Recent Publications

Epidemics. 2026 Jul 1;56:100931. doi: 10.1016/j.epidem.2026.100931. Online ahead of print.

ABSTRACT

Accurate parameter estimation is fundamental to quantitative epidemiology as it provides the foundation for robust modelling and evidence-based decision-making. We present a novel two-stage framework, that is designed to enhance computational efficiency for parameter estimation of complex, stochastic, or spatially explicit models. Traditional Approximate Bayesian Computation (ABC) methods often face prohibitive costs when likelihoods are analytically intractable and acceptance rates are low. Our hybrid approach, ABC-RF-rejection, integrates ABC rejection sampling with Random Forest (RF) classification to selectively identify parameter sets likely to satisfy observed data constraints. In the first stage, a small-scale ABC rejection step generates a labelled training dataset of accepted and rejected particles. In the second stage, a trained RF model decouples posterior exploration from expensive forward simulations by predicting acceptance probabilities for a substantially larger candidate set. This allows the algorithm to focus computational resources on high-probability regions of the parameter space. We apply the ABC-RF-rejection approach to three distinct epidemiological contexts: stochastic simulations of onchocerciasis vector control, spatially explicit modelling of cassava brown streak virus spread in Uganda, and the 2014-2015 West Africa Ebola outbreak in heterogeneous populations. This framework provides an adaptable and robust solution for rapid, evidence-based decision-making in settings characterised by spatial heterogeneity, stochasticity, and limited surveillance data.

PMID:42419005 | DOI:10.1016/j.epidem.2026.100931

EMBO Rep. 2026 Jul 7. doi: 10.1038/s44319-026-00861-x. Online ahead of print.

ABSTRACT

Amoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identifies accumulation of endo-lysosomes decorated with the lipid kinases VPS34-PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulates speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2 generated by the sequential action of VPS34 and PIKfyve, mediates Ca2+ efflux from lysosomes via the mucolipin TRP cation channel 1 (TRPML1), thus controlling activity of myosin IIA and hence the generation of propulsive force through retrograde actin flow. The VPS34-PIKfyve kinases also regulate velocity of myeloid cells, as well as of the amoeba Dictyostelium discoideum - establishing the axis as an evolutionarily conserved speed control system of amoeboid cell migration.

PMID:42414599 | DOI:10.1038/s44319-026-00861-x

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-59438-2. Online ahead of print.

ABSTRACT

Cassava brown streak disease (CBSD) is a major threat to smallholder farmers in sub-Saharan Africa (SSA), where cassava is a staple crop. Caused by cassava brown streak ipomoviruses (CBSIs), CBSD has spread extensively since its detection in Uganda in 2004, raising concerns about ongoing spread through Southern and Central Africa and potential expansion to West Africa, home to the world's largest cassava producer, Nigeria. Building on a stochastic epidemiological model that predicts CBSD spread at the scale of Uganda, we incorporate extensive field surveillance records to extend the model to all thirty-two major cassava-producing countries in SSA. We then deploy the model to address key strategic questions such as estimating the present day CBSD distribution and predicting rates of ongoing spread towards West Africa. We also evaluate the risk of direct introductions resulting from extreme cases of long-range movement of infected planting material by air, sea or land, which could trigger outbreaks far beyond normal dispersal limits. Our model predicts the likely arrival of CBSD in Nigeria via cross-continental spread within 25 years, and if directly introduced anywhere in West Africa, spreading to most West African nations within 10 years of introduction. The risks of ongoing and future CBSD spread highlighted in this study underscore the need for proactive phytosanitation measures, including clean seed programs, vector control, and quarantine policies to curb CBSD spread. Moreover, the model described in this study not only provides estimates for arrival times across SSA, but also lays the foundations for a continental-scale quantitative framework wherein both surveillance and management options can be explored and optimised.

PMID:42393109 | DOI:10.1038/s41598-026-59438-2

NPJ Vaccines. 2026 Jul 2. doi: 10.1038/s41541-026-01516-7. Online ahead of print.

ABSTRACT

The ongoing evolution of SARS-CoV-2, particularly the emergence and rapid spread of new immune-evasive variants, continues to challenge the durability of vaccine-induced protection. Understanding how repeated variant exposures shape neutralizing antibody breadth is therefore essential for optimizing booster design. Here, we investigated polyclonal neutralizing antibody responses in individuals who received a bivalent (ancestral + BA.4/5) boost followed by an additional monovalent XBB.1.5 boost, with and without breakthrough infection, against a diverse panel of SARS-CoV-2 variants. To visualize human multi-exposure immunity in antigenic space via antibody landscapes, we extended our existing human sera-based antigenic map with hamster sera infected with more recent variants. The hamster sera allowed us to map BA.2.86 and JN.1 variants, which largely escape human single exposure sera. Our analysis of human multi-exposure sera revealed that the number and type of exposures significantly shaped antibody landscapes. The XBB.1.5 booster immunization notably increased neutralizing antibody titers across variants, elevating the height of the antibody landscape. However, titers against more recent Omicron variants, such as JN.1, were low despite booster administration. These findings highlight the dynamic nature of SARS-CoV-2 immunity and emphasize the need for continuous monitoring and adaptation of vaccine strategies to maintain effective protection against emerging variants.

PMID:42386782 | DOI:10.1038/s41541-026-01516-7

NPJ Vaccines. 2026 Jul 1;11(1):125. doi: 10.1038/s41541-026-01469-x.

ABSTRACT

The combined threats of future sarbecovirus zoonosis and continually emerging SARS-CoV-2 VOCs highlight the need to assess the breadth of existing SARS-CoV-2 vaccine-mediated protection. Here, we investigate a cohort of older individuals who received four COVID-19 vaccine doses, for potential cross-neutralisation against lentiviral particles bearing spikes from either Omicron VOCs or other sarbecoviruses. Despite recent fourth bivalent mRNA vaccine doses (encoding SARS-CoV-2 Wu-1 and Omicron spikes), neutralisation of Omicron lineage VOCs was reduced compared to Wu-1, consistent with an imprinted immune response. Similarly, particles bearing either SARS-CoV-1 or a SARS-CoV-1-related bat sarbecovirus spike were neutralised less efficiently than Wu-1. Unexpectedly, however, we observed that particles with spikes from two animal SARS-CoV-2-related viruses, BANAL-20-52 from bats and a pangolin CoV, were significantly more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-neutralisation and potential protection against certain animal sarbecoviruses.

PMID:42386763 | DOI:10.1038/s41541-026-01469-x

Cell Rep Methods. 2026 Jun 29:101508. doi: 10.1016/j.crmeth.2026.101508. Online ahead of print.

ABSTRACT

Antigenically diverse pathogens such as coronaviruses pose substantial global health threats, highlighting the need for broad-spectrum vaccines. Here, we introduce Spectravax, a computational method that designs broad-spectrum vaccines accounting for genetic diversity in both host and pathogen populations. Using Spectravax, we designed a nucleocapsid (N) antigen to elicit cross-reactive immune responses to viruses from the Sarbecovirus and Merbecovirus subgenera of Betacoronaviruses. In silico analyses demonstrated superior predicted host and pathogen coverage for Spectravax compared to wild-type sequences and existing computational designs. Experimental validation in mice supported these predictions: Spectravax N elicited robust immune responses to SARS-CoV, SARS-CoV-2, and MERS-CoV-the three coronaviruses responsible for major outbreaks in humans since 2002-while wild-type and existing computational designs elicited limited responses. Furthermore, we identified the MERS-CoV N epitopes responsible for Spectravax's cross-reactivity, advancing the rational design of broad-spectrum vaccines for pandemic preparedness.

PMID:42372721 | DOI:10.1016/j.crmeth.2026.101508

Comput Struct Biotechnol J. 2026 Jun 26;35(1):0143. doi: 10.34133/csbj.0143. eCollection 2026.

ABSTRACT

Glycosphingolipids (GSLs) are essential components of biological membranes with important roles in cell signaling. Disrupted GSL metabolism is associated with malignancy across a range of cancers, with different GSLs implicated in distinct tumors. GSLs have potential mechanistic roles in cancer; however, their functions in lower-grade gliomas (LGGs) remain poorly understood. We present ensemble machine learning approaches using transcriptomic data from LGG, combined with GSL-specific metabolic simulations, to predict survival outcomes. The ensemble approach demonstrates effective risk stratification for LGG patients based on GSL synthetic enzyme expression. Pathway analysis of model-derived risk groups identified correlations with GSL-modulated pathways including cell motility, division, and Wnt signaling in LGG pathology. Given the strong performance of machine learning approaches to predict survival outcomes and that GSLs are shed into the tumor microenvironment, GSL-based diagnostics and prognostics may prove to be clinically beneficial upon future experimental validation. A Python package enabling GSL-specific metabolic modeling and risk prediction from RNA sequencing data is provided.

PMID:42368494 | PMC:PMC13305194 | DOI:10.34133/csbj.0143

Nat Commun. 2026 Jun 26. doi: 10.1038/s41467-026-74866-4. Online ahead of print.

ABSTRACT

Vaccines work by inducing an immunological memory response to protect against infection or disease. More effective vaccines are required to improve protection of high-risk groups such as the elderly. Here we screen transcriptional signatures of T cell memory against repurposable drug signatures, identifying a subclass of lysine deacetylase inhibitors (KDACi) capable of promoting a memory precursor phenotype in primary T cells. Leveraging combined acetylomic, metabolomic, transcriptomic and epigenomic analyses, we identify enhanced glutaminolysis as the mechanism responsible for the KDACi effect, with selective inhibition reversing the changes induced by KDACi treatment. We validate the ability of a repurposable KDACi (sodium valproate) to promote immune memory in four murine models of infection and immunisation, with the effect reversed by concurrently inhibiting glutaminolysis. Finally, we undertake a human challenge study, which demonstrates a 10-fold increase in correlates of protection following seasonal influenza vaccination. These results reveal immune-metabolic adjuvant properties of repurposable lysine deacetylase inhibitors and demonstrate that systematic screening can identify both efficacy and mechanism of repurposable drugs.

PMID:42362565 | DOI:10.1038/s41467-026-74866-4

J Vet Intern Med. 2026 May 4;40(3):aalag118. doi: 10.1093/jvimsj/aalag118.

ABSTRACT

BACKGROUND: Non-specialist vets are often required to make decisions in the absence of specialist knowledge and support. Care pathways (CPs) use knowledge engineering to convert expert knowledge into a computer-interpretable format, delivered to clinicians at the point-of-care via patient-specific clinical decision recommendations.

HYPOTHESIS/OBJECTIVES: Non-specialist vets make diagnostic and management decisions that are more consistent with specialists when they have access to CP decision support.

ANIMALS: Clinical information from 8 historical cases of dogs with myelopathy presenting to a university referral hospital with para/tetra-paresis/plegia were used for the study.

METHODS: A CP was developed to prioritize differential diagnoses and provide management recommendations for cases of dogs with myelopathy resulting in para/tetra-paresis/plegia. A crossover study was then performed comparing answers 45 non-specialist vets and 17 final-year vet students gave to case-based questions for 8 clinical cases, with and without the use of the CP. Each participant answered half the questions without any decision support (CP-) and half the questions with CP decision support (CP+), with the question order randomized each time. Participant answers were then scored against a pre-agreed expert consensus, represented by the full score of 100 points.

RESULTS: Mean scores were improved by 40.4 points (95% CI [36.4, 44.4]), P < .05) for differential diagnosis listing and prioritization and 7.1 points (95% CI [2.3, 11.6]), P < .05) for management decisions when using the CP.

CONCLUSIONS AND CLINICAL IMPORTANCE: CP clinical decision support could be a useful adjunctive tool for non-specialist vets, particularly in supporting their ability to produce prioritized differential diagnoses.

PMID:42348907 | DOI:10.1093/jvimsj/aalag118

Acta Crystallogr D Struct Biol. 2026 Jul 1. doi: 10.1107/S2059798326005723. Online ahead of print.

ABSTRACT

The application Scotty, implemented within the Phasertng codebase, was used to perform a PDB-wide analysis of lattice coincidences. Using a broad definition of lattice coincidence, the number of distinct lattice clusters is approximately half the total number of crystallographic PDB entries. In over one thousand lattice clusters entries are reported in different space groups, consistent with pseudo-symmetric variation within a common lattice framework. Space-group frequencies computed at the lattice-coincidence level update those obtained by entry-based counting, and more accurately reflect priors for novel crystal forms. Combining lattice clustering with sequence identity and deposited oligomeric annotations reveals multiple cases of inconsistent biological assembly assignments among structures sharing near-identical lattices, suggesting an opportunity to improve annotations. The survey also identifies a range of protein systems forming extended in cellulo paracrystalline arrays, including storage, sequestration, toxin and membrane-associated proteins, an understudied area of structural biology. Overall, the results demonstrate that lattice-level analysis provides a valuable perspective on macromolecular self-association.

PMID:42339564 | DOI:10.1107/S2059798326005723

Acta Crystallogr D Struct Biol. 2026 Jul 1. doi: 10.1107/S2059798326005711. Online ahead of print.

ABSTRACT

When a macromolecular crystal lattice targeted for study is closely related to a previously studied crystal lattice, phasing the target crystal by difference (fast-)Fourier transform (DFFT) methods is preferable to performing molecular replacement. The application Scotty, within the Phasertng codebase, is software for the identification of coincident lattices and downstream processing. All crystallographic PDB entries are organized into a scikit-learn `BallTree' index under the Niggli cell distance metric `NCDist'. Nearest neighbours under the metric are progressed to test structure-factor intensity correlation. The structure from the lattice with the highest correlation with the target is used to phase the target lattice, and the coordinates are taken forward to coordinate refinement using a wide convergence radius protocol. The method can identify lattice coincidences accounting for very significant non-isomorphism. The nearest-neighbour search is space-group agnostic, so that coincident lattices are identified even when the nominal space groups are different, the symmetry of one lattice being described as a subgroup of the other or a higher metric symmetry.

PMID:42339563 | DOI:10.1107/S2059798326005711

Virus Evol. 2026 Jun 1;12(1):veag032. doi: 10.1093/ve/veag032. eCollection 2026.

ABSTRACT

Lassa fever is a viral haemorrhagic fever that poses a persistent public health threat in several West African countries, particularly Nigeria. The scarcity of Lassa virus (LASV) sequences isolated from small mammal reservoirs limits our knowledge and understanding of LASV genomic diversity and transmission dynamics. To address this knowledge gap, we sampled 1189 small mammals, including mice, rats, and shrews, from two LASV-endemic states in southern Nigeria (Ondo and Ebonyi States) and tested them for the presence of LASV RNA using reverse transcription-quantitative polymerase chain reaction. Selected quantitative polymerase chain reaction-positive samples were subjected to whole genome sequencing and small mammal speciation through next-generation sequencing outputs. We recorded an overall polymerase chain reaction positivity rate of 61.6%, with rat species demonstrating the highest LASV prevalence. We also conducted a serosurvey of 269 small rodents using indirect Enzyme-Linked Immunosorbent Assay (ELISA) and obtained an overall anti-LASV seroprevalence of 45%. Using the Nextera XT metagenomic sequencing protocol, we produced 55 LASV partial (n = 28) and full-length genomes (n = 27) from small mammals sampled, all of which clustered within sublineage 2g. LASV sequences generated from this study suggest that LASV variation is mostly driven by location, as isolates from this study tend to cluster more closely with other isolates collected from within the same region, rather than by collection date or host. However, samples collected from Ebonyi State were more closely related to isolates collected in Ondo State than to isolates from Edo, despite a larger physical distance. Overall, the data from this study suggest free movement of the virus across states in Nigeria, among humans and various non-human taxa. The finding of LASV in additional small mammal hosts suggests that the virus reservoir is vast and may include many small mammals not well-characterized.

PMID:42339070 | PMC:PMC13285998 | DOI:10.1093/ve/veag032

Mol Cell. 2026 Jun 19:S1097-2765(26)00385-0. doi: 10.1016/j.molcel.2026.06.014. Online ahead of print.

ABSTRACT

Adaptation to fluctuating nutrient supply is essential for organismal survival, but how human cells monitor the abundance of many critical nutrients remains undefined. Characterizing the conditional degradation of CDO1, the critical enzyme responsible for cysteine catabolism, here we identify a Cullin-RING E3 ligase complex defined by the substrate adaptor LRRC58 that is sensitive to cysteine abundance. When cysteine is replete, LRRC58 activity is restrained through ubiquitination and proteasomal degradation. Upon cysteine deprivation, LRRC58 is stabilized to permit CDO1 degradation. Through saturation mutagenesis stability profiling, we systematically validate a structural model of the CDO1-LRRC58 interaction and identify residues at the LRRC58 C terminus required for cysteine-dependent instability. CDO1 degradation prevents ferroptotic cell death upon cysteine scarcity, and CDO1 mutations causing neurodevelopmental defects in humans encode dominant-active proteins refractory to LRRC58 recognition. Altogether, these data reveal the CDO1-LRRC58 axis as a critical regulator of cysteine homeostasis that safeguards neural development.

PMID:42320481 | DOI:10.1016/j.molcel.2026.06.014

Chemistry. 2026 Jun 18:e71280. doi: 10.1002/chem.71280. Online ahead of print.

ABSTRACT

Multi-receptor peptide agonists represent an effective strategy for obesity treatment, extending the success of incretin-based therapies through simultaneous engagement of complementary targets. Their development, however, is synthetically demanding, as each receptor combination typically requires de novo preparation of large fusion peptides. We report a modular polyethylene glycol (PEG)-based scaffold that enables orthogonal attachment of up to three functional components, including therapeutic peptides, half-life-extending units, and other labels, via sequential strain-promoted azide-alkyne cycloaddition (SPAAC) and copper-catalysed azide-alkyne cycloaddition (CuAAC). The scaffold is assembled on solid phase without intermediate purification, providing a readily accessible and versatile linker. Using glucagon-like peptide-1 (GLP-1) and amylin receptor agonists as a proof-of-concept, dual-agonist constructs with tuneable valency and functionality were rapidly generated. Lead conjugates displayed balanced, low-picomolar potency at both receptors in cyclic adenosine monophosphate (cAMP) assays and showed selective receptor-mediated internalisation in GLP-1 receptor-expressing cells. This orthogonal click-based platform enables rapid and modular multi-agonist assembly, facilitating systematic exploration of receptor combinations, valency, and payload effects. Beyond incretin biology, it offers a general route to multifunctional peptide therapeutics and diagnostics.

PMID:42315994 | DOI:10.1002/chem.71280

Emerg Med J. 2026 Jun 18:emermed-2026-215891. doi: 10.1136/emermed-2026-215891. Online ahead of print.

NO ABSTRACT

PMID:42315322 | DOI:10.1136/emermed-2026-215891

Arch Virol. 2026 Jun 18;171(7):215. doi: 10.1007/s00705-026-06672-8.

ABSTRACT

The COVID-19 pandemic highlighted the potential of oral antiseptic agents to reduce viral transmission. Strategies that enhance and sustain antiviral activity in the oral cavity may further support control of respiratory viruses. In this study, we evaluated the virucidal activity of selected antiseptic agents against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), individually and in combination, under controlled in vitro conditions. Cetylpyridinium chloride (CPC), benzethonium chloride (BZT), thymol, and tannic acid were assessed using a quantitative suspension assay in the presence of mucin and representative mucoadhesive polymers. Dynamic light scattering and zeta potential analyses were performed to characterize interactions between active agents and mucin or polymers. CPC, BZT, and thymol exhibited dose-dependent viral inactivation. CPC reduced IAV and SARS-CoV-2 titres by approximately 4 log₁₀ at > 200 µg/mL and 25 µg/mL, respectively, while thymol achieved comparable reductions at 1000 µg/mL and 750 µg/mL. Tannic acid showed minimal virucidal activity. Notably, CPC-thymol and BZT-thymol combinations achieved > 4 log₁₀ reductions at substantially lower concentrations than individual agents, indicating enhanced virucidal activity and improved cytocompatibility. Mucin markedly attenuated the virucidal activity of CPC-thymol combinations; however, selected polymers partially preserved antiviral efficacy under mucin-rich conditions. Physicochemical analyses suggest that electrostatic, hydrophobic, and hydrogen-bonding interactions contribute to these effects. These findings demonstrate the enhanced antiviral activity of quaternary ammonium compound-thymol combinations and highlight the influence of mucosal components and macromolecules interactions in modulating oral antiseptic activity.

PMID:42310234 | DOI:10.1007/s00705-026-06672-8

Sci Transl Med. 2026 Jun 17;18(854):eadx4108. doi: 10.1126/scitranslmed.adx4108. Epub 2026 Jun 17.

ABSTRACT

The expanding global crisis of bacterial infections caused by antimicrobial-resistant pathogens has resulted in an urgent need for therapeutics. Previous efforts to target pathogen surface antigens with monoclonal antibodies (mAbs) have sought to activate the complement system, primarily through the antibody-dependent classical pathway. However, most mAbs have induced insufficient complement activation because pathogen evasion strategies disrupt the complex spatiotemporal requirements for activation of the classical pathway initiation complex C1. To address this, we developed a targeted complement activation therapy (T-CAT), which uses antibodies furnished with the enzymatic capability to initiate complement activation directly on the bacterial surface without involvement of the classical pathway initiation complex. We found that T-CAT mAbs directed against bacterial surface antigens can overcome the strategies that pathogens evolved to escape from classical pathway-mediated clearance by the immune system. We further demonstrated that T-CAT mAbs could safely and effectively be used to treat infectious disease in experimental murine models of sepsis and pneumonia caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Neisseria meningitidis. Together, these data highlight the potential for T-CAT as a next-generation mAb platform with broad applicability against diverse microbial species, including multidrug-resistant pathogens, without promoting drug resistance.

PMID:42308332 | DOI:10.1126/scitranslmed.adx4108

Cell Chem Biol. 2026 Jun 15:S2451-9456(26)00187-X. doi: 10.1016/j.chembiol.2026.05.008. Online ahead of print.

ABSTRACT

Regulated cell death (RCD) plays a central role in host defenses against infection. It is also an important driver of pathology in sepsis. The proteins that regulate RCD in mice and, to a lesser degree, in humans are increasingly well understood. In other species, how RCD, especially pyroptosis, occurs in response to infection is less clear. In this review, we outline what is currently known about genes involved in RCD with a focus on pyroptosis across different species and consider the potential consequences that the genetic diversity might have on the host response to infection.

PMID:42296960 | DOI:10.1016/j.chembiol.2026.05.008

Front Cell Infect Microbiol. 2026 May 29;16:1813484. doi: 10.3389/fcimb.2026.1813484. eCollection 2026.

ABSTRACT

The interferon system, first discovered in chicken embryonated eggs, plays a pivotal role in defending vertebrates against pathogens, yet comprehensive multi-omics analyses of immune responses in avian species remain scarce. In this study, we employed an integrative approach combining RNA-Seq transcriptomics with SILAC-based quantitative proteomics to characterize global changes in gene and protein expression following immune stimulation in DF-1 chicken fibroblasts. Cells were treated with three distinct immune stimuli: chicken type I interferon, the synthetic double-stranded RNA (dsRNA) analog poly(I:C), and Infectious Bursal Disease Virus (IBDV), a birnavirus with a bi-segmented dsRNA genome. Our analysis revealed a core set of over 110 genes consistently upregulated across all conditions, representing conserved components of the antiviral response. Each stimulus also triggered distinct transcriptional programs, with poly(I:C) eliciting the most robust cytokine induction. At the proteomic level, we quantified more than 2,400 proteins, uncovering asymmetric regulatory patterns in which upregulated proteins exhibited greater fold changes than those that were downregulated. Notably, analysis of transcription-translation coupling revealed a moderate overall correlation between mRNA and protein abundance, which was significantly attenuated following poly(I:C) stimulation, likely reflecting PKR-mediated translational arrest. Ontological analysis corroborated the upregulation of interferon-stimulated genes and proteins involved in inhibiting viral genome replication, as expected. Intriguingly, proteins associated with mitochondrial metabolism and protein synthesis were consistently downregulated, suggesting a coordinated suppression of cellular bioenergetic and translational functions during the antiviral response. These findings underscore the critical role of post-transcriptional regulation in shaping the innate immune landscape, as numerous proteins exhibited altered expression without corresponding mRNA changes. Collectively, this study provides a comprehensive resource for dissecting cellular avian immune signaling and demonstrates the power of integrative multi-omics approaches in uncovering the complex regulatory networks governing host defense.

PMID:42291312 | PMC:PMC13259848 | DOI:10.3389/fcimb.2026.1813484

BMC Med Res Methodol. 2026 Jun 13. doi: 10.1186/s12874-026-02907-z. Online ahead of print.

ABSTRACT

BACKGROUND: The United Kingdom has a history of world-leading health research, showcased most recently in its response to the Covid pandemic. However, while the UK's performance in academic clinical research remains strong, its global position in the delivery of commercial research has declined. In 2023 Lord O'Shaughnessy reviewed the barriers and drivers to the delivery of commercial trials, identifying 27 recommendations to improve commercial trial performance. Highlighted within the report was the importance of the UK being globally competitive in the delivery of its trials, including study set up and approval times.

METHODS: A dataset from the National Institute for Health and Care Research (NIHR), containing 28,188 site observations from 5,421 unique commercial studies provided data on first recruits to commercial studies spanning a 15-year period from 2010 to 2024. Where there were issues with data quality or reliability, data were cleaned, leaving 23,622 observations from 4,849 studies for analysis. Logistic regression and generalised linear mixed effects models were applied to determine whether sites that recruited their first participant to commercial studies more quickly had a higher probability of recruiting to time and target.

RESULTS: Sites that recruited their first participant more quickly were significantly more likely to recruit to time and target (RTT); (odds ratio per one-month increase in time 0.88, 95% CI 0.87 to 0.89, p < 0.0001). The model suggests that the predicted probability of RTT for a site falls to < 50% if it takes more than 8 months to recruit its first participant. A secondary analysis showed a highly significant increase in probability of a site meeting RTT if they recruited the 'first' Global, European or UK participants onto a study (odds ratio 2.96, 95% CI 2.20 to 4.05, p < 0.0001).

CONCLUSIONS: Sites that recruit first participants more quickly are more likely to recruit to time and target in commercial studies. This is likely to lead to them being selected by sponsors to participate in subsequent studies, increasing research opportunities for their patients and revenue for their organisation. Achieving quicker firsts requires proactive planning and coordination by R&D departments and study teams. Setting up sites in a timely manner is a key determinant of successful study delivery and a key component of the UK government's 10-Year Health Plan for England and Life Sciences Sector Plan.

TRIAL REGISTRATION: Not applicable.

PMID:42288738 | DOI:10.1186/s12874-026-02907-z