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Journal articleGreenland JR, Perch M, Halloran K, et al., 2026,
Considerations for Endpoints in Lung Transplant Clinical Trials: An ISHLT Consensus Statement.
, J Heart Lung Transplant, Vol: 45, Pages: e104-e128Clinical trials in lung transplantation have been hindered by a lack of clarity on the formulation and significance of endpoints for evaluating therapeutic efficacy. To address this challenge, a multidisciplinary working group from the International Society for Heart and Lung Transplantation developed consensus recommendations on endpoints beyond mortality. These endpoints include primary graft dysfunction (PGD), chronic lung allograft dysfunction (CLAD), acute cellular rejection (ACR), antibody-mediated rejection (AMR), immunosuppression-related complications, patient-reported outcomes (PROs), and pediatric-specific considerations. For each endpoint, a subgroup reviewed measurement best practices, assessed links to clinical benefit, and evaluated the evidence supporting their utility in clinical trial settings. Consensus was established through a Delphi process involving three rounds of voting. This document provides practical guidance for operationalizing these endpoints and outlines their optimal use in clinical trials. By standardizing trial design, these recommendations aim to accelerate the development of urgently needed therapies to improve lung transplantation outcomes.
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Journal articleGreenland JR, Perch M, Halloran K, et al., 2026,
Considerations for Endpoints in Lung Transplant Clinical Trials: Perspective on the ISHLT Consensus Statement.
, J Heart Lung Transplant, Vol: 45, Pages: 168-171 -
Journal articleShah A, 2026,
CFTR modulators partially restore the epithelial interferome in Aspergillus infection to improve clinical outcome
, EBioMedicine, ISSN: 2352-3964BackgroundThe impact of CFTR modulator therapy on host immunity and outcomes in people with Cystic Fibrosis (CF)-related Aspergillus lung disease is poorly defined. We aimed to characterise fungal-relevant clinical outcomes post-CFTR modulators and assess effects on the Aspergillus-dependent Type I/III interferome.MethodsBiomarkers of Aspergillus-related lung disease (Aspergillus-specific IgE/IgG), anti-fungal and corticosteroid therapy were analysed in a retrospective cohort of people with CF pre and post Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy. Homozygous F508del (CF) and CFTR TALEN-corrected bronchial epithelial cells (BECs) were challenged with Aspergillus conidia and hyphae in the presence or absence of ETI CFTR modulator therapy with bulk RNA transcriptomics and RT-PCR used to analyse Type I/III interferon genes. Effects of exogenous type I and III interferons on CF-neutrophil antifungal effector function was further characterised. FindingsCFTR modulator (ETI) therapy was associated with a significant reduction in Aspergillus biomarkers alongside use of corticosteroid and anti-fungal therapy. In vitro Aspergillus stimulation enriched the Type I/III interferome in CFTR-corrected BECs compared to CF BECs, with ETI therapy partially restoring type I/III interferon gene expression in CF BECs. Administration of exogenous IFN𝝀1 increased anti-fungal killing in CF neutrophils without increased reactive-oxygen species or neutrophil extracellular trap production.InterpretationCFTR modulators have led to improved clinical outcomes in CF related Aspergillus-related lung disease potentially due to partial restoration of the host antifungal epithelial type I/III interferon response. Exogenous IFNλ1 further improved antifungal killing capacity of CF-neutrophils presenting a plausible future therapeutic strategy.Funding: This study was funded by the Cystic Fibrosis Trust (SRC015).
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Journal articleShirvanyan A, Primavera A, Guaragnella N, et al., 2026,
Thiol groups are determinant for overcoming acetic acid and pH stress in wine and beer fermentation-derived Saccharomyces cerevisiae strains
, FEMS Yeast Research, Vol: 26, ISSN: 1567-1356Acetic acid (AA), a natural by-product of ethanol fermentation in yeast cells, is widely present in lignocellulosic hydrolysate as a fermentation inhibitor. Thus, gaining insight into the molecular mechanisms of AA tolerance in yeast is particularly relevant for industrial applications. This study investigates the response to AA stress in two Saccharomyces cerevisiae strains (ATCC 9804 and ATCC 13007) during different metabolic states (fermentation, respiro-fermentation, and respiration) and external pH levels (3․0 and 4.5). The results show that AA reduces the viability of both strains in a dosage-dependent manner. Moreover, ATCC 13007 is more sensitive to AA stress compared to ATCC 9804. Respiratory metabolism and higher pH correlate with better resistance to AA stress. Catalase activity was observed to increase by 1.5–6-fold under AA stress conditions, in accordance with changes in yeast thiol group content and growth. The influence of AA stress is reactive oxygen species-dependent, and redox balance regulation was found to increase the robustness of S. cerevisiae ATCC 13007 to AA by 2-fold. The study reveals valuable insights into yeast adaptation to stress conditions, contributing to the development of robust yeast strain construction for high-yield biomass and chemicals production.
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Journal articleHemmings S, Varaden D, Barnes J, et al., 2026,
Diversity analysis of indoor and outdoor fungal bioaerosols in UK households: a longitudinal study
, The Lancet Microbe, ISSN: 2666-5247BackgroundProlonged exposure to indoor fungal bioaerosols is a recognised risk factor for respiratory illness, particularly in damp and poorly ventilated housing. However, the diversity and seasonal variability of these communities are poorly understood. This study as part of WellHome, aimed to characterise the composition, diversity, and temporal dynamics of indoor fungal bioaerosols in urban UK homes compared with outdoor air, to inform future exposure baselines and policy development.MethodsIn this prospective, community-based observational study, 118 households were recruited across West London, UK, via community networks and partner organisations, prioritising families with children aged 5–17 years with asthma or allergies from diverse socioeconomic backgrounds. Sampling occurred between 3rd October 2022 and 14th June 2024. Participant data was collected via questionnaires completed by household members, capturing demographics, building characteristics, and respiratory health. Passive air samplers were deployed in living rooms for 28 days during two seasonal campaigns, with concurrent outdoor sampling at four fixed community sites. Fungal bioaerosols were identified by ITS2 amplicon sequencing and quantified using broad-range qPCR targeting the 18S rRNA gene. Diversity indices and temporal dynamics were analysed using ecological statistics and generalised additive models.Findings118 households were enrolled, comprising 504 residents (263 female, 237 male, 4 not reported). Of these, 104 households completed both seasonal campaigns and 14 completed one, yielding 262 air samples (222 indoor, 40 outdoor). DNA was successfully recovered from all samples, identifying 2,027 fungal genera. Indoor environments showed significantly higher richness (mean 646 vs 495 ASVs; p<0.0001) and Shannon diversity (4.21 vs 3.53; p<0.0001) than outdoors. Community composition differed markedly (PERMANOVA p<0.0001), with Penicillium, Aspergillus, and Wallemia enriched in
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Journal articleRhodes J, Fisher M, 2026,
Emerging terbinafine-resistant Trichophyton indotineae between 2018 and 2023: a multinational genomic epidemiology study
, The Lancet Microbe, ISSN: 2666-5247 -
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 articleKoo WLY, Thng KX, Tiew PY, et al., 2026,
The Airway Microbiome in Chronic Obstructive Pulmonary Disease (COPD): A Guide for Clinicians.
, Br J Hosp Med (Lond), Vol: 87Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory condition marked by chronic symptoms and frequent exacerbations, contributing to significant morbidity and mortality. The advent of molecular microbiology and next-generation sequencing (NGS) has expanded our understanding of the lung microbiome, and integration of microbiome datasets with other omics reveals important microbial-metabolic-immuno-inflammatory interactions that influence COPD pathogenesis. Recent studies have highlighted dysbiosis of the airway microbiome, with shifts in bacterial, viral, and fungal communities playing a crucial role in disease progression, exacerbations and clinical outcomes. Moreover, microbiome changes are observed in COPD associated overlap syndromes, complicating diagnosis and treatment. This review synthesizes current microbiome research in COPD, focusing on its clinical relevance, including its potential as a diagnostic and prognostic tool. We additionally discuss the challenges of integrating microbiome data into clinical practice, emphasizing the need for personalized, precision medicine approaches to optimize COPD management and improve patient outcomes.
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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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