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- Peterson, Q. P., et al.
(författare)
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A method for the generation of human stem cell-derived alpha cells
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The generation of pancreatic cell types from renewable cell sources holds promise for cell replacement therapies for diabetes. Although most effort has focused on generating pancreatic beta cells, considerable evidence indicates that glucagon secreting alpha cells are critically involved in disease progression and proper glucose control. Here we report on the generation of stem cell-derived human pancreatic alpha (SC-alpha) cells from pluripotent stem cells via a transient pre-alpha cell intermediate. These pre-alpha cells exhibit a transcriptional profile similar to mature alpha cells and although they produce proinsulin protein, they do not secrete significant amounts of processed insulin. Compound screening identified a protein kinase c activator that promotes maturation of pre-alpha cells into SC-alpha cells. The resulting SC-alpha cells do not express insulin, share an ultrastructure similar to cadaveric alpha cells, express and secrete glucagon in response to glucose and some glucagon secretagogues, and elevate blood glucose upon transplantation in mice. Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.
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- Rajamani, Arvind, et al.
(författare)
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Criteria, Processes, and Determination of Competence in Basic Critical Care Echocardiography Training A Delphi Process Consensus Statement by the Learning Ultrasound in Critical Care (LUCC) Initiative
- 2022
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Ingår i: Chest. - : ELSEVIER. - 0012-3692 .- 1931-3543. ; 161:2, s. 492-503
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: With the paucity of high-quality studies on longitudinal basic critical care echocardiography (BCCE) training, expert opinion guidelines have guided BCCE competence educational standards and processes. However, existing guidelines lack precise detail due to methodological flaws during guideline development. RESEARCH QUESTIONS: To formulate methodologically robust guidelines on BCCE training using evidence and expert opinion, detailing specific criteria for every step, we conducted a modified Delphi process using the principles of the validated AGREE-II tool. Based on systematic reviews, the following domains were chosen: components of a longitudinal BCCE curriculum; pass-grade criteria for image-acquisition and image-interpretation; and formative/summative assessment and final competence processes. STUDY DESIGN AND METHODS: Between April 2020 and May 2021, a total of 21 BCCE experts participated in four rounds. Rounds 1 and 2 used five web-based questionnaires, including branching-logic software for directed questions to individual panelists. In round 3 (videoconference), the panel finalized the recommendations by vote. During the journal peer-review process, Round 4 was conducted as Web-based questionnaires. Following each round, the agreement threshold for each item was determined as >= 80% for item inclusion and <= 30% for item exclusion. RESULTS: Following rounds 1 and 2, agreement was reached on 62 of 114 items. To the 49 unresolved items, 12 additional items were added in round 3, with 56 reaching agreement and five items remaining unresolved. There was agreement that longitudinal BCCE training must include introductory training, mentored formative training, summative assessment for competence, and final cognitive assessment. Items requiring multiple rounds included two-dimensional views, Doppler, cardiac output, M-mode measurement, minimum scan numbers, and pass-grade criteria. Regarding objective criteria for image-acquisition and image-interpretation quality, the panel agreed on maintaining the same criteria for formative and summative assessment, to categorize BCCE findings as major vs minor and a standardized approach to errors, criteria for readiness for summative assessment, and supervisory options. INTERPRETATION: In conclusion, this expert consensus statement presents comprehensive evidence-based recommendations on longitudinal BCCE training. However, these recommendations require prospective validation.
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- Rajamani, Arvind, et al.
(författare)
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Response
- 2022
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Ingår i: Chest. - : ELSEVIER. - 0012-3692 .- 1931-3543. ; 161:6, s. E401-E402
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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