Publications

The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary. 

If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form

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Publication: Nature Communications

Sungsam Gong, Francesca Gaccioli, Justyna Dopierala, Ulla Sovio, Emma Cook, Pieter-Jan Volders, Lennart Martens, Paul D. W. Kirk, Sylvia Richardson, Gordon C. S. Smith & D. Stephen Charnock-Jones 

11 May 2021


Summary

The placenta is understudied and is commonly omitted from large-scale “-omic” analyses, this study enables tissue-wide comparison of transcriptome analyses, looking at identification placentally-related adverse pregnancy outcomes such as fetal growth restriction (FGR) and preeclimisia (PE).

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Publication: Science

Josephine M. Bryant,  Karen P. Brown,  Sophie Burbaud,  Isobel Everall,  Juan M. Belardinelli, Daniela Rodriguez-Rincon,  Dorothy M. Grogono,  Chelsea M. Peterson,  Deepshikha Verma,  Ieuan E. Evans,  Christopher Ruis,  Aaron Weimann,  Divya Arora,  Sony Malhotra,  Bridget Bannerman, Charlotte Passemar,  Kerra Templeton,  Gordon MacGregor, Kasim Jiwa,  Andrew J. Fisher,  Tom L. Blundell,  Diane J. Ordway,  Mary Jackson, Julian Parkhill, R. Andres Floto

30 April 2021


Summary:

Researchers have been able to track how a multi-drug resistant organism is able to evolve and spread widely among cystic fibrosis patients – showing that it can evolve rapidly within an individual during chronic infection. The researchers say their findings highlight the need to treat patients with Mycobacterium abscessus infection immediately, counter to current medical practice.

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Publication: bioRxiv

Conde C Domínguez, T Gomes, LB Jarvis, C Xu, SK Howlett, DB Rainbow, O Suchanek, HW King, L Mamanova, K Polanski, N Huang, E Fasouli, KT Mahbubani, M Prete, L Campos, HS Mousa, EJ Needham, S Pritchard, T Li, R Elmentaite, J Park, DK Menon, OA Bayraktar, LK James, KB Meyer, MR Clatworthy, K Saeb-Parsy, JL Jones, SA Teichmann

28 April 2021


Summary

Despite their crucial role in health and disease, researchers knowledge of immune cells within human tissues, in contrast to those circulating in the blood, remains limited. Researchers surveyed the immune compartment of lymphoid and non-lymphoid tissues of six adult donors by single-cell RNA sequencing, including alpha beta T-cell receptor, gamma delta TCR and B-cell receptor variable regions.

To aid systematic cell type identification researchers developed CellTypist, a tool for automated and accurate cell type annotation. Using this approach combined with manual curation, researchers determined the tissue distribution of finely phenotyped immune cell types and cell states.

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Publication: American Journal of Obstetrics and Gynecology

Ulla Sovio, Francesca Gaccioli, Emma Cook, Stephen Charnock-Jones, .Gordon C.S,

24 April 2021


Summary

Slowing of fetal growth and elevated maternal serum are associated with early term spontaneous labor

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Publication: Nature

Emily Stephenson, Gary Reynolds, Rachel A. Botting, Fernando J. Calero-Nieto, Michael D. Morgan, Zewen Kelvin Tuong, Karsten Bach, Waradon Sungnak, Kaylee B. Worlock, Masahiro Yoshida, Natsuhiko Kumasaka, Katarzyna Kania, Justin Engelbert, Bayanne Olabi, Jarmila Stremenova Spegarova, Nicola K. Wilson, Nicole Mende, Laura Jardine, Louis C. S. Gardner, Issac Goh, Dave Horsfall, Jim McGrath, Simone Webb, Michael W. Mather, Rik G. H. Lindeboom, Emma Dann, Ni Huang, Krzysztof Polanski, Elena Prigmore, Florian Gothe, Jonathan Scott, Rebecca P. Payne, Kenneth F. Baker, Aidan T. Hanrath, Ina C. D. Schim van der Loeff, Andrew S. Barr, Amada Sanchez-Gonzalez, Laura Bergamaschi, Federica Mescia, Josephine L. Barnes, Eliz Kilich, Angus de Wilton, Anita Saigal, Aarash Saleh, Sam M. Janes, Claire M. Smith, Nusayhah Gopee, Caroline Wilson, Paul Coupland, Jonathan M. Coxhead, Vladimir Yu Kiselev, Stijn van Dongen, Jaume Bacardit, Hamish W. King, Anthony J. Rostron, A. John Simpson, Sophie Hambleton, Elisa Laurenti, Paul A. Lyons, Kerstin B. Meyer, Marko Z. Nikolić, Christopher J. A. Duncan, Kenneth G. C. Smith, Sarah A. Teichmann, Menna R. Clatworthy, John C. Marioni, Berthold Göttgens & Muzlifah Haniffa

20 April 2020


Summary

A UK-wide study has identified differences in people’s immune responses to COVID-19, depending on whether they have no symptoms or more serious reactions to the virus. Read the full story

 

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Publication: Ultrasound in Obstetrics and Gynecology

F. Mone,  R. Y. Eberhardt, M. E. Hurles,  D. J. McMullan,  E. R. Maher,  J. Lord,  L. S. Chitty,  E. Dempsey,  T. Homfray,  J. L. Giordano,  R. J. Wapner,  L. Sun, T. N. Sparks,  M. E. Norton, M. D. Kilby

13 April 2021


Summary

Use of prenatal next generation sequencing in both isolated and non‐isolated NIHF should be considered in developing clinical pathways.

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Publication: Revista de Psiquiatría y Salud Mental

Alabaf S, Kirkpatrick B, Chen S, Cardinal RN, Fernández-Egea E

10 April 2021


Schizophrenia typically involves so-called “positive” or psychotic symptoms (symptoms that are present but are unwanted), but sometimes also so-called “negative” or deficit symptoms (aspects of normal behaviour that are absent).

In a group of 167 patients with schizophrenia and being treated with clozapine, those patients with “non-deficit” schizophrenia were more likely than those with “deficit” schizophrenia to have reported cannabis use by the time of their first-episode psychosis, or trauma (related to crime or abuse) prior to that first episode of psychosis.

Patients with “deficit” schizophrenia were more likely to have been born in summer months. The timing of stressors during brain development may influence the pattern of symptoms that emerge.

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Publication: Brain

Claire O’Callaghan, Frank H Hezemans, Rong Ye, Catarina Rua, P Simon Jones, Alexander G Murley, Negin Holland, Ralf Regenthal, Kamen A Tsvetanov, Noham Wolpe, Roger A Barker, Caroline H Williams-Gray, Trevor W Robbins, Luca Passamonti, James B Rowe

30 March 2021


Summary:

Drugs that increase the brain’s noradrenaline can improve cognition in Parkinson’s disease. A challenge remains to identify those who will most benefit from noradrenergic drugs. We show that drug response depends on integrity of the locus coeruleus nucleus. This will inform clinical trial patient selection and treatment.

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Publication: NeuroImage: Clinical

Martina Bocchetta, Emily G. Todd, Georgia Peakman, David M. Cash, Rhian S. Convery, Lucy L.Russell, David L. Thomas, Juan Eugenio Iglesias, John C.van Swieten, Lize C. Jiskootf, Harro Seelaar, Barbara Borronig, Daniela Galimbertihi, Raquel Sanchez-Vallej, Robert Laforce Jr, Fermin Morenol, Matthis Synofzik, Caroline Graffno, Mario Masellis, Maria Carmela Tartaglia, James B.Rower, Rik Vandenberghes, Elizabeth, Finger, Fabrizio Tagliaviniu, Alexandrede Mendonçav, Isabel Santanaw, Chris R.Butlerx, Simon Ducharmey, Alexander Gerhardza,  AdrianDanek, JohannesLevina,  Markus Ottoac, Sandro Sorbiad, Isabelle Le Beraeafag, Florence Pasquierahaiaj, Jonathan D.Rohrera.

29 March 2021


Summary

Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups.

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Publication: The Lancet Psychiatry

Varun Warrier, Alex S F Kwong, Mannan Luo, Shareefa Dalvie, Jazz Croft, Hannah M Sallis, et al.

16 March 2021


Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, the researchers aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health.

They did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank, Psychiatric Genomics Consortium, Avon Longitudinal Study of Parents and Children, Adolescent Brain Cognitive Development Study and Generation R.

Family-based and population-based polygenic score analyses were done to elucidate gene–environment correlation mechanisms. The team used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions.

This meta-analysis of genome-wide association studies identified 14 independent loci associated with childhood maltreatment. The researchers identified high genetic overlap among different maltreatment operationalisations, subtypes, and reporting methods.

Within-family analyses provided some support for active and reactive gene–environment correlation but did not show the absence of passive gene–environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration).

Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment.

Family-based analyses point to a role of active and reactive gene–environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. This study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects.

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Publication: International Journal of Epidemiology

Aurora Perez-Cornago , Francesca L Crowe, Paul N Appleby, Kathryn E Bradbury, Angela M Wood, Marianne Uhre Jakobsen, Laura Johnson, Carlotta Sacerdote, Marinka Steur, Elisabete Weiderpass, Anne Mette L Würtz, Tilman Kühn, Verena Katzke, Antonia Trichopoulou, Anna Karakatsani, Carlo La Vecchia, Giovanna Masala, Rosario Tumino, Salvatore Panico, Ivonne Sluijs, Guri Skeie, Liher Imaz, Dafina Petrova, J Ramón Quirós, Sandra Milena Colorado Yohar, Paula Jakszyn, Olle Melander, Emily Sonestedt, Jonas Andersson, Maria Wennberg, Dagfinn Aune, Elio Riboli, Matthias B Schulze, Emanuele di Angelantonio, Nicholas J Wareham, John Danesh, Nita G Forouhi, Adam S Butterworth, Timothy J Key

3 March 2021


Summary

Epidemiological evidence indicates that diets rich in plant foods are associated with a moderately lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre.

This study found that higher intakes of fruit and vegetables combined, total fruit, bananas, nuts and seeds, total fibre, fruit and vegetable combined fibre and fruit fibre are associated with a lower risk of IHD, of small magnitude.

To the best of the researchers’ knowledge, this is the largest prospective study looking at major plant foods, their subtype, and dietary fibre in relation to IHD risk including incident IHD cases and death from IHD.

As with other observational studies, the associations reported may be subject to residual confounding, and whether these small associations are causal remains unclear.

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Publication: European Journal of Epidemiology

Stephen Burgess, Sonja A Swanson & Jeremy A Labrecque

21 February 2021


Mendelian randomization uses genetic variants as instrumental variables to make causal inferences about the effect of a risk factor on an outcome. If a genetic variant satisfies the instrumental variable assumptions for the given risk factor and outcome, then an association between the genetic variant and the outcome implies the risk factor affects the outcome in some individuals at some point in the life-course.

Combining the instrumental variable assumptions with further assumptions and precise specification of the outcome (including specifying a time period for the outcome) allows valid testing of a more specific causal hypothesis and/or valid estimation of global or local, and point or period average causal effects.

In this short manuscript, the researchers discuss three ways in which Mendelian randomization analyses may be susceptible to bias due to reverse causation. They conclude that while the analyses offer some protection against biases, they are not totally immune from the phenomenon; and that researchers should consider carefully whether their findings could be explained by genetic variants having a primary association with the outcome, and how previous versions of an outcome can impact the stated risk factor.

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