The latest list of publications from the 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 the attached form.
Publication: European Respiratory Journal
Anthony W. Martinelli, Tejas Ingle, Joseph Newman, Iftikhar Nadeem, Karl Jackson, Nicholas D. Lane, James Melhorn, Helen E. Davies, Anthony J. Rostron, Aldrin Adeni, Kevin Conroy, Nicholas Woznitza, Matthew Matson, Simon E. Brill, James Murray, Amar Shah, Revati Naran, Samanjit S. Hare, Oliver Collas, Sarah Bigham, Michael Spiro, Margaret M. Huang, Beenish Iqbal, Sarah Trenfield, Stephane Ledot, Sujal Desai, Lewis Standing, Judith Babar, Razeen Mahroof, Ian Smith, Kai Lee, Nairi Tchrakian, Stephanie Uys, William Ricketts, Anant R.C. Patel, Avinash Aujayeb, Maria Kokosi, Alexander J.K. Wilkinson, Stefan J. Marciniak
10 September 2020
Pneumothorax and pneumomediastinum have both been noted to complicate cases of COVID-19 requiring hospital admission. The research team reported the largest case series yet described of patients with both these pathologies that includes non-ventilated patients.
Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival.
Seventy-one patients from 16 centres were included in the study, of whom 60 patients had pneumothoraces (six also with pneumomediastinum), whilst 11 patients had pneumomediastinum alone.
Survival at 28 days was not significantly different following pneumothorax or isolated pneumomediastinum. The incidence of pneumothorax was higher in males. The 28-day survival was not different between the sexes. Patients above the age of 70 had a significantly lower 28-day survival than younger individuals.
These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and the researchers encourage active treatment to be continued where clinically possible.
Anthony Martinelli and Margaret Huang are supported by the Wellcome Trust. Stefan Marciniak is supported by the Medical Research Council, NIHR Cambridge BRC, Royal Papworth Hospital and the Alpha1-Foundation.View publication
Publication: Nature Medicine
Sarah Killcoyne, Eleanor Gregson, David C. Wedge, Dan J. Woodcock, Matthew D. Eldridge, Rachel de la Rue, Ahmad Miremadi, Sujath Abbas, Adrienn Blasko, Cassandra Kosmidou, Wladyslaw Januszewicz, Aikaterini Varanou Jenkins, Moritz Gerstung & Rebecca C. Fitzgerald
07 September 2020
Barrett’s oesophagus is a risk factor for oesophageal cancer. The oesophagus or known as the gullet or food pipe, connects from your mouth to the stomach. Cells within the oesophagus can change and become abnormal. Biopsies taken via an endoscopy can help detect any abnormal cells.
Oesophageal cancer can be hard to detect, Cambridge researchers investigated whether patients could be identified earlier. Using DNA tissue biopsies from patients diagnosed with Barrett’s oesophagus could show which patients are more likely to develop the disease.
Using whole genome sequencing, researchers analysed samples from 88 patients and compared their DNA against control samples collected during clinical surveillance for Barrett’s oesophagus. Researchers looked at the differences in the DNA between patients who were eventually diagnosed with cancer to those who were not. They found several changes and used this model to predict whether a patient was at a high or low risk of cancer.
They found the model could correctly predict oesophageal cancer eight years before diagnosis for half of all patients who went on to develop the disease. This increased to more than three-quarters of patients one to two years before a diagnosis. Read the full story.View publication
Publication: JCO Clinical Cancer Informatics
Mireia Crispin-Ortuzar, Marcel Gehrung, Stephan Ursprung, Andrew B. Gill, Anne Y. Warren, Lucian Beer, Ferdia A. Gallagher, Thomas J. Mitchell, Iosif A. Mendichovszky, Andrew N. Priest, Grant D. Stewart, Evis Sala, Florian Markowetz
Cancer is a highly heterogeneous disease. Different parts of a single tumour often look different in medical images; they sometimes even carry different genetic information. This complexity may be key to understanding why some tumours respond better to therapy than others. Once the tumour has been removed through surgery, researchers can obtain tissue samples that allow them to study its spatial composition. However, matching these data to the images that were obtained before surgery is challenging.
The research team developed a computational methodology that relies on 3D printing to automatically design and create tumour moulds that help to match images and tissue accurately without disrupting clinical practice.
Their work provides a robust and automated interface between imaging and tissue, enabling the development of clinical studies to probe tumor heterogeneity on multiple spatial scales. Understanding this heterogeneity may be key to understand why some tumours respond better to therapy than others.View publication
Publication: Cell Reports Medicine
Petra Mlcochova, Dami Collier, Allyson Ritchie, Sonny M. Assennato, Myra Hosmillo, Neha Goel, Bo Meng, Krishna Chatterjee, Vivien Mendoza, Nigel Temperton, Leo Kiss, Leo C. James, Katarzyna A. Ciazynska, Xiaoli Xiong, John AG. Briggs, James A. Nathan, Federica Mescia, Laura Bergamaschi, Hongyi Zhang, Petros Barmpounakis, Nikos Demeris, Richard Skells, Paul A. Lyons, John Bradley, Steven Baker, Jean Pierre Allain, Kenneth GC. Smith, Rachel Bousfield, Michael Wilson, Dominic Sparkes, Glenn Amoroso, Effrosyni Gkrania-Klotsas, Susie Hardwick, Adrian Boyle, Ian Goodfellow, Ravindra K. Gupta
1 September 2020
Testing patients for COVID-19 as soon as they arrive at hospital is essential to obtain a diagnosis and to make sure they receive the correct treatment as soon as possible.
In a recent Cambridge study, the use of the SAMBA II test reduced the amount of time patients spent on holding wards. Now Cambridge researchers wanted to go further to create a ‘gold-standard’ method of testing.
The most common form of testing is taking a swab of the nose and throat (known as PCR) to see if the virus is present. However, it can take as long as 14 days for an individual to show symptoms of COVID-19, by which time the virus may have moved from the nose and throat and into the lungs and other tissues and organs, making it harder to detect via a swab test. Another way to detect the virus is looking for antibodies (from blood samples) in individuals.
Cambridge researchers combined the two tests – PCR and the antibody test – to help identify who may have the virus. They found combining both tests was more effective to identify patients who had Covid than those who had just one of the tests. Read the full news story.View publication
Publication: Nature Communications
Varun Warrier, David M. Greenberg, Elizabeth Weir Clara Buckingham, Paula Smith, Meng-Chuan Lai, Carrie Allison, Simon Baron-Cohen
7 August 2020
Transgender and gender-diverse individuals are more likely to be autistic and report higher autistic traits
Researchers reviewed over 600,000 people and used five datasets where participants provided information such as gender identity and if they received a diagnosis of autism or other psychiatric conditions such as depression or schizophrenia. Participants also completed a measure of autistic traits.
Researchers found that transgender and gender-diverse adult individuals were between three and six times more likely to indicate that they were diagnosed as autistic compared to cisgender individuals. The study used data from adults who said they had received an autism diagnosis, however, it is likely there are more individuals on the autistic spectrum who are undiagnosed.
This research will help improve access to mental health care and support for transgender and gender-diverse individuals. Read the full news story.View publication
Publication: The Lancet
Prof Rebecca C Fitzgerald, Massimiliano di Pietro, Maria O’Donovan, Roberta Maroni, Beth Muldrew, Irene Debiram-Beecham, Marcel Gehrung, Judith Offman, Monika Tripathi, Samuel G Smith, Benoit Aigret, Fiona M Walter, Prof Greg Rubin, on behalf of theBEST3 Trial team † Prof Peter Sasieni
31 July 2020
Barrett’s oesophagus is a condition that can lead to oesophageal cancer in a small number of people. It’s usually diagnosed in hospital by endoscopy (passing a camera down into the stomach). Samples of cells from any areas that don’t look normal are then collected, but an endoscopy can be uncomfortable and does have some risks.
The Cytosponge test allows the patient to swallow a small capsule with a sponge inside, which is attached to a piece of string. The capsule dissolves after a few minutes, and the sponge inside is released. A nurse then gently pulls the string to remove the sponge. On the way out the sponge collects cells from the lining of the oesophagus. The sample is then taken for analysis using a new laboratory marker called TFF3.
Researchers studied 13,222 participants who were randomly allocated to being offered the sponge test or being looked after by the GP in the usual way. Over the course of a year, the odds of detecting Barrett’s were ten times higher in those who were offered the Cytosponge with 140 cases diagnosed compared to 13 in usual care. In addition, the Cytosponge diagnosed five cases of early cancer (stage 1 and 2), whereas only one case of early cancer was detected in the usual care group.
Alongside better detection, the test means cancer patients can benefit from kinder treatment options if their cancer is caught at a much earlier stage. Read the full news article.
Publication: Cell Reports
Michael C. Lee, Michael S. Nahorski, James R.F. Hockley, Frank Reimann, Ewan St. John Smith, C. Geoffrey Woods
21 July 2020; DOI: 10.1016/j.celrep.2020.107941
Women who don’t need pain relief during childbirth may have a key genetic variant that acts as a natural epidural. Supported by the NIHR Cambridge BRC, researchers investigated why some women experience different levels of pain during childbirth.
Women who did not require any pain relief during the birth of their first child took part in a study to understand their pain threshold. This included applying heat and pressure to their arms and putting their hands in icy water. They were then measured against a control group of women were who were given pain relief during childbirth.
They found the group the women who didn’t need any pain relief had a high pain threshold than those of the control group. Their genetic cold was then sequenced and found these women had a higher-than-expected prevalence of a rare variant of the gene KCNG4. This gene acts as a gate, controlling the electric signal that flows along our nerve cells. This could be the reason why these women did not require pain relief during childbirth. Read the full news articleView publication
Publication: Journal of Neurology, Neurosurgery and Psychiatry
Jonathan Tay, Robin G Morris, Anil M Tuladhar, Masud Husain, Frank-Erik de Leeuw, Hugh S Markus
Cerebral small vessel disease (SVD) is the leading vascular cause of dementia and plays a major role in cognitive decline and mortality.
This research aimed to determine whether apathy or depression predicts all-cause dementia in SVD patients.
Using two prospective cohort studies of SVD, the researchers looked at changes in apathy and depression in 104 patients to predict dementia.
The research indicated that while increasing apathy was associated with dementia, baseline depression and change in depression did not predict dementia.
The researchers concluded that apathy, but not depression, may be an early sign of dementia in SVD, and that this may be useful in identifying at-risk individuals.View publication
Dami A Collier, Sonny M Assennato, Nyarie Sithole, Katherine Sharrocks, Allyson Ritchie, Pooja Ravji, Matt Routledge, Dominic Sparkes, Jordan Skittrall, Ben Warne, Anna Smielewska, Isobel Ramsey, Neha Goel, Martin Curran, David Enoch, Rhys Tassell, Michelle Lineham, Devan Vaghela, Clare Leong, Hoi Ping Mok, John Bradley, Kenneth Gc Smith, Vivien Mendoza, Nikos Demiris, Martin Besser, Gordon Dougan, Paul J Lehner, Hongyi Zhang, Claire Waddington, Helen Lee, Ravindra K Gupta
03 June 2020
SAMBA II machines were deployed in the ED and holding wards at Addenbrooke’s hospital to help detect COVID-19 in patients as part of a research trial called COVIDx.
Researchers investigated whether using the new machines could accurately provide a faster diagnosis than standard testing practices and review how it would affect patient waiting times.
After collecting nose and throat swabs from over 140 patients, the samples were processed using the SAMBA II machine. Researchers found they were able to provide an accurate diagnostic result within 90 minutes, compared to the standard 24-48-hour lab waiting time. Read the full story.View publication
Publication: Journal of Clinical Endocrinology & Metabolism
Katherine Lawler, Isabel Huang-Doran, Takuhiro Sonoyama, Tinh-Hai Collet, Julia M Keogh, Elana Henning, Stephen O’Rahilly, Leonardo Bottolo, I Sadaf Farooqi
11 May 2020
The hormone leptin is a key regulator of weight. Children who lack leptin (due to changes in the leptin gene) have a very large appetite and rapidly gain weight. After treatment with leptin injections, they can lose weight.
The researchers know that leptin works by reducing their appetite, but they wanted to find out if leptin can affect other metabolic processes around the body too.
They used a cutting-edge technique called metabolomics to simultaneously measure more than 600 metabolic reactions in a single blood sample taken from children and young adults before and after a short period of leptin treatment.
They found that leptin not only caused big shifts in how the body processes fats, but it affected amino acids (which make proteins), bile acids (which can act as cell signals) and steroids (involved in making hormones). These changes overlapped with the changes discovered previously in healthy adults after a period of fasting.
The research findings show that as well as affecting how much food we eat, leptin affects other aspects of our metabolism. This research paves the way for further research into leptin’s action on different cells in the human body.View publication
Lucy Rivett, Sushmita Sridhar, Dominic Sparkes, Matthew Routledge, Nick K. Jones, et al
12 May 2020
Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.View publication
James E. D. Thaventhiran, Hana Lango Allen, Kenneth G. C. Smith
06 May 2020
Cambridge researchers sequenced the entire genetic code of 974 people with PID. The team were able to identify variations in genes already known to cause PID. To help identify genetic causes for the remaining participants and other patients with PID, the team used a statistical program known as BeviMed. BeviMed can be used to predict genes that may cause PID, by comparing the genomes of cases and controls. Using this technique, the team were able to identify new genes that cause PID. Full press release hereView publication