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Journal articleMolyneaux PL, Mogulkoc N, Gunen H, et al., 2026,
Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial.
, JAMAIMPORTANCE: For patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed. OBJECTIVE: To determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough. DESIGN, SETTING, AND PARTICIPANTS: In this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025. INTERVENTION: Patients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6. RESULTS: Of the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2%
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Journal articleLedesma Amaro R, 2026,
Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity
, Nature Communications, Vol: 17, ISSN: 2041-1723Heterogeneity within clonal cell populations remains a critical bottleneck within bioprocess engineering, notably by undermining bioproduction yields. Efforts to mitigate its impact have, however, been hampered by technological difficulties quantifying metabolism at the single-cell level. Here, we propose a framework based on single-cell biosensor analysis that enables robust characterisation of cell's metabolic states, leveraging it to detect and isolate isogeneic heterogeneity in response to environmental perturbations and within microbial cell factories. We identify acute and gradual glucose depletion to induce differentiation of metabolically distinct subpopulations and reveal these subpopulations to exhibit differential production capabilities, with lower intracellular pH subpopulations exhibiting enhanced product accumulation within violacein-producing strains but reduced yields within lycopene-producing strains. Lastly, we highlight galactose cultivation as a method to modulate subpopulation dynamics towards higher-producing lycopene phenotypes. Altogether, our research provides insights into subpopulation differentiation and establishes promising avenues for the engineering of more robust and higher-producing strains.
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Journal articleYousefi N, Tao H, Anthony DB, et al., 2026,
Scale matters: a perspective on structural hierarchical carbon fibre composites incorporating carbon nanotubes
, Composites Science and Technology, ISSN: 0266-3538Composites have long played a vital role in material science due to their lightweight, stiff, strong, and durable construction. Composites consist of at least two complementary materials, typically comprising reinforcing elements, prominently carbon or glass fibres, held in place by a surrounding polymer matrix. Conventional fibre composites already display a structural hierarchy from fibres within tows, to plies, to laminates forming large-scale structures. The term “hierarchical composites” specifically refers to materials that integrate reinforcements spanning additional length scales, down to the molecular range, most notably nanoscale reinforcements that complement microscale fibres. Natural structural materials rely extensively on hierarchical motifs to maximise performance, though using constituents limited by abundance and ambient aqueous processing. Technical hierarchical composites are broadly inspired by natural multiscale systems, sometimes implementing specific mechanisms from nature in new material classes. In hierarchical composites, the largest reinforcement, fibres, dominate in-plane mechanical properties. In contrast, nanoscale reinforcements may address matrix-dominated responses by, for example, improving shear properties that control stress transfer and kink band initiation, introducing additional toughening mechanisms to limit debonding or delamination, and providing direct reinforcement, particularly through-thickness. Nanomaterials can provide other benefits, such as improved fatigue life, acoustic damping, and solvent/fire resistance. The addition of nanomaterials may also imbue composites with multifunctionality, obviating other constituents or components and reducing system weight. We critically discuss the progress in developing hierarchical fibre reinforced carbon nanotube composites over the past decade and provide insight into manufacturing and their structural and functional performance.
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Journal articleHowlett P, Durairaj A, Lesosky M, et al., 2026,
The diagnostic accuracy of chest Xray screening for silicosis: a systematic review, meta-analysis and modelling study
, Occupational and Environmental Medicine, ISSN: 1351-0711Objectives: Chest Xray (CXR) is widely used for silicosis diagnosis, despite concerns egarding sensitivity. We investigated the diagnostic accuracy of CXR for silicosis screening compared to computed tomography (CT), high-resolution CT (HRCT) and autopsy, and modelled the relationship between CXR sensitivity and disease severity. Methods: Medline, Embase, Scopus, and Web of Science databases were searched on 2nd July 2024 (Prospero registration: CRD42024513830). Meta-analyses were performed by reference standard and at increasing reference test severity cut-offs. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool assessed risk of bias. In scenarios of fixed and relative sensitivity, according to disease severity, we estimated missed silicosis cases and the number needed to screen (NNS) in hypothetical populations of low (5%), medium (15%) and high (30%) silicosis prevalence. Results: Twenty studies included 2156 participants and 1105 silicosis cases. CXR had moderate sensitivity (0.76; 95% confidence interval (CI): 0.63-0.86, I2=84%) and high specificity (0.89, 95% CI: 0.77-0.95, I2=57%) compared to HRCT in 12 studies, and low sensitivity (0.50, 95% CI: 0.45-0.55, I2=0%) and high specificity (0.91, 95% CI: 0.87-0.93, I2=20%) compared to autopsy in two studies. CXR sensitivity increased with higher reference test severity cut-offs. Clinically relevant numbers of cases were missed in fixed and relative sensitivity scenarios; increased prevalence and less severe disease resulted in more missed cases and a lower NNS.Conclusions: Silicosis severity and reference test type both plausibly influence CXR sensitivity. Assuming either fixed or relative sensitivity results in missed silicosis cases. Judicious HRCT screening is likely to improve case detection.
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Journal articleChen H, Peng H, Ellis T, et al., 2026,
Programmable cell–cell adhesion in synthetic yeast communities for improved bioproduction
, Nature Chemical Biology, ISSN: 1552-4450In multicellular systems, engineering-controlled cell–cell adhesion and metabolic interdependence are vital for developing complex functionalities. This study introduces a yeast synthetic toolbox for modular cell–cell adhesion and cocultures, aiming to overcome the limitations of existing approaches that lack genetic specificity and control. First, a model yeast strain 007Δ is created with seven main flocculation and agglutination genes removed, providing a clean background for synthetic adhesion systems. Then, three distinct adhesion pair systems—Strategy 1, Strategy 2.1 and Strategy 2.2—are established involving yeast flocculation and agglutination proteins and yeast surface display systems. In addition, a quantitative assessment is conducted on the adhesive specificity and strength, alongside the capability of synthetic adhesion to generate patterns. Finally, we successfully demonstrate enhanced bioproduction of the high-value food antioxidant, resveratrol, utilizing synthetic cocultures coupled with cell adhesion systems. We anticipate that this toolkit will emerge as a valuable resource for diverse applications in synthetic biology and biomanufacturing.
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Journal articleMcKenzie J, Carter C, Jackson MM, et al., 2026,
Mechanisms driving immunopathogenesis of viral exacerbations in chronic respiratory disease.
, ThoraxBACKGROUND: Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respiratory viruses as predominant triggers, though the underlying immunopathogenic mechanisms remain poorly understood. NARRATIVE: This review synthesises current knowledge on the interplay between viral pathogens at the airway epithelial barrier, including structural and immunological mechanisms that may dysregulate antiviral immunity in chronic respiratory diseases. Furthermore, we discuss how perturbations in the respiratory microbiome, characterised by reduced microbial diversity, can modulate host antiviral immune defences. CONCLUSIONS: Collectively, these interconnected factors create a permissive environment predisposing to viral infection and exacerbations in chronic respiratory diseases. Understanding the complex interactions between airway structure, interferon-mediated antiviral responses, inflammation and microbiota is essential for developing targeted therapies to effectively manage virus-induced exacerbations and reduce disease burden.
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Journal articleXu C, Wang Z, Sun L, et al., 2026,
Sustainable bioprocess for D-chiro-inositol production via metabolic engineering of <i>Saccharomyces cerevisiae</i>
, CHEMICAL ENGINEERING JOURNAL, Vol: 527, ISSN: 1385-8947 -
Journal articleNarayana JK, Chotirmall SH, 2026,
Reply: Methodological clarifications of AI-powered research trend analytics in bronchiectasis.
, Eur Respir J, Vol: 67 -
Journal articleMartin AK, Mercier O, Fritz AV, et al., 2026,
ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part II: Intraoperative Considerations
, JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol: 45, Pages: e35-e62, ISSN: 1053-2498- Cite
- Citations: 10
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Journal articleIdrees S, Chen H, Sadaf T, et al., 2026,
Multi-omics to study chronic respiratory diseases and viral infections.
, Eur Respir Rev, Vol: 35Despite recent advances, the underlying mechanisms of the development and progression of many chronic respiratory diseases remain to be elucidated. Factors such as heterogeneity and complexity of human diseases and difficulty interpreting large datasets hinder research into chronic respiratory diseases. Omics assesses the changes in specific biological entities, such as mRNA expression, epigenetics/epigenomics, genomics, proteomics, metagenomics and metabolomics, and provides valuable insights into the roles of these processes in chronic respiratory diseases. High-throughput omics at bulk, single-cell and spatial levels empower the exploration of disease-related changes through untargeted data-driven statistical methods. Multi-omics is the exploration and integration of multiple biological processes, which compared to a single-omics, can provide a substantially greater and more holistic overview of the pathogenic mechanisms that underpin complex diseases. Multi-omics analysis can comprehensively characterise the mechanisms that drive chronic respiratory diseases, capturing unique biological signatures and cellular interactions at different omics levels. Use of these methods has begun to identify key factors and biomarkers in chronic respiratory diseases. Here, we review current omics approaches and highlight recent advances in respiratory research achieved using multi-omics and integrative methods. Our review provides a valuable resource for researchers and clinicians in this area.
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