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• Journal article
  Balmes A, Rodriguez JG, Seifert J, Pinto-Quintero D, Khawaja AA, Boffito M, Frye M, Friebe A, Emerson M, Seta F, Feil R, Feil S, Schaffer TEet al., 2024,

  Role of the NO-GC/cGMP signaling pathway in platelet biomechanics

  , PLATELETS, Vol: 35, ISSN: 0953-7104
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• Journal article
  Asimakidou E, Reynolds R, Barron AM, Lo CHet al., 2024,

  Autolysosomal acidification impairment as a mediator for TNFR1 induced neuronal necroptosis in Alzheimer's disease

  , NEURAL REGENERATION RESEARCH, Vol: 19, ISSN: 1673-5374
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• Journal article
  Woodruff JL, Bykalo MK, Loyo-Rosado FZ, Maissy ES, Sadek AT, Hersey M, Erichsen JM, Maxwell ND, Wilson MA, Wood SK, Hashemi P, Grillo CA, Reagan LPet al., 2024,

  Differential effects of high-fat diet on endocrine, metabolic and depressive-like behaviors in male and female rats

  , APPETITE, Vol: 199, ISSN: 0195-6663
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• Journal article
  Marchal A, Cirulli ET, Neveux I, Bellos E, Thwaites RS, Schiabor Barrett KM, Zhang Y, Nemes-Bokun I, Kalinova M, Catchpole A, Tangye SG, Spaan AN, Lack JB, Ghosn J, Burdet C, Gorochov G, Tubach F, Hausfater P, COVID Human Genetic Effort, COVIDeF Study Group, French COVID Cohort Study Group, CoV-Contact Cohort, COVID-STORM Clinicians, COVID Clinicians, Orchestra Working Group, Amsterdam UMC COVID-19 Biobank, NIAID-USUHS COVID Study Group, Dalgard CL, Zhang S-Y, Zhang Q, Chiu C, Fellay J, Grzymski JJ, Sancho-Shimizu V, Abel L, Casanova J-L, Cobat A, Bolze Aet al., 2024,

  Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

  , HGG Advances, Vol: 5, ISSN: 2666-2477

  Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

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• Journal article
  Koysombat K, Mukherjee A, Nyunt S, Pedder H, Vinogradova Y, Burgin J, Dave H, Comninos AN, Talaulikar V, Bailey JV, Dhillo WS, Abbara Aet al., 2024,

  Factors affecting shared decision-making concerning menopausal hormone therapy.

  , Ann N Y Acad Sci

  Menopausal hormone therapy (MHT) is an effective treatment for menopause-related symptoms. Menopause management guidelines recommend a personalized approach to menopause care, including MHT use. Decision-making around menopause care is a complex, iterative process influenced by multiple factors framed by perspectives from both women and healthcare providers (HCPs). This narrative review aims to summarize evidence around factors affecting decision-making regarding menopause-related care. For HCPs, the provision of individualized risk estimates is challenging in practice given the number of potential benefits and risks to consider, and the complexity of the data available, especially within time-limited consultations. Women seeking menopause care have the difficult task of making sense of the benefit versus risk profiles to make choices in line with their decisional needs influenced by sociocultural/economic, educational, demographic, and personal characteristics. The press, social media, and influential celebrities also impact the perception of menopause and decision-making around it. Understanding these factors can lead to improved participation in shared decision-making, satisfaction with the decision and decision-making process, adherence to treatment, reduced decisional regret, efficient use of resources, and ultimately long-term satisfaction with care.

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• Journal article
  Dabas R, Kamaly N, 2024,

  Redox-Responsive Nanogels for Precision Protein Delivery

  , European Polymer Journal, Vol: 215, ISSN: 0014-3057

  Redox-responsive drug carriers present a therapeutically viable delivery platform owing to their ability to leverage the intracellular redox environment. In this work, we describe a facile, one-pot aqueous-based synthetic methodology for encapsulating sensitive biological payloads within redox-responsive crosslinked nanogels. We systematically evaluate the impact of various disulphide-based crosslinkers on the morphology, stability, encapsulation and loading capacities of these nanogels. In vitro assessments were conducted to elucidate the ease of delivery of functional protein payloads, using fluorescently-labelled bovine serum albumin and the enzyme, paraoxonase-1. The nanogels demonstrate promising delivery efficiencies with minimal cytotoxicity in vitro. The simplicity of their synthesis, along with the precise control achieved in nanogel degradation and payload release kinetics, not only enriches our understanding of redox-responsive nanosystems but also underscores their potential to catalyze transformative advancements in intracellular protein delivery.

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• Journal article
  Pennisi I, Cavuto ML, Miglietta L, Malpartida-Cardenas K, Stringer OW, Mantikas K-T, Reid R, Frise R, Moser N, Randell P, Davies F, Bolt F, Barclay W, Holmes A, Georgiou P, Rodriguez-Manzano Jet al., 2024,

  Rapid, portable, and electricity-free sample extraction method for enhanced molecular diagnostics in resource-limited settings

  , Analytical Chemistry, Vol: 96, Pages: 11181-11188, ISSN: 0003-2700

  The COVID-19 pandemic has highlighted the need for rapid and reliable diagnostics that are accessible in resource-limited settings. To address this pressing issue, we have developed a rapid, portable, and electricity-free method for extracting nucleic acids from respiratory swabs (i.e. nasal, nasopharyngeal and buccal swabs), successfully demonstrating its effectiveness for the detection of SARS-CoV-2 in residual clinical specimens. Unlike traditional approaches, our solution eliminates the need for micropipettes or electrical equipment, making it user-friendly and requiring little to no training. Our method builds upon the principles of magnetic bead extraction and revolves around a low-cost plastic magnetic lid, called SmartLid, in combination with a simple disposable kit containing all required reagents conveniently prealiquoted. Here, we clinically validated the SmartLid sample preparation method in comparison to the gold standard QIAamp Viral RNA Mini Kit from QIAGEN, using 406 clinical isolates, including 161 SARS-CoV-2 positives, using the SARS-CoV-2 RT-qPCR assays developed by the US Centers for Disease Control and Prevention (CDC). The SmartLid method showed an overall sensitivity of 95.03% (95% CI: 90.44-97.83%) and a specificity of 99.59% (95% CI: 97.76-99.99%), with a positive agreement of 97.79% (95% CI: 95.84-98.98%) when compared to QIAGEN's column-based extraction method. There are clear benefits to using the SmartLid sample preparation kit: it enables swift extraction of viral nucleic acids, taking less than 5 min, without sacrificing significant accuracy when compared to more expensive and time-consuming alternatives currently available on the market. Moreover, its simplicity makes it particularly well-suited for the point-of-care where rapid results and portability are crucial. By providing an efficient and accessible means of nucleic acid extraction, our approach aims to introduce a step-change in diagnostic capabilities for resource-limited sett

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• Journal article
  Thenappan A, Maher TM, Yazbeck L, Jenkins RG, Johnson SR, Stewart I, Oldham JM, Molyneaux PLet al., 2024,

  Competing Causes of Death in Idiopathic Pulmonary Fibrosis.

  , Am J Respir Crit Care Med
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• Journal article
  Turner P, Baseggio Conrado A, Kallis C, O'Rouke E, Haider S, Ullah A, Custovic D, Custovic A, Quint Jet al., 2024,

  Time trends in the epidemiology of food allergy in England: an analysis of national data

  , The Lancet Public Health, ISSN: 2468-2667
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• Journal article
  Chiu C-Y, Willis-Owen S, Wong K, Farrow S, Cookson W, Moffatt M, Zhang Yet al., 2024,

  MAP3K8 is a potential therapeutic target in airway epithelial inflammation

  , Journal of Inflammation, ISSN: 1476-9255

  Background: We have previously discovered clusters of sequentially negative and positive modulators of acute inflammation during cytokine stimulation in epithelial cells and identified potential targets for therapy within these clusters. MAP3K8 is a druggable kinase that we found to be a hub of a principal interaction network. We describe here the results of MAP3K8 knockdown in the A549 lung cancer cell line, the BEAS-2B epithelial cell line and normal human bronchial cells (NHBE) following IL-1β stimulation. We analysed signalling transduction and global gene expression after IL-1β stimulation with and without MAP3K8 knockdown, quantifying levels of the inflammatory cytokines IL-6 and IL-8 levels by qPCRs and ELISAs. We also examined potential small molecule inhibitors for MAP3K8 in the same models. Results: IL-1β significantly and consistently increased MAP3K8 expression after 2 hours in A549, BEAS-2B and NHBE cells. Phosphorylation of MAP3K8 occurred at 20 minutes after IL-1β stimulation and MAP3K8 protein was degraded at 30 minutes. MAP3K8 knockdown significantly reduced IL-6, IL-8 levels after IL-1β stimulation and yielded a 10-fold enhancement of the anti-inflammatory effects of dexamethasone. Phosphorylation of ERK1/2 (P-ERK1/2) and phosphorylation of SAPK/JNK (P-SAPK/JNK) decreased at 30 minutes after IL-1β stimulation with MAP3K8 knockdown. The combination of dexamethasone and MAP3K8 knockdown resulted in greater inhibition of phosphorylated ERK1/2 and SAPK/JNK. Nineteen genes including MMP1, MMP3, MMP10, ITGB8, LAMC2 and PLAT (P corrected <0.01 respectively) demonstrated a distinct altered temporal response to IL-1β following suppression of MAP3K8. However, putative MAP3K8 inhibitors including Tpl2-1, Tpl2-2 and GSK2222867A only showed inhibition of IL-6 and IL-8 production at a high dose.Conclusions: These results confirm that MAP3K8 is a key mediator of the early inflammatory response and that it is a pote

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