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IMPORTANCE There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse.OBJECTIVE To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). DESIGN, SETTING, AND PARTICIPANTSIn this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020. EXPOSURES Data regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected. MAIN OUTCOMES AND MEASURESThe primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. RESULTS A total of 10 105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site. CONCLUSIONS AND RELEVANCESites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect (continued) Key Points Question In metastatic renal cell carcinoma (RCC), do patterns of metastasis differ between histologic subtypes and are sites of metastasis associated with survival? Findings In this cohort studyincluding 10 105 patients, patterns of metastasis varied significantly between metastatic clear cell RCC, papillary RCC, and chromophobe RCC. Sites of metastasis were associated with survival in all histologic subtype...

Vascular endothelial growth inhibitor (VEGI) is a novel anti-angiogenic cytokine that belongs to the tumour necrosis factor (TNF) superfamily. Very little is known about the significance of VEGI in cancer. Our study analysed VEGI expression in relation to breast cancer patient clinical parameters. The VEGI expression profile was assessed qualitatively (RT-PCR), quantitatively (real-time Quantitative-PCR), and immuno-histochemically (IHC), in a panel of 24 human normal and cancer cell lines and in a cohort of 151 mammary tissue samples (n = 33 normal breast tissue; n = 118 breast cancer tissue) with a 6-year median follow-up. Patients who had died of breast cancer or had local recurrence of the disease expressed significantly lower levels of VEGI in comparison to the elevated levels in the disease free patients. High levels of VEGI were associated with an increased chance of patient survival. Importantly, patients with breast tumours expressing reduced levels of VEGI had a poorer prognosis than those patients expressing high levels of VEGI. However, no significant correlations were observed between VEGI expression and tumour grade, TNM classification, or nodal involvement. In conclusion, VEGI is aberrantly expressed in human breast cancer tissues. VEGI displays prognostic relevance as breast cancer patients with an overall poor prognosis express significantly lower levels of VEGI compared to those with a favourable prognosis.

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West Nile virus (WNV) has spread rapidly around the globe, efficiently crossing species from migrating birds into humans and other mammals. The viral protease NS2B-NS3 is important for WNV replication and recognizes dibasic substrate sequences common to other flaviviral proteases but different from most mammalian proteases. Potent inhibitors of WNV protease with antiviral activity have been elusive to date. We report the smallest and most potent inhibitors known for this enzyme, cationic tripeptides with nonpeptidic caps at the N-terminus and aldehyde at the C-terminus. One of these, compound 3 ( Ki = 9 nM) is stable in serum (>90% intact after 3 h, 37 degrees C), cell permeable, and shows antiviral activity (IC 50 1.6 microM) without cytotoxicity (IC 50 >400 microM), thereby validating the approach of inhibiting WNV protease to suppress WNV replication.

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This paper presents an integrated multilevel converter of switched reluctance motors (SRMs) fed by a modular front-end circuit for plug-in hybrid electric vehicle (PHEV) applications. Several operating modes can be achieved by changing the on-off states of the switches in the front-end circuit. In generator driving mode, the battery bank is employed to elevate the phase voltage for fast excitation and demagnetization. In battery driving mode, the converter is reconfigured as a four-level converter, and the capacitor is used as an additional charge capacitor to produce multilevel voltage outputs, which enhances the torque capability. The operating modes of the proposed drive are explained and the phase current and voltage are analyzed in details. The battery charging is naturally achieved by the demagnetization current in motoring mode and by the regenerative current in braking mode. Moreover, the battery can be charged by the external AC source or generator through the proposed converter when the vehicle is in standstill condition. The SRM-based PHEV can operate at different speeds by coordinating the power flow between the generator and battery. Simulation in MATLAB/Simulink and experiments on a three-phase 12/8 SRM confirm the effectiveness of the proposed converter topology. Index Terms-Fast excitation and demagnetization, front-end circuit, multilevel voltage, flexible battery charging, plug-in hybrid electric vehicle (PHEV), switched reluctance motor (SRM).

Reliability of power converters is of crucial importance in switched reluctance motor drives used for safetycritical applications. Open-circuit faults in power converters will cause the motor to run in unbalanced states, and if left untreated, they will lead to damage to the motor and power modules, and even cause a catastrophic failure of the whole drive system. This study is focused on using a single current sensor to detect open-circuit faults accurately. An asymmetrical half-bridge converter is considered in this study and the faults of single-phase open and two-phase open are analysed. Three different bus positions are defined. On the basis of a fast Fourier transform algorithm with Blackman window interpolation, the bus current spectrums before and after open-circuit faults are analysed in details. Their fault characteristics are extracted accurately by the normalisations of the phase fundamental frequency component and double phase fundamental frequency component, and the fault characteristics of the three bus detection schemes are also compared. The open-circuit faults can be located by finding the relationship between the bus current and rotor position. The effectiveness of the proposed diagnosis method is validated by the simulation results and experimental tests.