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. 2021 Jul 30;11:15511. doi: 10.1038/s41598-021-94798-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Inner fluid reservoir areas are more sensitive to categorize between healthy and CF responses after FSK-incubation. Both CRA and IFRA areas were studied in WT and CF subjects after 60 min following FSK-incubation. Each CF subject is represented by a different color. All CF nasospheroids were grown under condition 1. (a) CRA and IFRA DMSO CF values (t = 60) are represented by a dotted line. CF1 and CF2 unrelated patients share the same genotype (F508del/2183AA>G) but show significant different FSK responses (****p < 0.0001) in IFRA analysis. Columns of CF patients represent mean FR values. Bars represent SEM. AUC values after IFRA (b) and CRA (c) assessment were determined by GraphPad Prism (baseline Y = 0) at t = 60 min. Dots represent mean AUC values from FSK-incubated nasospheroids. Empty squares represent mean AUC values of VX-770 + VX-809-treated nasospheroids. Inverted triangles show mean AUC values from VX-770 + VX-661-treated nasospheroids. Bars represent standard deviation (SD). Significant differences (p < 0.05) within VX-treated and FSK-treated nasospheroids are shown. VX-incubation was always combined with FSK, Amiloride and IBMX. Graphic created with GraphPad Prism version 6³³.