EBioMedicine

Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses
Einhauser S, Asam C, Weps M, Senninger A, Peterhoff D, Bauernfeind S, Asbach B, Carnell GW, Heeney JL, Wytopil M, Fuchs A, Messmann H, Prelog M, Liese J, Jeske SD, Protzer U, Hoelscher M, Geldmacher C, Überla K, Steininger P, Wagner R and
The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study.
Genomic insights for personalised care in lung cancer and smoking cessation: motivating at-risk individuals toward evidence-based health practices
Chen T, Pham G, Fox L, Adler N, Wang X, Zhang J, Byun J, Han Y, Saunders GRB, Liu D, Bray MJ, Ramsey AT, McKay J, Bierut LJ, Amos CI, Hung RJ, Lin X, Zhang H and Chen LS
Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes.
A substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity
Li Y, Zhang X, Tai W, Zhuang X, Shi H, Liao S, Yu X, Mei R, Chen X, Huang Y, Liu Y, Liu J, Liu Y, Zhu Y, Wang P, Tian M, Yu G, Li L and Cheng G
Global dissemination of SARS-CoV-2 Omicron sublineages has provided a sufficient opportunity for natural selection, thus enabling beneficial mutations to emerge. Characterisation of these mutations uncovers the underlying machinery responsible for the fast transmission of Omicron variants and guides vaccine development for combating the COVID-19 pandemic.
Physical inactivity exacerbates pathologic inflammatory signalling at the single cell level in patients with systemic lupus
Patterson SL, Van Phan H, Ye CJ, Lanata C, González SC, Park J, Criswell LA, Barbour KE, Yazdany J, Dall'Era M, Sirota M, Katz P and Langelier CR
Physical activity is an adjunctive therapy that improves symptoms in people living with systemic lupus erythematosus (SLE), yet the mechanisms underlying this benefit remain unclear.
Evolving vaccine discovery and development pathways for emerging pathogens
St John AL and Ooi EE
Development and evaluation of an antigen targeting lateral flow test for Crimean-Congo Haemorrhagic Fever
Thompson CR, Bozkurt I, Cosgun Y, Blundell P, Duvoix A, Johnson M, Hedef H, Arslan FG, Umudum BA, Bilek HC, Tanyel E, Pektaş AN, Taşseten TN, Bakir M, Büyüktuna SA, Olçar Y, Yilmaz FA, Arslan M, Al-Hilfi RA, Hasan HA, Khaleel RI, Aufi IM, Mahdi SG, Aakef IR, Shakir HA, Hussein AA, Abdulhadi NA, Mohsin ZA, Korukluoglu G, Cubas Atienzar AI, Fletcher TE and Adams E
Crimean-Congo Haemorrhagic Fever (CCHF) is a viral haemorrhagic fever with a case fatality rate of 5-25% that has been prioritised for research and development by the World Health Organisation. There are no CCHF rapid diagnostic tests (RDTs) commercially available. We describe the development and evaluation of an antigen-targeting lateral flow immunoassay RDT for CCHF.
Development of a deep learning algorithm for Paneth cell density quantification for inflammatory bowel disease
Kang LI, Sarullo K, Marsh JN, Lu L, Khonde P, Ma C, Haritunians T, Mujukian A, Mengesha E, McGovern DPB, Stappenbeck TS, Swamidass SJ and Liu TC
Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation. Our aim was to use DL to quantify PCs for use as a quantitative biomarker.
Molecular imaging in experimental pulmonary fibrosis reveals that nintedanib unexpectedly modulates CCR2 immune cell infiltration
Farooq H, Luehmann HP, Koenitzer JR, Heo GS, Sultan DH, Kulkarni DH, Gunsten SP, Sashti RM, Huang T, Keller AR, Lavine KJ, Atkinson JJ, Wingler LM, Liu Y and Brody SL
Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.
A decade of discovery: bridging science and clinical practice in biomedical research
eBioMedicine
Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants
Chong SMY, Hung RKY, Yuen Chang F, Atkinson C, Fernando R, Harber M, Magee CN, Salama AD and Reeves M
BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical.
Cross-sectional and longitudinal genotype to phenotype surveillance of SARS-CoV-2 variants over the first four years of the COVID-19 pandemic
Akerman A, Fichter C, Milogiannakis V, Esneau C, Silva MR, Ison T, Lopez JA, Naing Z, Caguicla J, Amatayakul-Chantler S, Roth N, Manni S, Hauser T, Barnes T, Boss T, Condylios A, Yeang M, Sato K, Bartlett NN, Darley D, Matthews G, Stark DJ, Promsri S, Rawlinson WD, Murrell B, Kelleher AD, Dwyer D, Sintchenko V, Kok J, Ellis S, Marris K, Knight E, Hoad VC, Irving DO, Gosbell I, Brilot F, Wood J, Aggarwal A and Turville SG
Continued phenotyping and ongoing molecular epidemiology are important in current and future monitoring of emerging SARS-CoV-2 lineages. Herein we developed pragmatic strategies to track the emergence, spread and phenotype of SARS-CoV-2 variants in Australia in an era of decreasing diagnostic PCR testing and focused cohort-based studies. This was aligned to longitudinal studies that span 4 years of the COVID-19 pandemic.
Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study
Nakase H, Wagatsuma K, Kobayashi T, Matsumoto T, Esaki M, Watanabe K, Kunisaki R, Takeda T, Arai K, Ibuka T, Ishikawa D, Matsuno Y, Sakuraba H, Ueno N, Yokoyama K, Saruta M, Hokari R, Yokoyama J, Tamano S, Nojima M, Hisamatsu T and
The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations.
Circadian rhythms in haematological malignancies: therapeutic potential and personalised interventions
Motiei M, Abu-Dawud R, Relógio A and Assaf C
The circadian clock, a fundamental cellular mechanism, regulates the rhythmic expression of numerous genes and biological processes across various organs. Disruptions in this system, driven by genetic or environmental factors, have been reported to be involved in cancer progression. This review explores the role of the circadian clock in cancer hallmarks and its impact on cellular homeostasis within haematological malignancies. Drawing on findings from in vitro, in vivo, and clinical trials, this review highlights the potential of clock genes as diagnostic and prognostic biomarkers, and as therapeutic targets for optimising treatment timing. It discusses how circadian rhythms can enhance treatment efficacy through both pharmacological and non-pharmacological interventions, outlining strategies for optimising dosing schedules and implementing personalised chronobiological interventions, with a particular focus on haematological malignancies, including cutaneous lymphoma. Ongoing research holds promise for advancing personalised therapeutic approaches and ultimately improving cancer care standards.
Generative AI agents are transforming biology research: high resolution functional genome annotation for multiscale understanding of life
Harrer S, Rane RV and Speight RE
Transformer-based deep learning model for the diagnosis of suspected lung cancer in primary care based on electronic health record data
Wang L, Yin Y, Glampson B, Peach R, Barahona M, Delaney BC and Mayer EK
Due to its late stage of diagnosis lung cancer is the commonest cause of death from cancer in the UK. Existing epidemiological risk models in clinical usage, which have Positive Predictive Values (PPV) of less than 10%, do not consider the temporal relations expressed in sequential electronic health record (EHR) data. We aimed to build a model for lung cancer early detection in primary care using machine learning with deep 'transformer' models on EHR data to learn from these complex sequential 'care pathways'.
Which experimental factors govern successful animal-to-human translation in multiple sclerosis drug development? A systematic review and meta-analysis
Berg I, Härvelid P, Zürrer WE, Rosso M, Reich DS and Ineichen BV
Despite successes in multiple sclerosis (MS) drug development, the effectiveness of animal studies in predicting successful bench-to-bedside translation is uncertain. Our goal was to identify predictors of successful animal-to-human translation for MS by systematically comparing animal studies of approved disease-modifying therapies (DMTs) with those that failed in clinical trials due to efficacy or safety concerns.
Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III region
Chen J, Zhang H, Fu T, Zhao J, Nowak JK, Kalla R, Wellens J, Yuan S, Noble A, Ventham NT, Dunlop MG, Halfvarson J, Mao R, Theodoratou E, Satsangi J and Li X
This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms.
Liver SMN restoration rescues the Smn mouse model of spinal muscular atrophy
Sutton ER, Beauvais A, Yaworski R, De Repentigny Y, Reilly A, Alves de Almeida MM, Deguise MO, Poulin KL, Parks RJ, Schneider BL and Kothary R
The liver is a key metabolic organ, acting as a hub to metabolically connect various tissues. Spinal muscular atrophy (SMA) is a neuromuscular disorder whereby patients have an increased susceptibility to developing dyslipidaemia and liver steatosis. It remains unknown whether fatty liver is due to an intrinsic or extrinsic impact of survival motor neuron (SMN) protein depletion.
Multi-omic characteristics of longitudinal immune profiling after breakthrough infections caused by Omicron BA.5 sublineages
Li Y, Qin S, Dong L, Xiao Y, Zhang Y, Hou Y, Qiao S, Zhang R, Li Y, Bao Y, Zhao X, Ma Y and Gao GF
Omicron sub-variants breakthrough infections (BTIs) have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. The acute-phase immune status is critical for prognosis, however, the dynamic immune profiling of COVID-19 during the first month after BTIs remains unclear.
Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies
Moll M, Hecker J, Platig J, Zhang J, Ghosh AJ, Pratte KA, Wang RS, Hill D, Konigsberg IR, Chiles JW, Hersh CP, Castaldi PJ, Glass K, Dy JG, Sin DD, Tal-Singer R, Mouded M, Rennard SI, Anderson GP, Kinney GL, Bowler RP, Curtis JL, McDonald ML, Silverman EK, Hobbs BD and Cho MH
Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.
Screening for depression in the general population through lipid biomarkers
Tkachev A, Stekolshchikova E, Golubova A, Serkina A, Morozova A, Zorkina Y, Riabinina D, Golubeva E, Ochneva A, Savenkova V, Petrova D, Andreyuk D, Goncharova A, Alekseenko I, Kostyuk G and Khaitovich P
Anxiety and depression significantly contribute to the overall burden of mental disorders, with depression being one of the leading causes of disability. Despite this, no biochemical test has been implemented for the diagnosis of these mental disorders, while recent studies have highlighted lipids as potential biomarkers.