Frederickkarlsen5632

The protozoan parasite Toxoplasma gondii lives inside a vacuole in the host cytosol where it is protected from host cytoplasmic innate immune responses. However, IFNγ-dependent cell-autonomous immunity can destroy the vacuole and the parasite inside. Toxoplasma strain differences in susceptibility to human IFNγ exist, but the Toxoplasma effector(s) that determine these differences are unknown. We show that in human primary fibroblasts, the polymorphic Toxoplasma-secreted effector GRA15 mediates the recruitment of ubiquitin ligases, including TRAF2 and TRAF6, to the vacuole membrane, which enhances recruitment of ubiquitin receptors (p62/NDP52) and ubiquitin-like molecules (LC3B, GABARAP). This ultimately leads to lysosomal degradation of the vacuole. In murine fibroblasts, GRA15-mediated TRAF6 recruitment mediates the recruitment of immunity-related GTPases and destruction of the vacuole. Thus, we have identified how the Toxoplasma effector GRA15 affects cell-autonomous immunity in human and murine cells. © 2020 The Authors.Malignant giant cell tumor of bone or soft tissue (MGCTBS) is one of the malignant tumors associated with poor prognosis. However, it remains controversial whether the combined treatment of both surgery and radiotherapy (surgery + RT) leads to better survival outcomes than surgical treatment alone (surgery alone) does for patients diagnosed with MGCTBS. We compared the two treatment strategies using the data provided by Surveillance, Epidemiology, and End Results (SEER) program. About 357 patients with MGCTBS who received either surgery + RT or surgery alone between 1975 and 2016 in the USA were identified and then matched based on their propensity scores estimated using the patients' baseline characteristics. We also performed a subgroup analysis for patients with high-grade and regional/distant tumor extension. Unadjusted Kaplan-Meier curves suggested that the surgery alone group had a better 10-year survival profile than the surgery + RT group. After propensity score matching, there was no statistical difference between the two treatment groups with respect to the 10-year cancer-specific survival and overall survival distributions. A subsequent subgroup analysis demonstrated that the surgery alone group has a similar 10-year survival comparing with the surgery + RT group for patients with high-grade and regional/distant tumor extension. The results of our study suggest that RT should not be recommended as a regular therapeutic method for MGCTBS, even for patients with high-grade histology and distant metastasis Clinical Significance This study may provide better decision making for surgeons dealing with malignant giant cell tumor of bone or soft tissue. Type of study Observation study. Level of evidence Level III. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.3 He NMR measurements were carried out for the gaseous mixtures of helium-3 with pure nitrogen and synthetic air as the solvents. It was found that 3 He shielding is linearly dependent on solvent density up to approx. 5 mol/L. At higher density of the gaseous solvent, the change of 3 He shielding is non-linear and especially distinct when helium-3 atoms can interact with two O2 molecules. The interaction with paramagnetic oxygen molecules can induce two kinds of 3 He shieding changes (1) due to the isotropic Fermi contact interaction and (2) from the dipolar magnetic interaction between unpaired O2 electrons and 3 He nuclear magnetic dipole moment. The two paramagnetic effects in helium-3 shielding cannot be experimentally seperated, though for such small molecular objects they could be presumably modelled by advanced theoretical calculations. This article is protected by copyright. All rights reserved.Methods for the evaluation of the predictive accuracy of biomarkers with respect to survival outcomes subject to right censoring have been discussed extensively in the literature. In cancer and other diseases, survival outcomes are commonly subject to interval censoring by design or due to the follow up schema. In this article, we present an estimator for the area under the time-dependent receiver operating characteristic (ROC) curve for interval censored data based on a nonparametric sieve maximum likelihood approach. We establish the asymptotic properties of the proposed estimator and illustrate its finite-sample properties using a simulation study. The application of our method is illustrated using data from a cancer clinical study. An open-source R package to implement the proposed method is available on Comprehensive R Archive Network. © 2020 John Wiley & Sons, Ltd.COVID-19 is the latest global pandemic caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). There have been seven pathogenic Human Coronaviruses (HCoVs) which cause respiratory infections. Common cold coronaviruses HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1 are the four endemic HCoVs. SARS-CoV-1, MERS-CoV, SARS-CoV-2 are zoonotic emerging epidemic pathogens with significant morbidity, mortality and economic impact. The endemic HCoVs have been known to cause co-infections or can be co-detected with each other or with other respiratory viruses. In general, respiratory viral co-infections are recognized more commonly today with the use of respiratory multiplex molecular diagnostic panels. Clinicians need to be aware of co-infections among HCoVs. A high degree of suspicion in this rapidly evolving outbreak is required in order to make the diagnosis. This is vital if we are to try and contain and control the spread of the COVID-19. BAY-876 in vivo This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Escherichia coli O157H7 (E. coli O157H7) is an important pathogenic Bacterium that threatens human health. A convenient, sensitive and specific method for the E. coli O157H7 detection is necessary. We developed two pairs of monoclonal antibodies through traditional hybridoma technology, one specifically against E. coli O157 antigen and the other specifically against E. coli H7 antigen. Using these two pairs of antibodies, we developed two rapid test kits to specifically detect E. coli O157 antigen and E. coli H7 antigen, respectively. The detection sensitivity for O157 positive E. coli is 1x103 CFU ml-1 and for H7 positive E. coli is 1x104 CFU ml-1 . Combining these two pairs of antibodies together, we developed a combo test strip that can specifically detect O157 H7, with a detection sensitivity of 1x104 CUF ml-1 , when two detection lines are visible to the naked eye. This is currently the only rapid detection reagent that specifically detects O157 H7 by simultaneously detecting O157 antigen and H7 antigens of E. coli. Our product has advantages of simplicity and precision, and can be a very useful on-site inspection tool for accurate and rapid detection of E. coli O157H7 infection. This article is protected by copyright. All rights reserved.OBJECTIVE This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND AND AIMS Hepatitis B core related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. METHODS Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in 3 serial serum samples for each patient. Patients were divided into 6 groups for analysis HBeAg-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI) and HBsAg seroclearance (SS). RESULTS 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with HBV DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥6.0 log U/ml could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve [AUROC] 0.99, p less then 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥4.0 log U/ml could best differentiate ENH from ENI (AUROC 0.81; p less then 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63% and 89% patients in ENH, ENI, and SS groups at the last visit, respectively. CONCLUSIONS HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease. © 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.The purpose of the study was to evaluate the accuracy of a commercial automatic digital templating algorithm compared to manual digital templating in total knee arthroplasty (TKA). The study also evaluated if race and the presence of a standardized calibration marker on preoperative radiographs effect the accuracy of digital templating. One hundred twenty-five consecutive patients undergoing primary TKA were included in the study. Patient demographics, etiology of arthritis, and the presence of a standardized calibration marker on preoperative anteroposterior (AP) and lateral radiographs was recorded. Manual digital templating and the use of the "auto-knee" templating algorithm with "Traumacad" software was performed and recorded. Intraoperative sizes of the actual implants used were recorded. Pearson χ2 test was used to evaluate the accuracy of auto versus manual templating. Manual templating was within 1 size of the implant used intraoperatively for femoral and tibial implants 97.6% and 94.2% of the time, respectively. The "auto-knee" algorithm was within one size of the implant used for femoral and tibial implants 51.2% and 71.2% of the time, respectively. The presence of a standardized calibration marker on the AP view did not change accuracy of templating for both components. There was no difference in accuracy of templating between races. We caution surgeons from exclusively using an automatic algorithm as it is less accurate than manual templating for TKA. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.