Notes

Cnm1 mediates nucleus-mitochondria contact website formation in response to phospholipid quantities.
The immunoblotting technique (also known as Western blotting) is an essential tool used in biomedical research to determine the relative size and abundance of specific proteins, as well as protein modifications. However, long incubation times severely limit its throughput. We have devised a system that improves antigen binding by cyclic draining and replenishing (CDR) of the antibody solution in conjunction with an immunoreaction enhancing agent. Biochemical analyses revealed that the CDR method reduced the incubation time of the antibodies, and the presence of a commercial immunoreaction enhancing agent altered the affinity of the antibody, respectively. Combination of the CDR method with the immunoreaction enhancing agent considerably enhanced the output signal and further reduced the incubation time of the antibodies. The resulting high-speed immunoblot can be completed in 20 minutes without any loss in sensitivity. Further, the antibodies are fully reusable. This method is effective for both chemiluminescence and fluorescence detection. Widespread adoption of this technique could dramatically boost efficiency and productivity across the life sciences. Published by Oxford University Press on behalf of the Japanese Biochemical Society 2020.Electronic health record (EHR) log data have shown promise in measuring physician time spent on clinical activities, contributing to deeper understanding and further optimization of the clinical environment. In this article, we propose 7 core measures of EHR use that reflect multiple dimensions of practice efficiency total EHR time, work outside of work, time on documentation, time on prescriptions, inbox time, teamwork for orders, and an aspirational measure for the amount of undivided attention patients receive from their physicians during an encounter, undivided attention. We also illustrate sample use cases for these measures for multiple stakeholders. Finally, standardization of EHR log data measure specifications, as outlined here, will foster cross-study synthesis and comparative research. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.Pragmatic clinical trials often entail the use of electronic health record (EHR) and claims data, but bias and quality issues associated with these data can limit their fitness for research purposes particularly for study end points. Patient-reported health (PRH) data can be used to confirm or supplement EHR and claims data in pragmatic trials, but these data can bring their own biases. Moreover, PRH data can complicate analyses if they are discordant with other sources. Using experience in the design and conduct of multi-site pragmatic trials, we itemize the strengths and limitations of PRH data and identify situational criteria for determining when PRH data are appropriate or ideal to fill gaps in the evidence collected from EHRs. To provide guidance for the scientific rationale and appropriate use of patient-reported data in pragmatic clinical trials, we describe approaches for ascertaining and classifying study end points and addressing issues of incomplete data, data alignment, and concordance. We conclude by identifying areas that require more research. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email [email protected] The study sought to describe key features of clinical concepts and data required to implement clinical practice recommendations as clinical decision support (CDS) tools in electronic health record systems and to identify recommendation features that predict feasibility of implementation. MATERIALS AND METHODS Using semistructured interviews, CDS implementers and clinician subject matter experts from 7 academic medical centers rated the feasibility of implementing 10 American College of Emergency Physicians Choosing Wisely Recommendations as electronic health record-embedded CDS and estimated the need for additional data collection. Ratings were combined with objective features of the guidelines to develop a predictive model for technical implementation feasibility. RESULTS A linear mixed model showed that the need for new data collection was predictive of lower implementation feasibility. The number of clinical concepts in each recommendation, need for historical data, and ambiguity of clinical concepts were not predictive of implementation feasibility. CONCLUSIONS The availability of data and need for additional data collection are essential to assess the feasibility of CDS implementation. Authors of practice recommendations and guidelines can enable organizations to more rapidly assess data availability and feasibility of implementation by including operational definitions for required data. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email [email protected] To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery. METHODS Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial-mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model. RESULTS We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P less then 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P less then 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo. CONCLUSIONS Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma. © 2020 The Author(s).Peroxisomal matrix proteins are imported into peroxisomes in a process mediated by peroxisomal targeting signal (PTS) type 1 and 2. The PTS2 proteins are imported into peroxisomes after binding with Pex7p. Niwa et al. identified a novel Pex7p-binding protein in CHO cells and characterized the subcellular distribution and molecular properties of the human homolog, "P7BP2" (J. Biochem. 2018; 164 437-447). Interestingly, P7BP2 possesses PTS2 at the NH2-terminal and six putative AAA+ domains. Another group has suggested that the protein also possesses mitochondrial targeting signal at the NH2-terminal. In fact, the P7BP2 expressed in mammalian cells is targeted to both peroxisomes and mitochondria. The purified protein from Sf9 cells is a monomer and has a disc-like ring structure, suggesting that P7BP2 is a novel dynein-type AAA+ family protein. The protein expressed in insect cells exhibits ATPase activity. P7BP2 localizes to peroxisomes and mitochondria, and has a common function related to dynein type ATPases in both organelles. © The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.Importance The increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer. Objective To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer. Design, Setting, and Participants For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017. Exposures Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions. Main Outcomes and Measurethogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76 (95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance. Conclusions and Relevance Women with pathogenic variants in BRCA1/2 and other breast cancer-associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.Antibodies can recognize various types of antigens with high specificity and affinity and peptide is one of their major targets. Understanding an antibody's molecular recognition mechanism for peptide is important for developing clones with a higher specificity and affinity. Here I review recent progresses in flexible peptide recognition by an antibody using several biophysical techniques, including x-ray crystallography, molecular dynamics simulations, and calorimetric measurements. A set of two reports highlight the importance of intramolecular hydrogen bonds that form in an unbound flexible state. Such intramolecular hydrogen bonds restrict the fluctuation of the peptide and reduce the conformational entropy, resulting in the destabilization of the unbound state and increasing the binding affinity by increasing the free energy change. These detailed analyses will aid in the antibody design in the future. find more © The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.Importance Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. Objective To quantify the association between patients' adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. Design, Setting, and Participants This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. Exposures Visit adherence was measured in 4 ways total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended).
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