| 1. |
- van Huizen, Astrid M., et al.
(författare)
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International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis
- 2022
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Ingår i: JAMA dermatology. - : American Medical Association (AMA). - 2168-6068 .- 2168-6084. ; 158:5, s. 561-561
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Tidskriftsartikel (refereegranskat)abstract
- Importance A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.Objective To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.Design, Setting, and Participants Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).Main Outcomes and Measures In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.Results Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.Conclusions and Relevance In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
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| 2. |
- Leclerc, D., et al.
(författare)
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Gene Editing Corrects In Vitro a G > A GLB1 Transition from a GM1 Gangliosidosis Patient
- 2023
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Ingår i: Crispr Journal. - : Mary Ann Liebert Inc. - 2573-1599 .- 2573-1602. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced beta-galactosidase (beta-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. In this study, we show that 41% of GLB1 pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of beta-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient's cells, except a bystander edit without consequences on beta-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis.
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| 3. |
- Maury, O., et al.
(författare)
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From shared socio-economic pathways (SSPs) to oceanic system pathways (OSPs) : Building policy-relevant scenarios for global oceanic ecosystems and fisheries
- 2017
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 45, s. 203-216
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for developing policy-relevant future scenarios of biodiversity and ecosystem services. This paper is a milestone toward this aim focusing on open ocean fisheries. We develop five contrasting Oceanic System Pathways (OSPs), based on the existing five archetypal worlds of Shared Socioeconomic Pathways (SSPs) developed for climate change research (e.g., Nakicenovic et al., 2014 and Riahi et al., 2016). First, we specify the boundaries of the oceanic social-ecological system under focus. Second, the two major driving forces of oceanic social-ecological systems are identified in each of three domains, viz., economy, management and governance. For each OSP (OSP1 sustainability first, OSP2 conventional trends, OSP3 dislocation, OSP4 global elite and inequality, OSP5 high tech and market), a storyline is outlined describing the evolution of the driving forces with the corresponding SSP. Finally, we compare the different pathways of oceanic social-ecological systems by projecting them in the two-dimensional spaces defined by the driving forces, in each of the economy, management and governance domains. We expect that the OSPs will serve as a common basis for future model based scenario studies in the context of the Intergovernmental Panel on Climate Change (IPCC) and the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES).
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