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: The American Journal of Clinical Nutrition

Jelisa Gallant, Kathleen Chan, Tim J Green, Frank T Wieringa, Shalem Leemaqz, Rem Ngik, Jeffrey R Measelle, Dare A Baldwin, Mam Borath, Prak Sophonneary, Lisa N Yelland, Daniela Hampel, Setareh Shahab-Ferdows, Lindsay H Allen, Kerry S Jones, Albert Koulman, Damon A Parkington, Sarah R Meadows, Hou Kroeun, Kyly C Whitfield

07 April 2021


Summary

Thiamine (vitamin B1) is essential for normal growth, development and energy metabolism. Thiamine is found in a wide-range of foods and deficiency is not usually a problem with a varied diet. However, in some populations, with diets that consist mostly of thiamine-poor white, polished rice, there may be an increased risk of thiamine deficiency.

The NIHR Cambridge BRC Nutritional Biomarker Laboratory was responsible for the blood analysis of two thiamine biomarkers for a recently published study led by Dr Kyly Whitfield (Mount Saint Vincent University, Canada). The aim of the study was to investigate the amount of supplemental thiamine intake required to optimise breastmilk thiamine concentrations and mother and infant blood thiamine status.

In the study, 335 mothers in rural Cambodia were randomised to one of four daily thiamine supplementation doses (0, 1.2, 2.4, or 10 mg per day) from 2 weeks to 6 months postpartum. At the end of the intervention period, blood samples were collected from mothers and infants, and breastmilk from mothers to estimate the optimal thiamine dose to improve thiamine status.

The results showed that women taking any of the thiamine-containing supplements had significantly higher thiamine content in their milk compared to the placebo group. Both mothers and infants had improved blood thiamine status after supplementation. In the study, a dose of 1.2 mg thiamine/day improved the thiamine status of breastfeeding mothers and their infants, normalising thiamine status, and may reduce the risk of thiamine deficiency and infantile beriberi. We hope the results of this study will inform a future thiamine fortification program in Cambodia, and elsewhere in South and Southeast Asia where thiamine deficiency remains a public health concern.

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Publication: Nature

Ekaterina Yonova-Doing, Claudia Calabrese, Aurora Gomez-Duran, Katherine Schon, Wei Wei, Savita Karthikeyan, Patrick F. Chinnery & Joanna M. M. Howson

17 May 2021


Summary

Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored, partly due to a lack of genotype calling and quality-control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within subpopulations of Great Britain and establish a UK Biobank reference atlas of mtDNA–phenotype associations.

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Publication: Stroke

Segun Fatumo , Ville Karhunen, Tinashe Chikowore, Toure Sounkou , Brenda Udosen, Chisom Ezenwa, Mariam Nakabuye, Opeyemi Soremekun, Iyas Daghlas, David K. Ryan, Amybel Taylor, Amy M. Mason, Scott M. Damrauer, Marijana Vujkovic, Keith L. Keene, Myriam Fornage, Marjo-Riitta Järvelin, Stephen Burgess, Dipender Gill,

3 June 2021


Summary

Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals

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Publication: Proceedings of the National Academy of Sciences (PNAS)

Irene Cimino, Hanna Kim, Y. C. Loraine Tung, Kent Pedersen, Debra Rimmington, John A. Tadross,  Sara N. Kohnke, Ana Neves-Costa, André Barros, Stephanie Joaquim, Don Bennett, Audrey Melvin, Samuel M. Lockhart,  Anthony J. Rostron, Jonathan Scott, Hui Liu,  Keith Burling, Peter Barker, Menna R. Clatworthy, E-Chiang Lee,A. John Simpson, Giles S. H. Yeo, Luís F. Moita, Kendra K. Bence, Sebastian Beck Jørgensen, Anthony P. Coll, Danna M. Breen, and Stephen O’Rahilly

30 June 2021


Summary

Researchers have described a new way that the body senses damage and activates hormones in response to stressful situations – involving the protein GDF15

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Publication: Clinical Trials

Estée Török, Benjamin R Underwood, Mark Toshner, Claire Waddington, Emad Sidhom, Katherine Sharrocks, Rachel Bousfield, Charlotte Summers, Caroline Saunders, Zoe McIntyre, Helen Morris, Jo Piper, Gloria Calderon, Sarah Dennis, Tracy Assari, Anita Marguerie de Rotrou, Ashley Shaw, John Bradley, John O’Brien, Robert C Rintoul, Ian Smith, Ed Bullmore, Krishna Chatterjee

22 June 2021


Summary

Researchers describe their experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom.

Researchers encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. These were overcome by setting up a project team that included key members from all three organisations that met at least daily by teleconference.

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Publication: Cell Reports

Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova

29 June 2021


One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation – the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Researchers led by scientists at the University of Cambridge show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

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Publication: Science Direct

Setareh Alabaf, Brian Kirkpatrick, Shanquan Chenc, Rudolf N. Cardinal, Emilio Fernandez-Egea

28 June 2021


Summary

Researchers examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms.

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Publication: Authorea (pre-print)

Mark Ferris, Rebecca Ferris, Chris Workman, Eoin O’Connor, David A Enoch, Emma Goldesgeyme, Natalie Quinnell, Parth Patel, Jo Wright, Geraldine Martell, Christine Moody, Ashley Shaw, Christopher J.R. Illingworth, Nicholas J. Matheson, Michael P. Weekes

24 June 2021


When Addenbrooke’s Hospital in Cambridge upgraded its face masks for staff working on COVID-19 wards to filtering face piece 3 (FFP3) respirators, it saw a dramatic fall – up to 100% – in hospital-acquired SARS-CoV-2 infections among these staff.

The findings are reported by a team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust. The research has not yet been peer-reviewed, but is being released early because of the urgent need to share information relating to the pandemic.

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Publication: Annals of Clinical and Translational Neurology

Maura Malpetti, , Negin Holland, P. Simon Jones, Rong Ye, , Thomas E. Cope, Tim D. Fryer, Young T. Hong, George Savulich, Timothy Rittman, Luca Passamonti, Elijah Mak, Franklin I. Aigbirhio, John T. O’Brien, & James B. Rowe

16 June 2021


Summary

Brain cells communicate via special connections called synapses. The loss of these synapses is common and early in dementia. We can now measure the amount of synapses across the brain, in people, with a brain scanning technique called positron emission tomography.

Researchers studied healthy adults who were at risk of developing dementia because of a mutation in a gene called C9orf72. They found that synapse loss was already present many years before symptoms were expected, especially in a part of the brain called the thalamus. Such early pre-symptomatic changes are vital to measure, in order to test preventative treatments to step dementia in people at high genetic risk

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Publication: Geriatric Psychiatry

Kathy Y. Liu, Robert Howard, Sube Banerjee, Adelina Comas-Herrera, Joanne Goddard, Martin Knapp, Gill Livingston, Jill Manthorpe, John T. O’Brien, Ross W. Paterson, Louise Robinson, Martin Rossor, James B. Rowe, David J. Sharp, Andrew Sommerlad, Aida Suárez-González, Alistair Burns

16 May 2021


In response to a commissioned research update on dementia during the COVID-19 pandemic, a UK-based working group, comprising dementia researchers from a range of fields and disciplines, aimed to describe the impact of the pandemic on dementia wellbeing and identify priorities for future research.

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Publication: Scientific Reports

Ottaviani JI, Britten A, Lucarelli D, Luben R, Mulligan AA, Lentjes MA, Fong R et al

21 October 2020


Summary

Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, researchers investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort.

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Publication: Nutrients

Haynes E, Bhagtani D, Iese V, Brown CR, Fesaitu J, Hambleton I, Badrie N et al

30 October 2020


Summary

Small Island Developing States (SIDS) have high and increasing rates of diet-related diseases. This situation is associated with a loss of food sovereignty and an increasing reliance on nutritionally poor food imports. A policy goal, therefore, is to improve local diets through improved local production of nutritious foods. Researchers aim in this study was to develop methods and collect preliminary data on the relationships between where people source their food, their socio-demographic characteristics and dietary quality in Fiji and Saint Vincent and the Grenadines (SVG) in order to inform further work towards this policy goal.
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Publication: American Journal of Human Biology

Skottrup P, Kallemose T, Espino D, Infante‐Ramirez R, Brage S, Terzic D et al.

9 September 2020


Summary

Previous studies have suggested that acute exercise-induced cardiac and kidney damage following ultra-distance running is low in Mexican Tarahumara even though C-reactive protein (CRP) remained elevated 24 hours post-race. Researchers aimed to study if the plasma biomarker, soluble urokinase-type plasminogen activator receptor (suPAR), could replace or complement CRP as a systemic inflammation biomarker in Tarahumara men and women following ultra-distance running.

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Publication: PLOS Medicine

Corder K, Sharp S, Jong S, Foubister C, Brown H, Wells E et al.

23 July 2020


Summary

Less than 20% of adolescents globally meet recommended levels of physical activity, and not meeting these recommended levels is associated with social disadvantage and rising disease risk. The determinants of physical activity in adolescents are multilevel and poorly understood, but the school’s social environment likely plays an important role. Researchers conducted a cluster randomised controlled trial to assess the effectiveness of a school-based programme (GoActive) to increase moderate-to-vigorous physical activity (MVPA) among adolescents.

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Publication: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Kanen JW, Arntz FE, Yellowlees R, Price A, Christmas DM, Apergis-Schoute AM, Sahakian BJ, Cardinal RN, Robbins TW

12 January 2021


Summary

Responding emotionally to danger is critical for survival. Normal functioning also requires flexible alteration of emotional responses when a threat becomes safe. Aberrant threat and safety learning occur in many psychiatric disorders, including posttraumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, in which emotional responses can persist pathologically. While there is evidence that threat and safety learning can be modulated by the serotonin systems, there have been few studies in humans. Researchers addressed a critical clinically relevant question: How does lowering serotonin affect memory retention of conditioned threat and safety memory?

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Publication: BMJ Nutrition

Aljuraiban G, Chan Q, Gibson R, Stamler J, Daviglus M, Dyer A et al.

8 July 2020


Summary

Plant-based diets are associated with a lower risk of cardiovascular diseases; however, little is known how the healthiness of the diet may be associated with blood pressure (BP). Researchers aimed to modify three plant -based diet indices: overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) according to country-specific dietary guidelines to enable use across populations with diverse dietary patterns – and assessed their associations with BP.

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Publication: Diabetes Care

Ibsen D, Steur M, Imamura F, Overvad K, Schulze M, Bendinelli B et al.

22 June 2020


Summary

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Publication: Human Molecular Genetics

Mann J, Pietzner M, Wittemans L, Rolfe E, Kerrison N, Imamura F et al.

15 October 2020


Summary

Several genetic discoveries robustly implicate five single-nucleotide variants in the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis and fibrosis (NASH-fibrosis), including a recently identified variant in MTARC1. To better understand these variants as potential therapeutic targets, researchers aimed to characterize their impact on metabolism using comprehensive metabolomics data from two population-based studies

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Publication: BMJ

Zheng J, Sharp S, Imamura F, Chowdhury R, Gundersen T, Steur M et al.

8 July 2020


Summary

Researchers investigated the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

 

 

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Publication: Journal of Physical Activity and Health

Bielemann R, Silveira M, Lutz B, Miranda V, Gonzalez M, Brage S et al.

29 May 2020


Summary

Previous observations regarding association between physical activity (PA) and use of medicines among older adults are derived from self-reported PA. This study aimed to evaluate the association between objectively measured PA and polypharmacy among older adults with multimorbidity in Southern Brazil.

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