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  • Journal article
    Thillai M, Oldham JM, Ruggiero A, Kanavati F, McLellan T, Saini G, Johnson SR, Ble F-X, Azim A, Ostridge K, Platt A, Belvisi M, Maher TM, Molyneaux PLet al., 2024,

    Deep Learning-based Segmentation of CT Scans Predicts Disease Progression and Mortality in IPF.

    , Am J Respir Crit Care Med

    RATIONALE: Despite evidence demonstrating a prognostic role for CT scans in IPF, image-based biomarkers are not routinely used in clinical practice or trials. OBJECTIVES: Develop automated imaging biomarkers using deep learning based segmentation of CT scans. METHODS: We developed segmentation processes for four anatomical biomarkers which were applied to a unique cohort of treatment-naive IPF patients enrolled in the PROFILE study and tested against a further UK cohort. The relationship between CT biomarkers, lung function, disease progression and mortality were assessed. MEASUREMENTS AND MAIN RESULTS: Data was analysed from 446 PROFILE patients. Median follow-up was 39.1 months (IQR 18.1-66.4) with cumulative incidence of death of 277 over 5 years (62.1%). Segmentation was successful on 97.8% of all scans, across multiple imaging vendors at slice thicknesses 0.5-5mm. Of 4 segmentations, lung volume showed strongest correlation with FVC (r=0.82, p<0.001). Lung, vascular and fibrosis volumes were consistently associated across cohorts with differential five-year survival, which persisted after adjustment for baseline GAP score. Lower lung volume (HR 0.98, CI 0.96-0.99, p=0.001), increased vascular volume (HR 1.30, CI 1.12-1.51, p=0.001) and increased fibrosis volume (HR 1.17, CI 1.12-1.22, p=<0.001) were associated with reduced two-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR 3.41; 95% CI 1.36-8.54; p=0.009) and increasing fibrosis volume (HR 2.23; 95% CI 1.22-4.08; p=0.009) were associated with differential survival. CONCLUSIONS: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

  • Journal article
    Devoy E, Hughes D, Alharbi AF, Francis J, Davies JCet al., 2024,

    What is cystic fibrosis screen positive inconclusive diagnosis? And what is it not?

    , ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION, ISSN: 1743-0585
  • Journal article
    Grover M, Gang SS, Troemel ER, Barkoulas Met al., 2024,

    Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans

    , PLoS Biology, Vol: 22, Pages: 1-21, ISSN: 1544-9173

    Protein quality control pathways play important roles in resistance against pathogen infection. For example, the conserved transcription factor SKN-1/NRF up-regulates proteostasis capacity after blockade of the proteasome and also promotes resistance against bacterial infection in the nematode Caenorhabditis elegans. SKN-1/NRF has 3 isoforms, and the SKN-1A/NRF1 isoform, in particular, regulates proteasomal gene expression upon proteasome dysfunction as part of a conserved bounce-back response. We report here that, in contrast to the previously reported role of SKN-1 in promoting resistance against bacterial infection, loss-of-function mutants in skn-1a and its activating enzymes ddi-1 and png-1 show constitutive expression of immune response programs against natural eukaryotic pathogens of C. elegans. These programs are the oomycete recognition response (ORR), which promotes resistance against oomycetes that infect through the epidermis, and the intracellular pathogen response (IPR), which promotes resistance against intestine-infecting microsporidia. Consequently, skn-1a mutants show increased resistance to both oomycete and microsporidia infections. We also report that almost all ORR/IPR genes induced in common between these programs are regulated by the proteasome and interestingly, specific ORR/IPR genes can be induced in distinct tissues depending on the exact trigger. Furthermore, we show that increasing proteasome function significantly reduces oomycete-mediated induction of multiple ORR markers. Altogether, our findings demonstrate that proteasome regulation keeps innate immune responses in check in a tissue-specific manner against natural eukaryotic pathogens of the C. elegans epidermis and intestine.

  • Journal article
    King FJ, Yuen ELH, Bozkurt TO, 2024,

    Border control: manipulation of the host-pathogen interface by perihaustorial oomycete effectors

    , Molecular Plant-Microbe Interactions, Vol: 37, Pages: 220-226, ISSN: 0894-0282

    Filamentous plant pathogens, including fungi and oomycetes, cause some of the most devastating plant diseases. These organisms serve as ideal models for understanding the intricate molecular interplay between plants and the invading pathogens. Filamentous pathogens secrete effector proteins via haustoria, specialized structures for infection and nutrient uptake, to suppress the plant immune response and to reprogram plant metabolism. Recent advances in cell biology have provided crucial insights into the biogenesis of the extrahaustorial membrane and the redirection of host endomembrane trafficking toward this interface. Functional studies have shown that an increasing number of oomycete effectors accumulate at the perihaustorial interface to subvert plant focal immune responses, with a particular convergence on targets involved in host endomembrane trafficking. In this review, we summarize the diverse mechanisms of perihaustorial effectors from oomycetes and pinpoint pressing questions regarding their role in manipulating host defense and metabolism at the haustorial interface. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

  • Journal article
    Mak J, Feary J, Amaral AFS, Marczylo E, Cullinan P, Green DCet al., 2024,

    Occupational exposure to particulate matter and staff sickness absence on the London underground

    , Environment International, Vol: 185, ISSN: 0160-4120

    The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m3), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM2.5. They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM2.5. Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose-response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10-1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM2.5 exposure and may have wider implications for subway workers, contributing to safer working environments.

  • Journal article
    Kowal J, Pino-Bodas R, Arrigoni E, Delhaye G, Suz LM, Duckett JG, Bidartondo MI, Pressel Set al., 2024,

    Assessing above and belowground recovery from ammonium sulfate addition and wildfire in a lowland heath: mycorrhizal fungi as potential indicators

    , RESTORATION ECOLOGY, Vol: 32, ISSN: 1061-2971
  • Journal article
    King FJ, Yuen ELH, Bozkurt O, 2024,

    Border control: manipulation of the host–pathogeninterface by perihaustorial oomycete effectors

    , Molecular Plant-Microbe Interactions, Vol: 37, Pages: 220-226, ISSN: 0894-0282

    Filamentous plant pathogens, including fungi and oomycetes, cause some of the most devastating plant diseases. These organisms serve as ideal models for understanding the intricate molecular interplay between plants and the invading pathogens. Filamentous pathogens secrete effector proteins via haustoria, specialized structures for infection and nutrient uptake, to suppress the plant immune response and to reprogram plant metabolism. Recent advances in cell biology have provided crucial insights into the biogenesis of the extrahaustorial membrane and the redirection of host endomembrane trafficking toward this interface. Functional studies have shown that an increasing number of oomycete effectors accumulate at the perihaustorial interface to subvert plant focal immune responses, with a particular convergence on targets involved in host endomembrane trafficking. In this review, we summarize the diverse mechanisms of perihaustorial effectors from oomycetes and pinpoint pressing questions regarding their role in manipulating host defense and metabolism at the haustorial interface.

  • Journal article
    Sole A, Davies JC, Quintana-Gallego E, 2024,

    Cystic Fibrosis: From Salty Malediction to Possible Cure

    , ARCHIVOS DE BRONCONEUMOLOGIA, Vol: 60, Pages: 129-130, ISSN: 0300-2896
  • Journal article
    Peng H, Darlington APS, South EJ, Chen H-H, Jiang W, Ledesma-Amaro Ret al., 2024,

    A molecular toolkit of cross-feeding strains for engineering synthetic yeast communities

    , Nature Reviews Microbiology, Vol: 9, Pages: 848-863, ISSN: 1740-1526

    Engineered microbial consortia often have enhanced system performance and robustness compared with single-strain biomanufacturing production platforms. However, few tools are available for generating co-cultures of the model and key industrial host Saccharomyces cerevisiae. Here we engineer auxotrophic and overexpression yeast strains that can be used to create co-cultures through exchange of essential metabolites. Using these strains as modules, we engineered two- and three-member consortia using different cross-feeding architectures. Through a combination of ensemble modelling and experimentation, we explored how cellular (for example, metabolite production strength) and environmental (for example, initial population ratio, population density and extracellular supplementation) factors govern population dynamics in these systems. We tested the use of the toolkit in a division of labour biomanufacturing case study and show that it enables enhanced and tuneable antioxidant resveratrol production. We expect this toolkit to become a useful resource for a variety of applications in synthetic ecology and biomanufacturing.

  • Journal article
    Brandfellner L, Muratspahic E, Bismarck A, Mueller HWet al., 2024,

    Quantitative description of polymer drag reduction: Effect of polyacrylamide molecular weight distributions

    , JOURNAL OF NON-NEWTONIAN FLUID MECHANICS, Vol: 325, ISSN: 0377-0257

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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