5,885 research outputs found

    Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors:Real-World Data from a Pooled Multicenter Analysis

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    BACKGROUND: Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce. PATIENTS AND METHODS: Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient’s imaging procedures to their demographics, tumor–treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE. RESULTS: The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings. CONCLUSION: Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients’ individual risk profiles for LRR

    Simulation of the CMS Resistive Plate Chambers

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    The Resistive Plate Chamber (RPC) muon subsystem contributes significantly to the formation of the trigger decision and reconstruction of the muon trajectory parameters. Simulation of the RPC response is a crucial part of the entire CMS Monte Carlo software and directly influences the final physical results. An algorithm based on the parametrization of RPC efficiency, noise, cluster size and timing for every strip has been developed. Experimental data obtained from cosmic and proton-proton collisions at s=7\sqrt{s}=7 TeV have been used for determination of the parameters. A dedicated validation procedure has been developed. A good agreement between the simulated and experimental data has been achieved.Comment: to be published in JINS

    Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control

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    The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1, are associated with early-onset familial Parkinson’s disease and lead to pathological oxidative stress and/or disrupted protein degradation by the proteasome. The aim of this study was to gain insights into the pathogenic mechanisms of selected DJ-1 missense mutations, by characterizing protein–protein interactions, core parameters of mitochondrial function, quality control regulation via autophagy, and cellular death following dopamine accumulation. We report that the DJ-1M26I mutant influences DJ-1 interactions with SUMO-1, in turn enhancing removal of mitochondria and conferring increased cellular susceptibility to dopamine toxicity. By contrast, the DJ-1D149A mutant does not influence mitophagy, but instead impairs Ca2+ dynamics and free radical homeostasis by disrupting DJ-1 interactions with a mitochondrial accessory protein known as DJ-1-binding protein (DJBP/EFCAB6). Thus, individual DJ-1 mutations have different effects on mitochondrial function and quality control, implying mutation-specific pathomechanisms converging on impaired mitochondrial homeostasis
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