Objective. To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations.Methods. Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by realtime polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National AssessmentSystemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite.Results. Each gene was highly expressed in SLE patients compared with normal controls (P < 0.0003) or disease controls (P < 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P ‫؍‬ 0.001), the SELENA-SLEDAI flare score (P ‫؍‬ 0.03), and the physician's global assessment score (P ‫؍‬ 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P ‫؍‬ 0.007) or hypocomplementemia (P ‫؍‬ 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P ‫؍‬ 0.02) and were positively associated with proteinuria (P ‫؍‬ 0.009).Conclusion. The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation resulting in the production of antinuclear and other autoantibodies, generation of circulating immune complexes, and activation of the complement system. The disease course of SLE is heterogeneous, affecting different individuals with a wide range of manifestations. Unpredictable flares and improvements may be observed. There is no specific single diagnostic test for SLE, and therapy is typically initiated after signs of

Differentiation of insulin-producing pancreatic β cells from induced pluripotent stem cells (iPSCs) derived from patients with diabetes promises to provide autologous cells for diabetes cell replacement therapy. However, current approaches produce patient iPSC-derived β (SC-β) cells with poor function in vitro and in vivo. Here, we used CRISPR-Cas9 to correct a diabetes-causing pathogenic variant in Wolfram syndrome 1 (WFS1) in iPSCs derived from a patient with Wolfram syndrome (WS). After differentiation to β cells with our recent six-stage differentiation strategy, corrected WS SC-β cells performed robust dynamic insulin secretion in vitro in response to glucose and reversed preexisting streptozocin-induced diabetes after transplantation into mice. Single-cell transcriptomics showed that corrected SC-β cells displayed increased insulin and decreased expression of genes associated with endoplasmic reticulum stress. CRISPR-Cas9 correction of a diabetes-inducing gene variant thus allows for robust differentiation of autologous SC-β cells that can reverse severe diabetes in an animal model.

Can engaging college students in client‐centered projects in science, technology, engineering, and mathematics (STEM) coursework increase interest in STEM professions? The current study explored the effectiveness of project‐based learning (PjBL) courses on student attitudes, major choice, and career aspirations in STEM. Framed in expectancy‐value and social cognitive career choice models, we examined the effect of engaging in at least one authentic, project‐based course during the first four semesters of college on student STEM attitudes and career aspirations in a quasi‐experimental study with a sample of (N = 492) natural science and engineering students. STEM self‐efficacy and subjective task value variables (STEM attainment, intrinsic and utility value of STEM courses, and relative cost associated with engaging in STEM courses) were examined as mediators of the relationship between classroom project‐based experiences and STEM career aspirations. Gender and underrepresented minority status were also examined. We found that engaging in at least one project‐based course during the first four semesters affected student perceptions of STEM skills, perceptions of the utility value of participating in STEM courses, and STEM career aspirations. Furthermore, we found that the effect of project‐based courses on STEM career aspirations was mediated by STEM skills and perceptions of course utility. The effect of PjBL was not moderated by race or gender. We highlight areas of future research and the promise of PjBL for engaging students in STEM professions.

Duchenne muscular dystrophy is caused by dystrophin mutations that lead to structural instability of the sarcolemma membrane, myofiber degeneration/regeneration and progressive muscle wasting. Here we show that myogenic Akt signaling in mouse models of dystrophy promotes increased expression of utrophin, which replaces the function of dystrophin thereby preventing sarcolemma damage and muscle wasting. In contrast to previous suggestions that increased Akt in dystrophy was a secondary consequence of pathology, our findings demonstrate a pivotal role for this signaling pathway such that modulation of Akt can significantly affect disease outcome by amplification of existing, physiological compensatory mechanisms.

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta‐analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5‐year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta‐regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.