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Background: Natural populations of Arabidopsis thaliana exhibit phenotypic variations in specific environments and growth conditions. However, this variation has not been explored after seed osmopriming treatments. The natural variation in biomass production and root system architecture (RSA) was investigated across the Arabidopsis thaliana core collection in response to the pre-sawing seed treatments by osmopriming, with and without melatonin (Mel). The goal was to identify and characterize physiologically contrasting ecotypes., Results: Variability in RSA parameters in response to PEG-6000 seed osmopriming with and without Mel was observed across Arabidopsis thaliana ecotypes with especially positive impact of Mel addition under both control and 100 mM NaCl stress conditions. Two ecotypes, Can-0 and Kn-0, exhibited contrasted root phenotypes: seed osmopriming with and without Mel reduced the root growth of Can-0 plants while enhancing it in Kn-0 ones under both control and salt stress conditions. To understand the stress responses in these two ecotypes, main stress markers as well as physiological analyses were assessed in shoots and roots. Although the effect of Mel addition was evident in both ecotypes, its protective effect was more pronounced in Kn-0. Antioxidant enzymes were induced by osmopriming with Mel in both ecotypes, but Kn-0 was characterized by a higher responsiveness, especially in the activities of peroxidases in roots. Kn-0 plants experienced lower oxidative stress, and salt-induced ROS accumulation was reduced by osmopriming with Mel. In contrast, Can-0 exhibited lower enzyme activities but the accumulation of proline in its organs was particularly high. In both ecotypes, a greater response of antioxidant enzymes and proline accumulation was observed compared to mechanisms involving the reduction of Na + content and prevention of K + efflux., Conclusions: In contrast to Can-0, Kn-0 plants grown from seeds osmoprimed with and without Mel displayed a lower root sensitivity to NaCl-induced oxidative stress. The opposite root growth patterns, enhanced by osmopriming treatments might result from different protective mechanisms employed by these two ecotypes which in turn result from adaptive strategies proper to specific habitats from which Can-0 and Kn-0 originate. The isolation of contrasting phenotypes paves the way for the identification of genetic factors affecting osmopriming efficiency., (© 2024. The Author(s).)

Background: There is no standard definition of respiratory-related hospitalisation, a common end-point in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events., Methods: An algorithm for respiratory-related hospitalisation was developed through a literature review of IPF clinical trials with respiratory-related hospitalisation as an end-point. Experts reviewed the algorithm until a consensus was reached. The algorithm was validated using data from the phase 3 ISABELA trials (clinicaltrials.gov identifiers NCT03711162 and NCT03733444), by assessing concordance between nonadjudicated, investigator-defined, respiratory-related hospitalisations and those defined by the adjudication committee using the algorithm., Results: The algorithm classifies respiratory-related hospitalisation according to cause: extraparenchymal (worsening respiratory symptoms due to left heart failure, volume overload, pulmonary embolism, pneumothorax or trauma); other (respiratory tract infection, right heart failure or exacerbation of COPD); "definite" acute exacerbation of IPF (AEIPF) (worsening respiratory symptoms within 1 month, with radiological or histological evidence of diffuse alveolar damage); or "suspected" AEIPF (as for "definite" AEIPF, but with no radiological or histological evidence of diffuse alveolar damage). Exacerbations ("definite" or "suspected") with identified triggers (infective, post-procedural or traumatic, drug toxicity- or aspiration-related) are classed as "known AEIPF"; "idiopathic AEIPF" refers to exacerbations with no identified trigger. In the ISABELA programme, there was 94% concordance between investigator- and adjudication committee-determined causes of respiratory-related hospitalisation., Conclusion: The algorithm could help to ensure consistency in the reporting of respiratory-related hospitalisation in IPF trials, optimising its utility as an end-point., Competing Interests: Conflict of interest: P. Ford and N. Prasad are former employees of, and have received warrants from, Galapagos. Conflict of interest: M. Kreuter reports grants and personal fees from Galapagos during the conduct of the study, and grants and personal fees from Boehringer Ingelheim and Roche outside the submitted work. Conflict of interest: K.K. Brown reports support from the National Heart, Lung, and Blood Institute; participation on a Scientific Advisory Board/work as an external science advisor for Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, DevPro Biopharma, Eleven P15, Galapagos, Galecto, Huitai Biomedicine, Open Source Imaging, Pliant, RedxPharma and Sanofi; participation on a data monitoring committee for Biogen and Humanetics; and work in a leadership or fiduciary role for the Fleischner Society and the Open Source Imaging Consortium. Conflict of interest: W.A. Wuyts reports no personal fees; the University Hospitals Leuven received consultancy fees from Galapagos during the conduct of the study, and grants from Boehringer Ingelheim and Roche outside the submitted work. Conflict of interest: M. Wijsenbeek reports no personal fees; the Erasmus MC received consultancy fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Galapagos, Galecto, Hoffmann-La Roche, Horizon Therapeutics, Kinevant Sciences, Molecure, NeRRe Therapeutics, Novartis, PureTech Health, Thyron and Vicore; and grants from AstraZeneca/Daiichi Sankyo, Boehringer Ingelheim and Hoffmann-La Roche outside the submitted work. The Erasmus MC received speaker fees from Boehringer Ingelheim, CSL Behring and Hoffmann-La Roche outside the submitted work. Conflict of interest: D. Israël-Biet reports speaker and advisory board fees from Boehringer Ingelheim. Conflict of interest: R. Hubbard reports consulting fees from Galapagos. Conflict of interest: S.D. Nathan reports consulting fees from Bellerophon, Boehringer Ingelheim, Galapagos, Roche-Genentech and United Therapeutics. He is on the speakers’ bureau for Boehringer Ingelheim, Roche-Genentech and United Therapeutics. Conflict of interest: H. Nunes reports consulting fees from Galapagos during the conduct of the study, and consulting fees from Boehringer Ingelheim and Roche-Genentech. Conflict of interest: B. Penninckx is a former consultant to Galapagos. Conflict of interest: I. Seghers is a former employee of Galapagos. Conflict of interest: N. Verbruggen is an employee of Galapagos. Conflict of interest: P. Spagnolo reports consulting fees from Behring, Chiesi, Galapagos (during the conduct of this study), Glycocore, Lupin, Novartis, Pieris and PPM services, and institutional grants from Boehringer Ingelheim, PPM services and Roche outside the submitted work. Conflict of interest: N. Hirani reports no personal fees; the University of Edinburgh received fees from Boehringer Ingelheim, Galapagos, Guidepoint Global and Roche for consultancy and advisory work on behalf of Dr Hirani. The University of Edinburgh and NHS Lothian R&D have received grants and donations from Boehringer Ingelheim, Galecto, Indalo, Roche and UCB on behalf of Dr Hirani. No consultancies or grants are directly related to the submitted work. Conflict of interest: J. Behr reports personal fees from Galapagos during the conduct of the study, and consultation or advisory fees from AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pliant, Roche and Sanofi/Genzyme; funding or grants from Boehringer Ingelheim; speaking and lecture fees from AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Ferrer, Novartis, Pliant, Roche and Sanofi/Genzyme; and travel reimbursement from Boehringer Ingelheim, Ferrer and Roche outside the submitted work. Conflict of interest: R.J. Kaner reports personal fees from Galapagos during the conduct of the study, and grants from Afferent, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi Pillar, CSL Behring, Genentech, National Institutes of Health, Pulmonary Fibrosis Foundation, Respivant and Toray, and personal fees from Boehringer Ingelheim, Genentech, Gilead, Medimmune, The France Foundation and United Therapeutics outside the submitted work. Conflict of interest: T.M. Maher, via his institution, has received industry-academic funding from AstraZeneca and GlaxoSmithKline R&D, and consultation or advisory fees from AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Fibrogen, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant, Roche, Trevi and Veracyte., (Copyright ©The authors 2024.)