonresponding tumors. Methods Clinically responding (n = 20; MCF-7) and nonresponding (n = 20; MBA-MD-231) breast cancer xenografts were established in 40 nude mice. Ten mice from each group received either chemotherapy (adriamycin, 4 mg/kg) or saline as controls. Each tumor was imaged longitudinally with a clinical ultrasound scanner at baseline (day 0) and subsequently on days 2, 4, 6, 8 and 12 following treatment, and the corresponding RF time-series data were collected. Changes in six RF time-series parameters (slope, intercept, S1, S2, S3 and S4) were compared with the measurement of the tumor cell density, and their differential performances of the treatment response were analyzed. Results Adriamycin significantly inhibited tumor growth and decreased the cancer cell density in responders (P 0.05). Fold changes of slope were significantly increased in responders two days after adriamycin treatment (P = 0.002), but not in nonresponders (P > 0.05). Early changes in slope on day 2 could differentiate the treatment response in 100% of both responders (95% CI, 62.9–100.0%) and nonresponders (95% CI, 88.4–100%). Conclusions Ultrasonic RF time series allowed for the monitoring of the tumor response to chemotherapy and could further serve as biomarkers for early differentiating between the treatment responders and nonresponders. Electronic supplementary material The online version of this article (10.1186/s40644-019-0248-y) contains supplementary material, which is available to authorized users.

OBJECTIVE To determine the added value of a shear-wave elastography (SWE) quality map (QM) in the diagnosis of breast lesions and in predicting the biological characteristics of invasive breast cancer. MATERIALS AND METHODS Between January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWVmean), max SWV (SWVmax), and standard deviation (SD) with QM guidance (SWVmean + QM, SWVmax + QM, and SD + QM, respectively) and without QM guidance (SWVmean - QM, SWVmax - QM, and SD - QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance. RESULTS Of the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWVmean + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWVmean - QM (3.29 ± 1.22 m/s) and SD - QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWVmean + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWVmean - QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD - QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWVmean + QM (all p < 0.05), while only lymphovascular involvement showed higher SWVmean - QM (p = 0.036). CONCLUSION The use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.

The aim of this study was to evaluate whether quantitative analysis of elastic heterogeneity (EH) could improve the diagnostic performance of shear wave elastography (SWE) in breast lesions. From August 2016 to August 2017, 280 patients were enrolled in this prospective study. All lesions were evaluated with the ultrasound Breast Imaging Reporting and Data System (BI-RADS) and SWE with Virtual Touch tissue imaging quantification. The shear wave velocity (SWV) of the three areas of highest stiffness and lowest stiffness within the lesions were measured to calculate the maximum SWV (SWVmax), mean SWV (SWVmean) and EH. The EH was determined as the difference between the averaged highest SWV and lowest SWV. The diagnostic performance-including the area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity of BI-RADS, EH, SWVmax and SWVmean-were analyzed. The AUC of EH, SWVmax and SWVmean were 0.963, 0.949 and 0.937, respectively. The sensitivity of EH was 93.75%, which was significantly higher than that of SWVmax (84.37%) and SWVmean (84.37%) (p 0.05). For category 4A lesions, EH predicted all the malignant lesions, while two cancers were misdiagnosed by SWVmax and SWVmean, respectively. Quantitative analysis of EH can improve the sensitivity of SWE for the differential diagnosis of breast lesions without loss of specificity.

To determine whether a combination of different types of elastography could improve the accuracy of elastography-aided downgrading ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4a lesions. From January 2016 to May 2018, 458 consecutive women with 494 US BI-RADS category 4a breast lesions were enrolled in the prospective study. These lesions were subject to conventional US supplemented with strain elastography of elasticity imaging (EI), virtual touch tissue imaging (VTI), and shear wave elastography of virtual touch imaging quantification (VTIQ). Diagnostic performances were calculated for BI-RADS, EI, VTI, and VTIQ as well as the combination of EI, VTI, and VTIQ (combination of EI and VTI [EI + VTI], combination of EI and VTIQ [EI + VTIQ], and combination of VTI and VTIQ [VTI + VTIQ]). Pathologically, 445 lesions (90.1%) were benign, and 49 (9.9%) were malignant. The specificities of EI, VTI, and VTIQ were significantly higher than those of BI-RADS (69.9%, 83.8%, 75.5% vs. 0, respectively, P