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排序方式: 共有10000条查询结果,搜索用时 218 毫秒
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Jo-Lynn S. Tan Niranjan Sathianathen Marcus Cumberbatch Prokar Dasgupta Alexandre Mottrie Ronney Abaza Koon Ho Rha Thyavihally B. Yuvaraja Dipen J. Parekh Umberto Capitanio Rajesh Ahlawat Sudhir Rawal Nicolò M. Buffi Ananthakrishnan Sivaraman Kris K. Maes Gagan Gautam Francesco Porpiglia Levent Turkeri Mahendra Bhandari Benjamin Challacombe James Roscoe Porter Craig R. Rogers Daniel A. Moon 《BJU international》2021,128(Z3):30-35
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Natacha Martin Anne Bergougnoux Nesrine Baatallah Benoit Chevalier Jessica Varilh David Baux Bruno Costes Pascale Fanen Caroline Raynal Isabelle Sermet-Gaudelus Emmanuelle Girodon Magali Taulan-Cadars Alexandre Hinzpeter 《Journal of cystic fibrosis》2021,20(3):464-472
BackgroundMinigenes and in silico prediction tools are commonly used to assess the impact on splicing of CFTR variants. Exon skipping is often neglected though it could impact the efficacy of targeted therapies. The aim of the study was to identify exon skipping associated with CFTR variants and to evaluate in silico predictions of seven freely available software.MethodsCFTR basal exon skipping was evaluated on endogenous mRNA extracted from non-CF nasal cells and on two CFTR minigene banks. In silico tools and minigene systems were used to evaluate the impact of CFTR exonic variants on exon skipping.ResultsData showed that out of 65 CFTR variants tested, 26 enhanced exon skipping and that in silico prediction efficacy was of 50%-66%. Some in silico tools presented predictions with a bias towards the occurrence of splicing events while others presented a bias towards the absence of splicing events (non-detection including true negatives and false negatives). Classification of exons depending on their basal exon skipping level increased prediction rates up to 80%.ConclusionThis study indicates that taking basal exon skipping into account could orientate the choice of the in silico tools to improve prediction rates. It also highlights the need to validate effects using in vitro assays or mRNA studies in patients. Eventually, it shows that variant-guided therapy should also target exon skipping associated with variants. 相似文献
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Jignesh K. Patel Guillaume Coutance Alexandre Loupy Deanna Dilibero Michele Hamilton Michelle Kittleson Evan Kransdorf Babak Azarbal Osamu Seguchi Xiaohai Zhang David Chang Dael Geft Lawrence Czer Shaida Varnous Jon A. Kobashigawa 《American journal of transplantation》2021,21(7):2479-2488
Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037. 相似文献
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Marion G. Peters Shyam Kottilil Norah Terrault Dominic Amara Jennifer Husson Shirish Huprikar Sander Florman Mark S. Sulkowski Christine M. Durand Anne F. Luetkemeyer Rodney Rogers Joshua Grab Brandy Haydel Emily Blumberg Lorna Dove Jean Emond Kim Olthoff Coleman Smith Thomas Fishbein Henry Masur Peter G. Stock 《American journal of transplantation》2021,21(5):1780-1788
Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre– or post–liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6–29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre–LT and 26 post–LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre–LT and three post–LT. Overall, transplant free survival was 42.8% at 4 years and post–LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post–LT, with post–LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients. 相似文献
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