Activity

Measuring adherence to ERCP quality indicators (QIs) is confounded by variability in indications, maneuvers, and documentation styles. We hypothesized that incorporation of mandatory, structured data fields within reporting software would permit accurate measurement of QI adherence rates and facilitate generation of a provider ERCP report card.

At two referral centers, endoscopy documentation software was modified to generate provider alerts prior to finalizing the note. The alerts reminded the provider to document the following components in a standardized manner indication, altered anatomy, prior interventions, and QIs deemed high priority by society consensus, study authors, or both. Adherence rates for each QI were calculated in aggregate and by provider via data extraction directly from the procedure documentation software. Medical records were reviewed manually to measure the accuracy of automated data extraction. YAP-TEAD Inhibitor 1 Accuracy of automated measurement for each QI was calculated against results derived by manual review.

During the 9-month study period, 1,376 ERCP procedures were completed by 8 providers. Manual medical record review confirmed high (98-100%) accuracy of automatic extraction of ERCP QIs from the endoscopy report, including cannulation rate of the native papilla and complete extraction of common bile duct stones. An ERCP report card was generated, allowing for individual comparison of adherence to ERCP QIs with colleagues at their institution and others.

In this pilot study, use of mandatory, structured data fields within clinical ERCP reports permit the accurate measurement of high priority ERCP QIs and the subsequent generation of interval report cards.

In this pilot study, use of mandatory, structured data fields within clinical ERCP reports permit the accurate measurement of high priority ERCP QIs and the subsequent generation of interval report cards.The understanding and prediction of the solubility of biomolecules, even of the simplest ones, reflect an open question and unmet need. Short aromatic tripeptides are among the most highly aggregative biomolecules. However, in marked contrast, Ala-Phe-Ala (AFA) was surprisingly found to be non-aggregative and could be solubilized at millimolar concentrations. Here, aiming to uncover the underlying molecular basis of its high solubility, we explore in detail the solubility, aggregation propensity, and atomic-level structure of the tripeptide. We demonstrate an unexpectedly high water solubility of AFA reaching 672 mM, two orders of magnitude higher than reported previously. The single crystal structure reveals an anti-parallel β sheet conformation devoid of any aromatic interactions. This study provides clear mechanistic insight into the structural basis of solubility and suggests a simple and feasible tool for its estimation, bearing implications for design of peptide drugs, peptides materials, and advancement of peptide nanotechnology.Force sensors that are thin, low-cost, flexible, and compatible with commercial microelectronic chips are of great interest for use in biomedical sensing, precision surgery, and robotics. By leveraging a combination of microfluidics and capacitive sensing, we develop a thin, flexible force sensor that is conformable and robust. The sensor consists of a partially filled microfluidic channel made from a deformable material, with the channel overlaying a series of interdigitated electrodes coated with a thin, insulating polymer layer. When a force is applied to the microfluidic channel reservoir, the fluid is displaced along the channel over the electrodes, thus inducing a capacitance change proportional to the applied force. The microfluidic molds themselves are made of low-cost sacrificial materials deposited via aerosol-jet printing, which is also used to print the electrode layer. We envisage a large range of industrial and biomedical applications for this force sensor.

Current rheumatoid arthritis therapies target immune inflammation and are subject to ceiling effects. Seliciclib is an orally available cyclin-dependent kinase inhibitor that suppresses proliferation of synovial fibroblasts-cells not yet targeted in rheumatoid arthritis. Part 1 of this phase 1b/2a trial aimed to establish the maximum tolerated dose of seliciclib in patients with active rheumatoid arthritis despite ongoing treatment with TNF inhibitors, and to evaluate safety and pharmacokinetics.

Phase 1b of the TRAFIC study was a non-randomised, open-label, dose-finding trial done in rheumatology departments in five UK National Health Service hospitals. Eligible patients (aged ≥18 years) fulfilled the 1987 American College of Rheumatology (ACR) or the 2010 ACR-European League Against Rheumatism classification criteria for rheumatoid arthritis and had moderate to severe disease activity (a Disease Activity Score for 28 joints [DAS28] of ≥3·2) despite stable treatment with anti-TNF therapy for at least 3 mmal efficacy trial.

UK Medical Research Council, Cyclacel, Research into Inflammatory Arthritis Centre (Versus Arthritis), and the National Institute of Health Research Newcastle and Birmingham Biomedical Research Centres and Clinical Research Facilities.

UK Medical Research Council, Cyclacel, Research into Inflammatory Arthritis Centre (Versus Arthritis), and the National Institute of Health Research Newcastle and Birmingham Biomedical Research Centres and Clinical Research Facilities.Angioimmunoblastic T cell lymphoma (AITL) and peripheral T cell lymphoma not-otherwise-specified (PTCL, NOS) have poor prognosis and lack driver actionable targets for directed therapies in most cases. Here we identify FYN-TRAF3IP2 as a recurrent oncogenic gene fusion in AITL and PTCL, NOS tumors. Mechanistically, we show that FYN-TRAF3IP2 leads to aberrant NF-κB signaling downstream of T cell receptor activation. Consistent with a driver oncogenic role, FYN-TRAF3IP2 expression in hematopoietic progenitors induces NF-κB-driven T cell transformation in mice and cooperates with loss of the Tet2 tumor suppressor in PTCL development. Moreover, abrogation of NF-κB signaling in FYN-TRAF3IP2-induced tumors with IκB kinase inhibitors delivers strong anti-lymphoma effects in vitro and in vivo. These results demonstrate an oncogenic and pharmacologically targetable role for FYN-TRAF3IP2 in PTCLs and call for the clinical testing of anti-NF-κB targeted therapies in these diseases.