Publisher Health

Huddersfield researchers were among the first to demonstrate how the induction of brain inflammation accounts for neurological damage in COVID19 patients and now, their findings have been published in a peer-reviewed medical journal.
The study, published in the journal Molecular Neurobiology led by the University of Huddersfield’s Dr Mayo Olajide, describes how the spike protein used by the coronavirus to enter human cells can have a similar effect on the brain’s immune cells as it does with the rest of the body.
Dr Olajide, who’s previous research discovered how the onset of Alzheimer’s disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate, conducted the potential impact of the Spike Glycoprotein S1 using immune cell lines obtained from mice and is now applying for funding to develop the research further using brain cells from humans.
“Following our hypothesis,” said Dr Olajide, “we are now questioning when the coronavirus has affected the brain, could this pose a risk for neurodegenerative disorders further down the line, like Alzheimer’s or Parkinson’s?”
How the coronavirus activate the brain’s own immune response
According to Dr Olajide, whilst other research demonstrated the mechanism of why the virus was able to gain access into the brain through the nose, theirs was among the first to demonstrate how the coronavirus activated the brain’s own immune response.
“It may not be multiplying in the brain, but when it gets into the brain, it can actually induce immune responses and this explains some of the trends people have reported when they have been infected such as continued brain fog and memory loss,” he said.
Dr Olajide believes if adequate funding can be achieved the research could prove significant.
“The thing with COVID research is so many researchers speculate but less actually carry out the experiments needed to prove their research because it takes such a long time to complete.”
Dr Olajide is a Reader within the University’s Department of Pharmacy in the School of Applied Sciences. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.
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Materials provided by University of Huddersfield. Note: Content may be edited for style and length.

A potential cornucopia of neuroactive compounds, which might yield clues to the design of future psychiatric and neurological drugs, has become more accessible to synthetic chemists, thanks to new work from Scripps Research.
The discovery, reported March 17, 2022, in Science, concerns compounds contained in the rainforest tree Galbulimima belgraveana and its close cousin Galbulimima baccata, which are native to Papua New Guinea, tropical northern Australia, and Malaysia.
Potions made from the bark of these trees have long been known to have hallucinogenic and other neuroactive effects, but the precise compounds involved, and their biological targets, have largely been a mystery. The Scripps Research chemists found what is essentially the first streamlined, practical method for synthesizing many of these compounds.
“We’re very interested in learning how these Galbulimima compounds affect the brain, and hope to derive useful new therapeutics from them. Now with this improved approach to making these molecules, we can start to do just that,” says Ryan Shenvi, PhD, the professor of chemistry at Scripps Research who led the study.
The co-first authors of the study were Eleanor Landwehr, Meghan Baker PhD, and Takuya Oguma PhD, who worked in the Shenvi lab during the study.
The neuroactive effects of compounds found in Galbulimima bark were first highlighted just after World War II in surveys by the pharma company Smith, Kline & French and the Australian national research organization CSIRO. Until now, though, the dense structural complexity of these compounds, their variable mix within Galbulimima bark, and the difficulty of obtaining that bark in quantity, have prevented their close study. Indeed, chemists had devised a concise and practical synthesis for only one of these compounds, himbacine.
In the new study, Shenvi and his team targeted another Galbulimima compound called himgaline, which, like himbacine, appears to have antispasmodic properties, though it is likely to act in a different way. Whereas the best prior method to synthesize himgaline requires 19 steps — too many for routine use — the new method took only 7 steps, enabling easy synthesis at the scale needed to study the compound in detail.
Shenvi says the new method is more efficient in part because it starts with a broad approach to the chemical “space” or “neighborhood” around himgaline, allowing that specific compound — or other related compounds — to be made relatively easily from there. Using this approach, the team demonstrated syntheses of himgaline and two other Galbulimima compounds, GB22 and GB13.
“Our approach is somewhat analogous to distant space travel — we first try to get to the target star system, so to speak, and from there it’s relatively easy to get to specific planets within that system,” Shenvi says.
Shenvi and his team are now following up with studies of the biological properties of himgaline, GB22 and GB13, and are also using their broad synthesis strategy to make and study other Galbulimima compounds.
“Concise syntheses of GB22, GB13, and himgaline by cross-coupling and complete reduction” was co-authored by Eleanor Landwehr, Meghan Baker, Takuya Oguma, Hannah Burdge, Takahiro Kawajiri and Ryan Shenvi, who were all at Scripps Research during the study.
The work was funded in part by the National Institutes of Health (GM122606) and the National Science Foundation (CHE1856747).

Leicester researchers have described application of a pioneering chemical technique which could unlock ground-breaking new treatments for cancer and other diseases.
Members of the Leicester Institute of Structural and Chemical Biology, based at the University of Leicester, used proteolysis targeting chimeras (PROTACs) as a ‘bridge’ to degrade proteins implicated in cancer.
Scientists can manipulate the effectiveness of treatments by making changes to elements of this PROTAC bridge.
This new study, published in the Journal of Medicinal Chemistry, describes how Leicester researchers applied a previously-described protein degradation technique known as PROTACs to degrade histone deacetylation enzymes (HDACs) in a more targeted way than ever before.
HDACs play an important role in gene regulation, in which genes are switched ‘on’ and ‘off’, and are associated with a range of diseases, including cancer as well as various neurodegenerative disorders including Alzheimer’s disease.
Using this pioneering technique to target specific structures within cancerous cells could increase the potency and selectivity of new and existing drugs, meaning patients would require lower systemic exposure to drug treatments leading to a reduction in harmful side-effects to patients.

The light we experience across our daily lives has a major influence on our body rhythms. Modern lifestyles, with 24-hour access to electric light and reduced exposure to natural daylight, can disrupt sleep and negatively impact health, well-being, and productivity. A new report publishing March 17 in the open access journal PLOS Biology addresses the issue of exactly how bright lighting should be during the day and in the evening to support healthy body rhythms, restful sleep, and daytime alertness.
Professors Timothy Brown from the University of Manchester, UK, and Kenneth Wright from the University of Colorado Boulder, US brought together an international body of leading scientific experts to agree the first evidence-based, consensus recommendations for healthy daytime, evening, and nighttime light exposure. These recommendations provide much needed guidance to the lighting and electronics industries to aid the design of healthier environments and to improve how we light our workplaces, public buildings, and homes.
A key question tackled by the new report was how to properly measure the extent to which different types of lighting might influence our body rhythms and daily patterns of sleep and wakefulness. Light affects these patterns via a specialized type of cell in the eye that uses a light sensitive protein, melanopsin, that is distinct from the proteins in the rods and cones that support vision (and upon which traditional ways of measuring “brightness” are based). Since melanopsin is most sensitive to light in a specific part of the visual spectrum (blue-cyan light), the new recommendations used a newly-developed light measurement standard tailored to this unique property, melanopic equivalent daylight illuminance. Analysis of data across a range of laboratory and field studies proved that this new measurement approach could provide a reliable way of predicting the effects of light on human physiology and body rhythms and could therefore form the basis of widely applicable and meaningful recommendations.
An important next step will be integration of the recommendations into formal lighting guidelines, which currently focus on visual requirements rather than effects on health and well-being. Additionally, increasing sophistication in LED lighting technology and the availability of low-cost light sensors are expected to increase the ease with which individuals can optimize their personal light exposure to best support their own body rhythms in line with the new recommendations.
Brown adds, “These recommendations provide the first scientific consensus, quantitative, guidance for appropriate daily patterns of light exposure to support healthy body rhythms, nighttime sleep and daytime alertness. This now provides a clear framework to inform how we light any interior space ranging from workplaces, educational establishments and healthcare facilities to our own homes.”
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Materials provided by PLOS. Note: Content may be edited for style and length.

Researchers have identified a link suggesting that lithium could decrease the risk of developing dementia, which affects nearly one million people in the UK.
The researchers, from the University of Cambridge, conducted a retrospective analysis of the health records of nearly 30,000 patients from Cambridgeshire and Peterborough NHS Foundation Trust. The patients were all over the age of 50 and accessed NHS mental health services between 2005 and 2019.
The analysis suggested that patients who received lithium were less likely to develop dementia than those who did not, although the overall number of patients who received lithium was small.
Their findings, reported in the journal PLoS Medicine, support the possibility that lithium could be a preventative treatment for dementia, and could be progressed to large randomised controlled trials.
Dementia is the leading cause of death in elderly Western populations, but no preventative treatments are currently available: more than 55 million people worldwide have dementia, with Alzheimer’s disease the most common form.
“The number of people with dementia continues to grow, which puts huge pressure on healthcare systems,” said Dr Shanquan Chen from Cambridge’s Department of Psychiatry, the paper’s first author. “It’s been estimated that delaying the onset of dementia by just five years could reduce its prevalence and economic impact by as much as 40 percent.”
Previous studies have proposed lithium as a potential treatment for those who have already been diagnosed with dementia or early cognitive impairment, but it is unclear whether it can delay or even prevent the development of dementia altogether, as these studies have been limited in size.

Scientists have long known that learning requires the flow of calcium into and out of brain cells. But researchers at Columbia’s Zuckerman Institute have now discovered that floods of calcium originating from within neurons can also boost learning. The finding emerged from studies of how mice remember new places they explore.
Published today in Science, the new research doesn’t suggest that you should drink more calcium-rich milk to pass that math class. It provides a better understanding of the mechanisms that underlie learning and memory: knowledge that could help shed light on disorders such as Alzheimer’s disease.
“The cells we studied in this new work are in the hippocampus, the first area of the brain affected by Alzheimer’s disease,” said Franck Polleux, PhD, a principal investigator at Columbia’s Zuckerman Institute. “Understanding the basic principles of what allows these brain cells to encode memory will provide tremendous insights into what goes wrong in this disease.”
The brain’s ability to learn and remember — everything from our first words and steps to where we parked our car or left our keys — depends on the gaps where neurons connect to each other, called synapses. Synapses, through which cells exchange information, can be modified over time. This malleability to experience, known as plasticity, relies on how calcium ions flow within the brain.
Nearly all research into the part that calcium plays in plasticity has focused on how it can rush into and out of a synapse through channels on the surfaces of neurons. For more than two decades, scientists have suspected that stockpiles of calcium within neurons might also play a major role in shaping plasticity. But until now, scientists had no way to investigate the effects that calcium discharged from these internal reservoirs had within the mammalian brain.
“For a long time, there were no good tools out there to really probe this intracellular calcium release in a living animal as it learned,” said postdoctoral researcher and first author Justin O’Hare, PhD, in the Polleux lab and the lab of Attila Losonczy, MD, PhD, at Columbia’s Zuckerman Institute.

One of the most common disorders globally, nonalcoholic fatty liver disease (NAFLD) is a leading cause of death worldwide. Its progressive form, called “nonalcoholic steatohepatitis” (NASH), affects about 30% of all NAFLD patients, and can lead to cirrhosis and liver cancer. Despite many research efforts, we still do not understand the underlying mechanisms of NAFLD/NASH and, consequently, lack an effective treatment.
One thing we do know, however, is that it seems to be more frequent among men than women, especially premenopausal women. Why this is so is not entirely clear, but current evidence suggests that the sex hormone estrogen plays a protective role. On the other hand, the protein formyl peptide receptor 2 (FPR2) is known to play an important role in mediating inflammatory responses in multiple organs. However, no study so far has determined its role in the liver. Could FPR2 be involved in the sex-related differences regarding NAFLD prevalence and severity?
Addressing this question, a research team led by Professor Youngmi Jung of Pusan National University, Korea, recently conducted a study using mice model, shedding light on the role of FPR2 in NAFLD/NASH and its relationship to the observed sex-based differences. This work is among the very few studies on NAFLD that relies on sex-balanced animal experiments rather than the more common male-only designs. This paper was made available online on 31 January 2022 and was published in Volume 13, Issue 578, of the journal Nature Communications on 31 January 2022.
The researchers first found that Fpr2 was highly expressed in healthy livers of female mice. Furthermore, it was expressed differently in the livers of male and female mice that were fed a special NAFLD-inducing diet. Silencing the Fpr2 gene made the male and female mice equally vulnerable to NAFLD, suggesting that FPR2 has a protective effect on the liver.
Interestingly, the researchers also found that FPR2 production in the liver is mediated by estrogen. Males supplemented with external estrogen produced more Fpr2 and were more resistant to NAFLD, whereas females that had their ovaries removed exhibited reduced liver Fpr2 levels. “Taken together, our findings suggest that FPR2 is a potential therapeutic target for developing pharmacological agents to treat NAFLD/NASH,” says Prof. Jung. “In addition, our results could help in the development of gender-based therapies for NASH.”
This unprecedented discovery of the female-specific production of FPR2 in the liver and its role in providing resistance against NAFLD/NASH will hopefully pave the way not only for novel treatments but also a more comprehensive and sex-aware approach when doing science. In this regard, Prof. Jung remarks, “Our research highlights the pressing need for designing and developing better sex-balanced animal experiments, considering that the sex-specific expression of FPR2 in the liver had been completely overlooked in previous studies.”
Let us hope this marks the beginning of a deeper understanding of NAFLD/NASH and the first steps towards effective sex-based therapies.
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Materials provided by Pusan National University. Original written by Na-hyun Lee. Note: Content may be edited for style and length.

An artificial intelligence (AI) tool can accurately and consistently classify breast density on mammograms, according to a study in Radiology: Artificial Intelligence.
Breast density reflects the amount of fibroglandular tissue in the breast commonly seen on mammograms. High breast density is an independent breast cancer risk factor, and its masking effect of underlying lesions reduces the sensitivity of mammography. Consequently, many U.S. states have laws requiring that women with dense breasts be notified after a mammogram, so that they can choose to undergo supplementary tests to improve cancer detection.
In clinical practice, breast density is visually assessed on two-view mammograms, most commonly with the American College of Radiology Breast Imaging-Reporting and Data System (BI-RADS) four-category scale, ranging from Category A for almost entirely fatty breasts to Category D for extremely dense. The system has limitations, as visual classification is prone to inter-observer variability, or the differences in assessments between two or more people, and intra-observer variability, or the differences that appear in repeated assessments by the same person.
To overcome this variability, researchers in Italy developed software for breast density classification based on a sophisticated type of AI called deep learning with convolutional neural networks, a sophisticated type of AI that is capable of discerning subtle patterns in images beyond the capabilities of the human eye. The researchers trained the software, known as TRACE4BDensity, under the supervision of seven experienced radiologists who independently visually assessed 760 mammographic images.
External validation of the tool was performed by the three radiologists closest to the consensus on a dataset of 384 mammographic images obtained from a different center.
TRACE4BDensity showed 89% accuracy in distinguishing between low density (BI-RADS categories A and B) and high density (BI-RADS categories C and D) breast tissue, with an agreement of 90% between the tool and the three readers. All disagreements were in adjacent BI-RADS categories.
“The particular value of this tool is the possibility to overcome the suboptimal reproducibility of visual human density classification that limits its practical usability,” said study co-author Sergio Papa, M.D., from the Centro Diagnostico Italiano in Milan, Italy. “To have a robust tool that proposes the density assignment in a standardized fashion may help a lot in decision-making.”
Such a tool would be particularly valuable, the researchers said, as breast cancer screening becomes more personalized, with density assessment accounting for one important factor in risk stratification.
“A tool such as TRACE4BDensity can help us advise women with dense breasts to have, after a negative mammogram, supplemental screening with ultrasound, MRI or contrast-enhanced mammography,” said study co-author Francesco Sardanelli, M.D., from the IRCCS Policlinico San Donato in San Donato, Italy.
The researchers plan additional studies to better understand the full capabilities of the software.
“We would like to further assess the AI tool TRACE4BDensity, particularly in countries where regulations on women density is not active, by evaluating the usefulness of such tool for radiologists and patients,” said study co-author Christian Salvatore, Ph.D., senior researcher, University School for Advanced Studies IUSS Pavia and co-founder and chief executive officer of DeepTrace Technologies.
“Development and Validation of an AI-driven Mammographic Breast Density Classification Tool Based on Radiologist Consensus.” Collaborating with Drs. Papa, Sardanelli and Salvatore were Veronica Magni, M.D., Matteo Interlenghi, M.Sc., Andrea Cozzi, M.D., Marco Alì, Ph.D., Alcide A. Azzena, M.D., Davide Capra, M.D., Serena Carriero, M.D., Gianmarco Della Pepa, M.D., Deborah Fazzini, M.D., Giuseppe Granata, M.D., Caterina B. Monti, M.D., Ph.D., Giulia Muscogiuri, M.D., Giuseppe Pellegrino, M.D., Simone Schiaffino, M.D., and Isabella Castiglioni, M.Sc., M.B.A.

Metastases in cancer are often caused by a few abnormal cells. These behave more aggressively than the other cancer cells in a tumour. Miao-Ping Chien and Daan Brinks are working together, from two different universities, on a method to detect these cells. Their research has now been published in Nature.
A patient diagnosed with cancer has increasingly better prospects nowadays, because the medicines are becoming more effective. However, one risk remains. Even after the tumour has shrunk, it can start growing again after a while and spread to other organs. This aggressive spread through the body is usually caused by a small group of cells. “These cancer stem cells behave differently from other cells and therefore have a significant impact on cancer recurrence,” says Miao-Ping Chien of Erasmus MC, who works closely with Daan Brinks of TU Delft. Their collaboration is a cross-pollination between two multidisciplinary labs located just fifteen kilometres apart. Brinks: “It’s easy to just jump on the bike or in the car to get to the other lab to do a few more tests at the end of the day.” What is special about their story is that they are not just colleagues but also partners. The couple came to the Netherlands together to join forces in cancer research.
Detecting a few cells that behave differently in a tumour has been a major challenge in the field of cancer research for many years. Chien: “We’ve known that they’re there for a long time, but the Holy Grail is to be able to sequence precisely those cells, to find out their DNA and RNA content. Merely examining the outside of the cell is not enough for these special cells. Although certain characteristic substances can be found there, the so-called biomarkers, these are quite changeable in such an aggressive cell.” To know how those cells really work, Chien and Brinks need to decipher the genetic sequence. This makes it easier to determine how these cells work and also how they can be destroyed. Determining the genetic profile of cells has been possible for some time now, but determining the profile of individual cells has only been possible since a few years.
Deviant behaviour
Chien and Brinks had to combine a whole range of techniques to be sure they had got the right cells. By working with two labs to piece together and fine-tune a complicated process, it is now possible to detect aggressive cancer cells, light them up, separate them from the other cells and then determine the RNA sequence. “The first question was: how do these aggressive cells behave? For example, we know that they move around more than other cells. And that they don’t split up into two cells, as in normal cell division, but into three or four cells,” explains Chien. So she had to look for such cells in a biopsy specimen, that is, a piece of cancer tissue.
Imaging, lighting up and analysing
The two researchers needed a microscope that could image a very large number of cells simultaneously as well as software to analyse the images. Together with the people working in their labs, they developed a microscope that continuously studies the images and ‘sees’ which cells are exhibiting abnormal behaviour. This behaviour of aggressive cancer cells unfolds within a time scale of minutes to hours, but analysing this behaviour needs to be done much faster. “After all, you don’t want the detected cells to have already moved again,” Brinks explains. The microscope directs a light beam onto the detected aggressive cancer cells. The cells light up because the tissue has been treated with a special substance in advance. Next, the lit-up cells are selected and these are now ready for RNA sequencing and analysis. They only need a few to a few hundred cells.
Medicines
“We can now determine the genetic profile of the aggressive cancer cells. This was not so easy to do at first, because you have to deal with all the challenges of imaging, selecting and determining the RNA sequence in one go. Everything in the process has to work properly,” says Chien. “And if you know what’s going on in those cells, you can develop medicines based on that. We’ve succeeded in discovering a mechanism within a few months, whereas others needed quite a few years with the existing techniques. We just happened to come out with it at about the same time. Maybe, with our method, it can eventually be done within a few weeks.” The two are now setting up a company called UFO Biosciences, so that researchers from all over the world can send in cell samples or pieces of cancer tissue for analysis. According to them, there is already a great deal of interest from other universities and research institutes.
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Materials provided by Delft University of Technology. Note: Content may be edited for style and length.

A study published in the journal Nature Cancer, carried out within the Cancer Programme at the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar) by the Cancer Stem Cells and Metastasis Dynamics Laboratory, led by Dr. Toni Celià-Terrassa, and the Laboratory of Molecular Cancer Therapy, coordinated by Dr. Joan Albanell, with the participation of international centres, has discovered an approach that radically increases the success of immunotherapy in one of the most aggressive types of tumours, triple-negative breast cancer. This subtype, although accounting for only 15% of cases, is one of the most rapidly progressing and affects younger patients. In this work, researchers found that tumour stem cells are the main cause of immunotherapy resistance in this subtype of breast cancer. The reason is that these cells are invisible to the immune system, making immunotherapy ineffective. In addition, the study offers a promising solution to this situation by using a new therapeutic approach in preclinical models that makes cancer stem cells visible to the immune system so that it can then eliminate the tumour.
This subpopulation of more aggressive cells may represent between 5% and 50% of the entire tumour population in triple-negative breast cancer. They have low levels of LCOR factor, which plays a key but previously unknown role in allowing cells to present antigens on their surface, molecules that enable the immune system to differentiate normal cells from tumour cells and attack the latter. Consequently, in the case of tumour stem cells, the low presence of this LCOR factor makes them invisible to the body’s defences. As a result, these cells are resistant to breast cancer immunotherapy, which has a relatively low success rate in current clinical practice.
A mechanism that provokes treatment resistance
This ability of tumour stem cells to remain invisible to the immune system allows them to withstand immunotherapy treatment. As Dr. Toni Celià-Terrassa explains, “We have seen how, despite immunotherapy treatment, these cells survive and have the ability to generate resistance, which is linked to their ability to hide from the immune system, allowing them to evade immunotherapy.”
Using mouse models, the researchers have demonstrated how this situation is reversed when the LCOR gene is activated in this type of cell, setting in motion the machinery that allows the immune system to detect the tumour. “It involves reconfiguring the tumour to make it completely visible and, therefore, sensitive to immunotherapy, transforming it from invisible to visible,” says Iván Pérez-Núñez, a pre-doctoral researcher in the Cancer Stem Cells and Metastasis Dynamics Laboratory and first author of the study. The researchers were able to see how, by combining this approach with immunotherapy, the treatment response rate was total, and all tumours were eliminated, curing the mice in the long term. This prevents both the recurrence of cancer and the generation of resistance.
Pioneering study on the use of messenger-RNA therapy in cancer and immunotherapy
Inspired by the technology used in the design of messenger-RNA vaccines for COVID-19, the researchers decided to use a similar strategy to transport and deliver LCOR gene RNA into tumour cells and trigger its function. Biological nanovesicles, small bag-like structures formed in the cells, were developed to carry this information and were shown to do so successfully, preventing the tumour stem cells from remaining invisible.
“What we are doing is making the immune system see the tumour cell better. Unlike healthy cells, malignant cells have a much higher load of recognised ‘foreign’ antigens, which are not inherent to the immune system. In this way, the body’s natural defences will recognise, attack and eliminate the malignant cells,” explains Dr. Celià-Terrassa. In this sense, he points out that “We have discovered how to make this type of breast cancer respond to immunotherapy in preclinical models, making these cells visible thanks to the use of the antigen-presenting mechanism, thereby boosting the immunotherapy response and its efficiency.”
This strategy may be applicable to other types of breast cancer tumours and other tumour types, although safety studies and clinical trials in humans are needed first. Even so, according to Dr. Joan Albanell, co-leader of the study, director of the Cancer Research Programme at IMIM-Hospital del Mar and head of the Oncology Department at Hospital del Mar, this approach does open up new possibilities. “What is important is that the experimental results demonstrate an unprecedented sensitisation of triple-negative breast cancer to immunotherapy, making resistant tumours virtually curable,” says Dr Albanell, also a professor at the UPF. “This unequivocally motivates us to investigate therapeutic strategies that may culminate in clinical trials, and to explore whether it could be applicable to other tumours,” he concludes.
The use of LCOR in combination with immunotherapy has generated a patent and a spin-off company will be created to develop this. “The project led by Dr. Celià-Terrassa and Dr. Albanell is a paradigmatic example of research in immune therapies that will be boosted in the near future by the new Immuno-oncology Division that we are creating at the IMIM,” explains Dr. Joaquín Arribas, director of the IMIM-Hospital del Mar and author of the study.
The study was made possible thanks to a CLIP grant from the US Cancer Research Institute and funding from the Carlos III Health Institute (ISCIII). Thanks also go to the Spanish Association Against Cancer (Asociación Española contra el Cáncer; AECC), the Fero Foundation and CIBERONC, a centre to which the two researchers who led the study also belong.