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Journal articleDobra R, Pinnell S, Jones A, et al., 2024,
How representative are clinical trial cohorts of the general CF population? Implications for trial planning
, JOURNAL OF CYSTIC FIBROSIS, Vol: 23, Pages: 68-72, ISSN: 1569-1993 -
Journal articleDe Wachter E, Davies JC, Simmonds NJ, et al., 2024,
Letter to the editor: Risk of false newborn screening after intra-uterine exposure to ETI
, JOURNAL OF CYSTIC FIBROSIS, Vol: 23, Pages: 176-177, ISSN: 1569-1993 -
Journal articleSouthern KW, Addy C, Bell SC, et al., 2024,
Standards for the care of people with cystic fibrosis; establishing and maintaining health
, JOURNAL OF CYSTIC FIBROSIS, Vol: 23, Pages: 12-28, ISSN: 1569-1993 -
Journal articleSeymour L, Thrasher A, Baker A, et al., 2024,
The British Society for Gene and Cell Therapy at 20 (2003-2023).
, Hum Gene Ther, Vol: 35, Pages: 5-8The year 2023 marks the 20th anniversary of the British Society for Gene and Cell Therapy (BSGCT). In these 20 years, the field of gene and cell therapy has gone from promising strategy to clinical reality. This report describes the history, objectives, organization, and activities of BSGCT to advance research and practice of gene and cell therapy in the United Kingdom.
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Journal articleDobra R, Davies J, Elborn S, et al., 2024,
A discrete choice experiment to quantify the influence of trial features on the decision to participate in cystic fibrosis trials
, JOURNAL OF CYSTIC FIBROSIS, Vol: 23, Pages: 73-79, ISSN: 1569-1993 -
Journal articleMichael BD, Dunai C, Needham EJ, et al., 2023,
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
, Nature Communications, Vol: 14, ISSN: 2041-1723To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.
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Journal articleThwaites R, Uruchurtu ASS, Negri VA, et al., 2023,
Early mucosal events drive distinct mucosal and systemic antibody responses to live attenuated influenza vaccine
, Nature Communications, Vol: 14, ISSN: 2041-1723Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.
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Conference paperAlton EWFW, Boyd AC, Davies JC, et al., 2023,
LENTIVIRAL VECTOR BASED GENE THERAPY FOR RESPIRATORY DISEASES
, Publisher: MARY ANN LIEBERT, INC, Pages: A28-A28, ISSN: 1941-2711 -
Journal articleMoradi Marjaneh M, Challenger J, salas A, et al., 2023,
Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract
, Journal of Infection, Vol: 87, Pages: 538-550, ISSN: 0163-4453Objectives:The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load.Methods:COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time.ResultsEighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher vir
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Journal articleZivanovic N, Öner D, Abraham Y, et al., 2023,
Single-cell immune profiling reveals markers of emergency myelopoiesis that distinguish severe from mild respiratory syncytial virus disease in infants
, Clinical and Translational Medicine, Vol: 13, ISSN: 2001-1326Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV-infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor-like neutrophils, proliferative monocytes (HLA-DRLow , Ki67+), impaired antigen-presenting function, downregulation of T cell response and low abundance of HLA-DRLow B cells in severe RSV disease. HLA-DRLow monocytes were found as a hallmark of RSV-infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification.
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