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Introduction: First-line oxygenation strategy in patients with acute hypoxaemic respiratory failure consists in standard oxygen or high-flow nasal oxygen therapy. Clinical practice guidelines suggest the use of high-flow nasal oxygen rather than standard oxygen. However, findings remain contradictory with a low level of certainty. We hypothesise that compared with standard oxygen, high-flow nasal oxygen may reduce mortality in patients with acute hypoxaemic respiratory failure., Method and Analysis: The Standard Oxygen versus High-flow nasal Oxygen-trial is an investigator-initiated, multicentre, open-label, randomised controlled trial comparing high-flow nasal oxygen versus standard oxygen in patients admitted to an intensive care unit (ICU) for acute respiratory failure with moderate-to-severe hypoxaemia. 1110 patients will be randomly assigned to one of the two groups with a ratio of 1:1. The primary outcome is the number of patients who died 28 days after randomisation. Secondary outcomes include comfort, dyspnoea and oxygenation 1 hour after treatment initiation, the number of patients intubated at day 28, mortality in ICU, in hospital and until day 90, and complications during ICU stay., Ethics and Dissemination: The study has been approved by the central Ethics Committee 'Sud Méditerranée III' (2020-07-05) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04468126., Competing Interests: Competing interests: J-PF reports grants from the French Ministry of Health; personal fees for lectures, travel expense coverage to attend scientific meetings, grant for randomised clinical trial from Fisher and Paykel Healthcare; personal fees as member of a scientific board and travel expense coverage to attend scientific meetings from SOS Oxygène outside this work. RC reports grants from the European Respiratory Society and the French Intensive Care Society, and travel expense coverage to attend scientific meetings from Fisher and Paykel Healthcare and MSD. SE discloses consultancies from Aerogen, research support, speaker fees and travel support from Aerogen and Fisher & Paykel Healthcare, research support from Open AI. AD reports grants from the French Ministry of Health, Assistance publique – Hôpitaux de Paris, Lungpacer, Respinor, consulting fees from Respinor, Lungpacer, Lowenstein, Tribunal administratif de Cergy, Liberate Medical, payment or honoraria for lectures, presentations from Fisher & Paykel, Baxter, Getinge, Astra, Agence Européenne Informatique, Mindray, support for attending meetings and/or travel from Lungpacer, outside the submitted work. GCarteaux reports personal fees from Air Liquide Medical System, GE Healthcare, Dräger, Fisher and Paykel, Medtronic and Löwenstein, outside the submitted work. FB reports consulting fees from Löwenstein Medical and Air Liquid Medical Systems and research support from Covidien and GE Healthcare outside this work. J-CR reports grant from Hamilton medical and travel expense coverage to attend scientific meetings from GILEAD and Pfizer. GH has received personal fees for lectures, travel expense coverage to attend scientific meetings from Fisher and Paykel Healthcare. AWT reports travel expanse coverage to attend scientific meetings and payment for lectures from Fisher and Paykel Healthcare, Covidien, Maquet-Getinge, Dräger Medical, General Electric Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Plant root development depends on signaling pathways responding to external and internal signals. In this study we demonstrate the involvement of the Lotus japonicus LjNPF4.6 gene in the ABA and nitrate root responding pathways. LjNPF4.6 expression in roots is induced by external application of both nitrate and ABA. LjNPF4.6 promoter activity is spatially localized in epidermal cell layer and vascular bundle structures with the latter pattern being controlled by externally applied ABA. LjNPF4.6 cRNA injection achieves both nitrate and ABA uptake in Xenopus laevis oocytes and the analyses of L. japonicus knock-out insertion mutants confirmed the role played by LjNPF4.6 in root nitrate uptake. The phenotypic characterization of the Ljnpf4.6 plants indicates the role played by LjNPF4.6 in the root program development in response to exogenously applied nitrate and ABA. Based on the presented data, the mode of action of this transporter is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Soil calcium carbonate (CaCO 3 ) impacts plant mineral nutrition far beyond Fe metabolism, imposing constraints for crop growth and quality in calcareous agrosystems. Our knowledge on plant strategies to tolerate CaCO 3 effects mainly refers to Fe acquisition. This review provides an update on plant cellular and molecular mechanisms recently described to counteract the negative effects of CaCO 3 in soils, as well as recent efforts to identify genetic bases involved in CaCO 3 tolerance from natural populations, that could be exploited to breed CaCO 3 -tolerant crops. Finally, we review the impact of environmental factors (soil water content, air CO 2 , and temperature) affecting soil CaCO 3 equilibrium and plant tolerance to calcareous soils, and we propose strategies for improvement in the context of climate change., Competing Interests: Declaration of interests The authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite evidence associating inflammatory biomarkers with worse outcomes in hospitalized adults with COVID-19, trials of immunomodulatory therapies have met with mixed results, likely due in part to biological heterogeneity of participants. Latent class analysis (LCA) of clinical and protein biomarker data has identified two subtypes of non-COVID acute respiratory distress syndrome (ARDS) with different clinical outcomes and treatment responses. We studied biological heterogeneity and clinical outcomes in a multi-institutional platform randomized controlled trial of adults with severe COVID-19 hypoxemic respiratory failure (I-SPY COVID)., Methods: Clinical and plasma protein biomarker data were analyzed from 400 trial participants enrolled from September 2020 until October 2021 with severe COVID-19 requiring ≥ 6 L/min supplemental oxygen. Seventeen hypothesis-directed protein biomarkers were measured at enrollment using multiplex Luminex panels or single analyte enzyme linked immunoassay methods (ELISA). Biomarkers and clinical variables were used to test for latent subtypes and longitudinal biomarker changes by subtype were explored. A validated parsimonious model using interleukin-8, bicarbonate, and protein C was used for comparison with non-COVID hyper- and hypo-inflammatory ARDS subtypes., Results: Average participant age was 60 ± 14 years; 67% were male, and 28-day mortality was 25%. At trial enrollment, 85% of participants required high flow oxygen or non-invasive ventilation, and 97% were receiving dexamethasone. Several biomarkers of inflammation (IL-6, IL-8, IL-10, sTNFR-1, TREM-1), epithelial injury (sRAGE), and endothelial injury (Ang-1, thrombomodulin) were associated with 28- and 60-day mortality. Two latent subtypes were identified. Subtype 2 (27% of participants) was characterized by persistent derangements in biomarkers of inflammation, endothelial and epithelial injury, and disordered coagulation and had twice the mortality rate compared with Subtype 1. Only one person was classified as hyper-inflammatory using the previously validated non-COVID ARDS model., Conclusions: We discovered evidence of two novel biological subtypes of severe COVID-19 with significantly different clinical outcomes. These subtypes differed from previously established hyper- and hypo-inflammatory non-COVID subtypes of ARDS. Biological heterogeneity may explain inconsistent findings from trials of hospitalized patients with COVID-19 and guide treatment approaches., (© 2024. The Author(s).)

Diatoms are a highly successful group of phytoplankton, well adapted also to oligotrophic environments and capable of handling nutrient fluctuations in the ocean, particularly nitrate. The presence of a large vacuole is an important trait contributing to their adaptive features. It confers diatoms the ability to accumulate and store nutrients, such as nitrate, when they are abundant outside and then to reallocate them into the cytosol to meet deficiencies, in a process called luxury uptake. The molecular mechanisms that regulate these nitrate fluxes are still not known in diatoms. In this work, we provide new insights into the function of Phaeodactylum tricornutum NPF1, a putative low-affinity nitrate transporter. To accomplish this, we generated overexpressing strains and CRISPR/Cas9 loss-of-function mutants. Microscopy observations confirmed predictions that PtNPF1 is localized on the vacuole membrane. Furthermore, functional characterizations performed on knock-out mutants revealed a transient growth delay phenotype linked to altered nitrate uptake. Together, these results allowed us to hypothesize that PtNPF1 is presumably involved in modulating intracellular nitrogen fluxes, managing intracellular nutrient availability. This ability might allow diatoms to fine-tune the assimilation, storage and reallocation of nitrate, conferring them a strong advantage in oligotrophic environments., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Purpose: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS., Methods: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO 2  ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography., Results: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83])., Conclusions: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge., (© 2023. The Author(s).)

Data from functional trait databases have been increasingly used to address questions related to plant diversity and trait-environment relationships. However, such databases provide intraspecific data that combine individual records obtained from distinct populations at different sites and, hence, environmental conditions. This prevents distinguishing sources of variation (e.g., genetic-based variation vs. phenotypic plasticity), a necessary condition to test for adaptive processes and other determinants of plant phenotypic diversity. Consequently, individual traits measured under common growing conditions and encompassing within-species variation across the occupied geographic range have the potential to leverage trait databases with valuable data for functional and evolutionary ecology. Here, we recorded 16 functional traits and leaf hyperspectral reflectance (NIRS) data for 721 widely distributed Arabidopsis thaliana natural accessions grown in a common garden experiment. These data records, together with meteorological variables obtained during the experiment, were assembled to create the AraDiv dataset. AraDiv is a comprehensive dataset of A. thaliana's intraspecific variability that can be explored to address questions at the interface of genetics and ecology., (© 2023. The Author(s).)

Nutrient sensing and signaling are essential for adjusting growth and development to available resources. Deprivation of the essential mineral phosphorus (P) inhibits root growth. 1 The molecular processes that sense P limitation to trigger early root growth inhibition are not known yet. Target of rapamycin (TOR) kinase is a central regulatory hub in eukaryotes to adapt growth to internal and external nutritional cues. 2 , 3 How nutritional signals are transduced to TOR to control plant growth remains unclear. Here, we identify Arabidopsis-root-specific kinase 1 (ARSK1), which attenuates initial root growth inhibition in response to P limitation. We demonstrate that ARSK1 phosphorylates and stabilizes the regulatory-associated protein of TOR 1B (RAPTOR1B), a component of the TOR complex 1, to adjust root growth to P availability. These findings uncover signaling components acting upstream of TOR to balance growth to P availability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: HDV, a satellite of HBV, is responsible for the most severe form of human viral hepatitis, for which curative therapy is still awaited. Both HBV and HDV use the hepatic transporter of bile acids (ie, Na+-taurocholate cotransporting polypeptide) to enter hepatocytes. We have previously shown that ligands of the farnesoid-X-receptor alpha (FXR), a master regulator of bile acids metabolism, inhibit HBV replication. Here we asked whether FXR ligands can also control HDV infection., Approach and Results: In vitro HDV monoinfections or HDV/HBV coinfections and superinfections were performed in differentiated HepaRG cells (dHepaRG) and primary human hepatocytes. Following treatment with FXR ligands, HDV RNAs and antigens were analyzed by RT-qPCR, northern blot, immunofluorescence, and western blot. Virus secretion was studied by RNA quantification in supernatants, and the infectivity of secreted HDV particles was measured by reinfection of naive HuH7.5-Na+-taurocholate cotransporting polypeptide cells. In HDV/HBV superinfection models, a 10-day treatment with FXR ligand GW4064 decreased intracellular HDV RNAs by 60% and 40% in dHepaRG cells and primary human hepatocytes, respectively. Both HDV genomic and antigenomic RNAs were affected by treatment, which also reduced the amount of intracellular delta antigen. This antiviral effect was also observed in HDV monoinfected dHepaRG cells, abolished by FXR loss of function, and reproduced with other FXR ligands. In HBV/HDV coinfected dHepaRG cells, HDV secretion was decreased by 60% and virion-specific infectivity by >95%., Conclusions: FXR ligands both inhibit directly (ie, independently of anti-HBV activity) and indirectly (ie, dependently of anti-HBV activity) the replication, secretion, and infectivity of HDV. The overall anti-HDV activity was superior to that obtained with interferon-α, highlighting the therapeutic potential of FXR ligands in HDV-infected patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)