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Journal articleGuerrero-Fonseca IM, Hernández-Almaraz KB, León-Vega II, et al., 2026, , J Cell Biol, Vol: 225
The adhesive interactions of neutrophils with postcapillary venules during inflammation have been well studied. However, how neutrophils trigger molecular changes in endothelial cells (EC) during their extravasation requires further exploration. The endothelial actin-binding protein cortactin regulates endothelial contacts and neutrophil-endothelial interactions, but the associated mechanisms remain elusive. Hypothesizing that endothelial cortactin dynamics change during inflammation, using super-resolution confocal microscopy of inflamed mouse cremasteric venules and HUVEC, we report that neutrophil interaction with EC induces reduction in EC cortactin levels. This response was specifically mediated by neutrophil serine proteases, including cathepsin G, that were detected inside EC. The observed cortactin degradation was abolished after inhibition of serine proteases or blockade of neutrophil exocytosis. Finally, the endogenous serine protease inhibitor α1-antitrypsin suppressed cortactin degradation in vivo and reduced neutrophil adhesion and extravasation. Collectively, our data unveil a new mechanism by which neutrophils manipulate proteins inside EC to facilitate their extravasation.
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Journal articleYang W, Giblin SP, Pease JE, 2026, , Basic Clin Pharmacol Toxicol, Vol: 139
CXCL17 was recently reported to activate GPR25, a receptor expressed by T-regulatory cells. Although classified as a chemokine, the activity of CXCL17 is ablated by minor C-terminal truncation, suggesting a novel mode of receptor activation. We set out to test this hypothesis by mutagenesis. GPR25 was expressed in the murine pre-B cell line L1.2 and mediated robust migration of transfectants to nanomolar concentrations of recombinant CXCL17 (24-119). The N-terminally truncated form of CXCL17 (64-119) was also chemotactic for GPR25 transfectants, albeit with severely reduced potency. Modelling of CXCL17:GPR25 implied multiple interactions between the N- and C-termini of CXCL17 with GPR25, which was validated by mutagenesis. Cells expressing a chimeric FPR1:GPR25 construct responded chemotactically to CXCL17 but with significantly reduced potency compared with wild-type GPR25 transfectants, implicating the GPR25 N-terminus in CXCL17 recognition. Mutagensis of the GPR25 residues W95, R178 and R264 resulted in a complete loss of chemotactic responsiveness to CXCL17, consistent with the residues interacting with the C-terminal CXCL17 motif. In conclusion, we verify GPR25 as a bona fide CXCL17 receptor and suggest a two-step model of GPR25 activation, in which the receptor N-terminus orients CXCL17 for activation of GPR25 via its C-terminus. We also advocate the reclassification of CXCL17 as a chemoattractant distinct from the chemokine family.
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Journal articleGardiner LE, Lozano-Rojas D, Smith N, et al., 2026, , Int J Infect Dis, Vol: 168
BACKGROUND: Preexisting multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how preexisting MLTCs, including different categorization and patterns of MLTCs, affect 1-year health outcomes after severe COVID-19. METHODS: Adults post-hospitalization after COVID-19 were recruited during 2020-2021. We compared recovery at 1 year after discharge using adjusted multivariable logistic regression in 1:1 propensity-matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without preexisting MLTCs. In adults with MLTCs, different categorization such as number of conditions, number and types of body systems involved (e.g. respiratory, cardiovascular), and latent class analysis-derived patterns of condition co-occurrence were assessed for their association with recovery at 1 year. RESULTS: A total of 647 adults with MLTCs were matched with 647 adults without MLTCs (n = 1294; 61.9% male, 79.6% of White ethnicity, median age 59 [interquartile range 52-67] years). The presence of MLTCs was associated with lower odds of feeling fully recovered (odds ratio 0.66 [95% confidence interval 0.51-0.85], P = 0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g. respiratory [odds ratio 0.49 (95% confidence interval 0.34-0.69), P <0.001]) but not by the number of conditions (P >0.1). Four latent classes of MLTC co-occurrence were estimated with different risks of recovery (P <0.01). CONCLUSION: Adults with preexisting MLTCs were 34% less likely to feel fully recovered at 1 year after COVID-19 hospitalization than adults without MLTCs. We describe prognostic classifications of MLTCs, with future work needed to understand whether they have prognostication in broader post-acute infection sequalae.
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Journal articleBilska AG, Chaszczewska-Markowska M, Gajdanowicz P, et al., 2026, , Ecotoxicol Environ Saf, Vol: 322
Plastics continuously fragment into micro- and nanoplastics (MPs/NPs), which are increasingly recognized as emerging environmental contaminants of global concern. Human exposure to nanoplastics through air, food, and water is becoming unavoidable; however, their direct effects on human immune cells remain poorly understood. Due to their small size, NPs can enter the circulation and directly interact with immune cells, yet their cellular effects in humans remain poorly understood. In this study, we investigated the impact of polystyrene NPs on human peripheral blood mononuclear cells (PBMCs) using an integrated approach that combined imaging, mitochondrial stress testing, basophil activation assays, and single-cell RNA sequencing. Confocal microscopy confirmed efficient cytoplasmic internalization of 25-nm NPs. Optical diffraction tomography revealed that even short-term (1 h) exposure induced pronounced biophysical remodeling, including reduced cell volume and dry mass alongside increased intracellular density and refractive index. Seahorse metabolic profiling demonstrated substantial suppression of mitochondrial respiration across major immune subsets, reflected in reduced basal and maximal respiration, ATP-linked oxygen consumption, and spare respiratory capacity. Basophil activation remained unaffected by NP exposure. Single-cell transcriptomics identified a distinct NP-induced "stress-cell" population, characterized by upregulation of heat-shock and proteostasis pathways and concomitant downregulation of mitochondrial-encoded transcripts. Together, these data show that NPs rapidly disrupt mitochondrial function and activate proteotoxic stress programs in human immune cells. By situating these mechanisms within the One Health framework (human, animal and the planet health), our findings highlight how environmental nanoplastic pollution may translate into immune dysregulation and inform integrated environmental-public health risk assessments.
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Journal articleSakamachi Y, Wiley E, Trempus CS, et al., 2026, , Sci Transl Med, Vol: 18
Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.
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Journal articleNguyen TH, Akdis C, Baccarelli A, et al., 2026, , Allergy
Artificial intelligence (AI) in environmental health science is revolutionizing data analysis and problem-solving approaches. These technologies facilitate the prediction of environmental exposures and disease outcomes and enable the identification of causal relationships for subsequent hypothesis testing. AI techniques improve pollution research through the analysis of satellite imagery and the modeling of pollutant dispersion, while AI advances chemical safety evaluations in toxicology by examining extensive datasets. AI is instrumental in addressing pressing environmental challenges, including remediation of polluted sites and ensuring equitable healthcare applications to mitigate biases. The expanding availability of large-scale environmental, geospatial, and health outcome databases offers unprecedented opportunities for innovative applications. Their predictive capabilities are essential in disaster management, enabling real-time analysis and optimizing resource deployment amid climate-related crises. AI-driven approaches play a critical role in carbon capture and waste management efforts aimed at reducing environmental impact. Furthermore, AI can elucidate complex relationships between the exposome-defined as the totality of exposures throughout an individual's life-and health outcomes, facilitating preventative strategies. This review examines the capabilities and limitations of AI in environmental health and safety, providing insights into its judicious and effective use for environmental management and healthcare.
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Journal articleKonstantinidi R, Yates L, Lloyd C, et al., 2026, , Biology Open, Vol: 15, ISSN: 2046-6390
Primary human basal bronchial epithelial cells (HBECs) are an important population of progenitor cells capable of self-renewal and differentiation to maintain airway homeostasis. At air-liquid interface (ALI) culture, HBECs undergo mucociliary differentiation, providing a robust physiologic model to evaluate novel therapeutics such as in vitro transcribed messenger RNA (IVT-mRNA). However, the impact of IVT-mRNA delivery on the differentiation potential of basal HBECs remains poorly characterised. Poly (beta amino) ester (PBAE) nanoparticles have demonstrated effective airway delivery of IVT-mRNA in various pre-clinical studies. Here, we aimed to understand the impact of PBAE-mediated mRNA transfection on basal HBEC differentiation at ALI. We investigated IVT-mRNA encoding the ciliogenesis transcription factor Forkhead box J1 (FOXJ1) as a model tool for transient overexpression in primary basal HBECs and characterised its subsequent impact on epithelial integrity and differentiation at ALI. PBAE-mediated delivery of FOXJ1 mRNA to submerged primary HBECs resulted in approximately 50% FOXJ1-positive cells and transient upregulation of key ciliogenesis-related genes, including DNALI1 and RSPH9. Following 28 days of differentiation at ALI, FOXJ1 or reporter mRNA transfected cultures displayed normal epithelial morphology, with tight junction and differentiation markers, proportions of secretory and ciliated cells, and cilia ultrastructure comparable to non-transfected controls. These data indicate that PBAE-mediated IVT-mRNA delivery can transiently increase encoded protein expression in basal primary HBECs, without impeding mucociliary differentiation.
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Journal articleArasi S, Bärhold F, Alvaro-Lozano M, et al., 2026, , Allergy, Vol: 81, Pages: 2233-2235
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Journal articleCustovic D, Custovic A, Gern J, et al., 2026, , J Allergy Clin Immunol, Vol: 157, Pages: 1479-1480
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Journal articleVieira RJ, Sousa-Pinto B, Bousquet J, et al., 2026, , Allergy, Vol: 81, Pages: 1947-1970
BACKGROUND: Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. METHODS: The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. RESULTS: Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. CONCLUSION: This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.
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Journal articleUllah A, Fontanella S, Granell R, et al., 2026,
Joint modelling of wheeze and lung function from childhood to early adulthood: four population-based birth cohorts
, EClinicalMedicine, ISSN: 2589-5370Background: Wheeze and lung function (LF) during childhood are key indicators of respiratory health, yet their trajectories are usually examined separately. We aimed to identify joint developmental patterns of wheeze and LF.Methods: We used data from four unselected birth cohorts established between 1989 and 1996 with repeated assessments of wheeze from infancy and spirometry from early school-age to early adulthood. We used group-based multi-trajectory modelling to derive trajectories based on joint modelling of current wheeze and forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC).Findings: In the discovery analysis (n=4,645), we identified 6 trajectories: (1) Never/infrequent wheeze with normal LF (NIFW-NLF, 2925/4645 [62.97%]); (2) Never/infrequent wheeze with reduced LF (NIFW-RLF, 475/4645 [10.22%]); (3) Early-transient wheeze with normal LF (ETW-NLF, 559/4645 [12.03%]); (4) Late-onset wheeze with NLF (LOW-NLF, 335/4645 [7.21%]); (5) Persistent wheeze with NLF (PEW-NLF, 202/4645 [4.34%]); and (6) PEW with RLF (PEW-RLF, 149/4645 [3.21%]). Risk profiles of two trajectories characterised by persistent wheeze but differentiated by normal or reduced LF differed significantly. Elevated fractional exhaled nitric oxide (FeNO) and allergic sensitisation were highly prevalent in both, but only PEW-RLF was significantly associated with perinatal and early-life factors/exposures (prematurity; lower gestational age: RRRs [95% CI] 2.21 [1.49–3.28], low birth weight: 2.60 [1.47–4.60]: and exposure to smoking during gestation: 2.00 [1.49–2.63]). Two low lung function trajectories (with and without symptoms; PEW-RLF and NIFW-RLF) had similar LF impairment, but divergent clinical and risk factor profiles. PEW-RLF was associated with high rates of asthma diagnosis, high FeNO, bronchodilator reversibility, and family history of atopy. In contrast, those in NIFW-RLF trajectory had no elevation in inflammatory biomarkers and low prevalence o
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Journal articleSaunders LC, Collier GJ, Smith LJ, et al., 2026, , J Magn Reson Imaging
BACKGROUND: It is unclear how lung function may recover in patients with residual lung abnormalities (RLAs) following COVID-19 pneumonia. PURPOSE: To evaluate lung function trends over time in patients with RLAs following hospitalization due to COVID-19. STUDY TYPE: Prospective, multicenter longitudinal cohort study. POPULATION: Twenty-four participants hospitalized due to COVID-19 with RLAs identified on CT ≥ 3 months postdischarge (median [IQR] age 69 (15) years; 3 female) underwent at least one MRI at 6 months (n = 16), 1 year (n = 19), or 2 years (n = 14). FIELD STRENGTH/SEQUENCE: 1.5 T. Dynamic contrast enhanced (DCE) 3D spoiled gradient echo, 129Xe steady state free precession (ventilation), 129Xe 3D spoiled gradient echo multiple b-value (diffusion-weighted), 129Xe 4-echo flyback 3D radial (dissolved phase). ASSESSMENT: Pulmonary blood flow, volume, and mean transit time (MTT) were calculated from DCE MRI. The fraction of 129Xe signal in the red blood cells to membrane (RBC:M) was calculated from the dissolved phase 129Xe acquisition. Ventilation defect percentage (VDP) was calculated from the 129Xe ventilation acquisition. Mean diffusive length scale (LmD) was calculated from the 129Xe diffusion-weighted acquisition. STATISTICAL TESTS: Changes in metrics with time and associations between metrics were assessed using mixed-effect linear regression. Correlations were tested using Spearman's correlation coefficient. Regional differences were assessed using a Friedman's test with a Bonferroni adjustment. p < 0.05 was considered significant. RESULTS: Pulmonary blood flow and MTT improved significantly over time (MTT: 6 months, 15.3 (IQR, 2.0); 1 year, 15.6 (1.4); 2 years, 15.0 (5.3); pulmonary blood flow: 6 months, 75.4 (IQR, 22.0); 1 year, 83.2 (47.4); 2 years, 107.3 (51.1)). RBC:M z-score was low at all three visits (
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Journal articleQuammie S, Rashid A, Munyal R, et al., 2026, , BMJ Open Gastroenterol, Vol: 13, ISSN: 2054-4774
OBJECTIVE: Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease associated with increased comorbidity and mortality. This study aimed to characterise the natural history of CP by assessing comorbidity prevalence and mortality in a CP cohort. METHODS: A retrospective cohort study was performed at Nottingham University Hospitals NHS Trust, including patients diagnosed with CP between 1 January 2006 and 31 December 2014. Participants were followed up until 31 May 2023. Comorbidity prevalence was compared with national data from England in 2022 to calculate standardised prevalence ratios (SPRs). Similarly, standardised mortality ratios (SMRs) were also evaluated. RESULTS: Of the 1003 patients with CP, 678 who resided within the Greater Nottingham area were included in the study cohort. The overall median follow-up was 5.7 years (IQR 1.2-10.6). Compared with the general population, patients with CP had significantly elevated SPRs for heart failure (3.0; 95% CI 2.3 to 3.8), diabetes mellitus (2.4; 95% CI 2.1 to 2.7), ischaemic heart disease (2.4; 95% CI 2.0 to 2.8), atrial fibrillation (1.9; 95% CI 1.5 to 2.3) and cerebrovascular disease (1.4; 95% CI 1.0 to 1.8). The cumulative incidence at 20 years of diabetes mellitus, chronic liver disease and chronic kidney disease was 12%, 11% and 11%, respectively. During follow-up, 495 patients (73%) died, with median survival of 5.7 years (95% CI 4.8 to 6.4). The overall SMR of patients with CP was significantly increased (2.3; 95% CI 2.1 to 2.6; p<0.0001) compared with the general population. Leading causes of death were malignancy (27%), infections (22%) and cardiovascular disease (6.9%). CONCLUSION: CP is associated with increased risk of multiple comorbidities and elevated mortality as compared with the general population. Enhanced surveillance and early intervention strategies may help prevent or delay the onset of these associated conditions.
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Journal articleChin D, Hernandez-Beeftink T, Donoghue L, et al., 2026, , Eur Respir J
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Journal articlePerikleous A, Bowen S-J, Griffiths C, et al., 2026, , ERJ Open Research, Vol: 12, ISSN: 2312-0541
BackgroundEosinophilic airway inflammation predicts asthma attacks and inhaled corticosteroid (ICS) response in adults; similar mechanisms may apply to preschool wheeze. This study assessed whether blood eosinophil count (BEC) alone or combined with allergic sensitisation and fractional exhaled nitric oxide (FENO) was associated with future wheeze attacks.Methods95 preschool children (12–59 months old) with clinician-confirmed wheeze were recruited from primary and secondary care. At baseline, finger-prick BEC, skin-prick testing for allergic sensitisation and offline FENO were performed. Children were followed for 8–9 months. The primary outcome was the number of acute wheeze attacks diagnosed during unscheduled visits to an emergency department or general practitioner, documented by parental reports, medical records or oral corticosteroid prescriptions. Exploratory analyses examined ICS association with wheeze attack odds across different biomarker subgroups.ResultsChildren with BEC ≥300 cells·μL−1 had higher wheeze attack odds over 9 months (n=60, odds ratio (OR) 4.27, 95% confidence interval (CI) 1.7–11.38). Odds were greatest in those with BEC ≥300 cells·μL−1 and FENO ≥10 ppb (n=12, OR 60.74, 95% CI 2.98–1238.9). ICS prescription was associated with reduced 3-month wheeze attack odds among children with elevated BEC (n=21, OR 0.11, 95% CI 0.02–0.49) or allergic sensitisation (n=19, OR 0.11, 95% CI 0.01–0.65), with further reduction when both were combined (n=10, OR 0.06, 95% CI 0.002–0.59).ConclusionElevated BEC may identify preschool children at increased wheeze attack odds, particularly when combined with FENO. ICS treatment was associated with odds reduction in children with elevated BEC or allergic sensitisation. These findings provide a rationale for future randomised controlled trials comparing biomarker-guided and symptom-based treatment strategies.
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Journal articlede Benedictis FM, Beasley R, Pavord I, et al., 2026, , Lancet Respir Med
Inhaled corticosteroids are the foundation of asthma therapy and now, 50 years on from their introduction, is an appropriate time to summarise some of the key studies that have progressed the field. We can now make better decisions in selecting the optimal inhaled corticosteroid-based regimens and identifying likely responders, based on biomarkers and patient characteristics. Inhaled corticosteroids reduce the risk of asthma attacks, but do not alter the course of the disease. Asthma remission, which is as yet an undefined therapeutic goal, is the aim, but the role of inhaled corticosteroids is unclear. High-dose inhaled corticosteroid therapy can cause systemic adverse events, suggesting that steps be taken to avoid this through the addition of long-acting β2-adrenergic agonists and the judicious use of biologics. Researchers will continue to learn more about the advantages and limitations of inhaled corticosteroids as they explore methods of disease prevention and remission in the future with new tools and treatments.
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Journal articleOgbogu PU, Roufosse F, Akuthota P, et al., 2026, , Nat Med
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Journal articleSousa-Pinto B, Vieira RJ, Gil-Mata S, et al., 2026, , Allergy
BACKGROUND: To achieve adequate symptom control, patients with allergic rhinitis (AR) often need to increase their medication dose or add other treatments (co-medication). We aimed to perform a systematic review to compare the efficacy and safety of AR medications for increased dose versus co-medication. METHODS: We searched four bibliographic databases and three trial databases for randomised controlled trials assessing the effect of intranasal and/or oral medications in patients of all ages with seasonal or perennial AR. We performed pairwise meta-analysis based on direct evidence to compare (i) non-standard versus standard treatment doses, and (ii) co-medication strategies versus monotherapy using standard doses. Furthermore, we fitted dose-response network meta-analysis (NMA) to obtain projected estimates for comparisons involving two times the standard dose of AR medications in monotherapy versus co-medication with the standard dose of the same medications. We assessed the certainty of evidence using GRADE for NMA. RESULTS: We included 262 studies. Co-medication schemes involving oral antihistamines (OAH) + intranasal corticosteroids (INCS) resulted in higher improvements of nasal symptoms and quality of life than doubling the dose of OAH. However, doubling the dose of intranasal medications led to better results than having intranasal medications + OAH. Doubling the dose of INCS was associated with higher efficacy than adding intranasal antihistamines (INAH). No relevant safety differences were found between treatment strategies. CONCLUSIONS: Results favoured (i) doubling the dose of intranasal medications versus adding OAH, and (ii) adding INCS to OAH over doubling the dose of OAH. This study will inform the ARIA-EAACI 2024-2025 guidelines.
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Journal articleJenkins RG, 2026, , Nat Immunol, Vol: 27, Pages: 890-891
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Journal articleMarques-Mejias A, Bartha I, Ciaccio CE, et al., 2026, , Ann Allergy Asthma Immunol, Vol: 136
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