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- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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3. |
- Campbell, C., et al.
(författare)
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Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:14
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD).Materials & methods:Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] >= 300-<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48.Results:Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; >= 300-<400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109.Conclusion:These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD >= 300-<400 m (the ambulatory transition phase), thereby informing future trial design.
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4. |
- Goldfarb, Y, et al.
(författare)
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Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation
- 2021
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:11
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Tidskriftsartikel (refereegranskat)abstract
- The autoimmune regulator (AIRE) is essential for the establishment of central tolerance and prevention of autoimmunity. Interestingly, different AIRE mutations cause autoimmunity in either recessive or dominant-negative manners. Using engineered mouse models, we establish that some monoallelic mutants, including C311Y and C446G, cause breakdown of central tolerance. By using RNAseq, ATACseq, ChIPseq, and protein analyses, we dissect the underlying mechanisms for their dominancy. Specifically, we show that recessive mutations result in a lack of AIRE protein expression, while the dominant mutations in both PHD domains augment the expression of dysfunctional AIRE with altered capacity to bind chromatin and induce gene expression. Finally, we demonstrate that enhanced AIRE expression is partially due to increased chromatin accessibility of the AIRE proximal enhancer, which serves as a docking site for AIRE binding. Therefore, our data not only elucidate why some AIRE mutations are recessive while others dominant, but also identify an autoregulatory mechanism by which AIRE negatively modulates its own expression.
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- Krakhmalnyi, M., et al.
(författare)
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Species Diversity of Lycoperdaceae (Agaricales) in Israel, with Some Insights into the Phylogenetic Structure of the Family
- 2023
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Ingår i: Journal of fungi (JoF). - 2309-608X. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- The diversity of Lycoperdaceae in Israel was studied. Molecular phylogenetic relationships within the family, and genus Lycoperdon in particular, were inferred using original ITS rDNA sequences of 58 samples belonging to 25 species from Israel and six other countries, together with 66 sequences stored in the GenBank database. The current molecular phylogenetic study recovered the family Lycoperdaceae as a monophyletic group, which was supported in both maximum likelihood and Bayesian analyses. The clades corresponding to the genera Apioperdon, Bovista, Calvatia, Disciseda, and Lycoperdon were revealed. The taxonomic structure of the named genera was partially resolved. Within the genus Lycoperdon, some species received significant statistical support; however, their relationships, as well as the problem of the genus monophyly, mostly remained questionable. As a result of a thorough literature survey, extensive sample collection, and studies of the material stored in the Herbarium of the Institute of Evolution, University of Haifa (HAI, Israel), fifteen species representing five genera were found in the territory of Israel. Six species, namely Apioperdon pyriforme, Bovista aestivalis, Calvatia candida, Lycoperdon decipiens, L. niveum, and L. perlatum, are new additions to the diversity of Lycoperdaceae in Israel. Detailed macro- and micromorphological descriptions, ecology, geography, and critical notes, together with light microscopy photos and SEM micrographs, are provided. In-depth discussion on some taxonomically challenging species is presented.
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- Sudheshwar, A., et al.
(författare)
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Assessing sustainability hotspots in the production of paper-based printed electronics
- 2023
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Ingår i: Flexible and Printed Electronics. - : Institute of Physics. - 2058-8585. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Novel printed electronics are projected to grow and be manufactured in the future in large volumes. In many applications, printed electronics are envisaged as sustainable alternatives to conventional (PCB-based) electronics. One such application is in the semi-quantitative drug detection and point-of-care device called ‘GREENSENSE’ that uses paper-based printed electronics. This paper analyses the carbon footprint of GREENSENSE in order to identify and suggest means of mitigating disproportionately high environmental impacts, labeled ‘sustainability hotspots’, from materials and processes used during production which would be relevant in high-volume applications. Firstly, a life cycle model traces the flow of raw materials (such as paper, CNCs, and nanosilver) through the three ‘umbrella’ processes (circuit printing, component mounting, and biofunctionalization) manufacturing different electronic components (the substrate, conductive inks, energy sources, display, etc) that are further assembled into GREENSENSE. Based on the life cycle model, life cycle inventories are modeled that map out the network of material and energy flow throughout the production of GREENSENSE. Finally, from the environmental impact and sustainability hotspot analysis, both crystalline nanocellulose and nanosilver were found to create material hotspots and they should be replaced in favor of lower-impact materials. Process hotspots are created by manual, lab-, and pilot-scale processes with unoptimized material consumption, energy use, and waste generation; automated and industrial-scale manufacturing can mitigate such process hotspots. © 2023 The Author(s).
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- Hernandez, O. J., et al.
(författare)
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A Statistical Analysis of the Nuclear Structure Uncertainties in μD
- 2020
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Ingår i: Springer Proceedings in Physics. - Cham : Springer International Publishing. - 0930-8989 .- 1867-4941. ; 238, s. 833-837
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Konferensbidrag (refereegranskat)abstract
- The charge radius of the deuteron (D), was recently determined to three times the precision compared with previous measurements using the measured Lamb shift in muonic deuterium ((formula presented)D). However, the (formula presented)D value is 5.6 (formula presented) smaller than the world averaged CODATA-2014 value (Pohl R et al. (2016) Science 353:669 [1]). To shed light on this discrepancy we analyze the uncertainties of the nuclear structure calculations of the Lamb shift in (formula presented)D and conclude that nuclear theory uncertainty is not likely to be the source of the discrepancy.
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- Hernandez, O. J., et al.
(författare)
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The deuteron-radius puzzle is alive: A new analysis of nuclear structure uncertainties
- 2018
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 778, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- To shed light on the deuteron radius puzzle we analyze the theoretical uncertainties of the nuclear structure corrections to the Lamb shift in muonic deuterium. We find that the discrepancy between the calculated two-photon exchange correction and the corresponding experimentally inferred value by Pohl etal. [1] remain. The present result is consistent with our previous estimate, although the discrepancy is reduced from 2.6 sigma about 2 sigma. The error analysis includes statistic as well as systematic uncertainties stemming from the use of nucleon-nucleon interactions derived from chiral effective field theory at various orders. We therefore conclude that nuclear theory uncertainty is more likely not the source of the discrepancy. (c) 2018 The Authors. Published by Elsevier B.V.
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