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The group of bacteria called Enterobacteriaceae, including Klebsiella pneumoniae, Shigella, E.coli and others, is present at low levels as part of a healthy human gut microbiome. But at high levels - caused for example by increased inflammation in the body, or by eating contaminated food - these bugs can cause illness and disease. In extreme cases, too much Enterobacteriaceae in the gut can be life-threatening.

Researchers have used computational approaches including AI to analyse the gut microbiome composition of over 12,000 people across 45 countries from their stool samples. They found that a person’s microbiome ‘signature’ can predict whether a person’s gut is likely to be colonised by Enterobacteriaceae. The results are consistent across different states of health and geographic locations.

The researchers identified 135 gut microbe species that are commonly found in the absence of Enterobacteriaceae, likely protecting against infection.

Notable amongst the protective gut species are a group of bacteria called Faecalibacterium, which produce beneficial compounds called short-chain fatty acids by breaking down fibre in the foods we eat. This seems to protect against infection by a range of disease-causing Enterobacteriaceae bugs.

The researchers suggest that eating more fibre in our diet will support the growth of good bacteria - and crowd out the bad ones to significantly reduce the risk of illness.

In contrast, taking probiotics - which don’t directly change the environment in the gut - is less likely to affect the likelihood of Enterobacteriaceae infection.

The results are published today in the journal Nature Microbiology. 

“Our results suggest that what we eat is potentially very important in controlling the likelihood of infection with a range of bacteria, including E.coli and Klebsiella pneumoniae, because this changes our gut environment to make it more hostile to invaders,” said Dr Alexandre Almeida, a researcher at the University of Cambridge’s Department of Veterinary Medicine and senior author of the paper.

He added: “By eating fibre in foods like vegetables, beans and whole grains, we can provide the raw material for our gut bacteria to produce short chain fatty acids - compounds that can protect us from these pathogenic bugs.”

Klebsiella pneumonia can cause pneumonia, meningitis and other infections. The alarming global rise in antibiotic resistance to this bacterial pathogen has led scientists to look for new ways of keeping it, and other similar infectious bacteria, under control. 

“With higher rates of antibiotic resistance there are fewer treatment options available to us. The best approach now is to prevent infections occurring in the first place, and we can do this by reducing the opportunities for these disease-causing bacteria to thrive in our gut,” said Almeida.

A new understanding of gut microbe interactions

Earlier research to understand interactions between the different bacteria in our gut has used mouse models. But some of these new results are at odds with previous findings. 

The new study revealed that 172 species of gut microbe can coexist with disease-causing Enterobacteriaceae bugs. Many of these species are functionally similar to the bugs: they need the same nutrients to survive. Previously it was thought that competition for resources would stop the disease-causing bacteria from getting established in the gut.

This has important implications for treatment: taking probiotics that compete for the same nutrients with the bad bacteria to try and starve them out isn’t going to work. The researchers say that it will be more beneficial to change the environment in the gut, for instance through diet, to reduce the risk of infection with Enterobacteriaceae.

“This study highlights the importance of studying pathogens not as isolated entities, but in the context of their surrounding gut microbiome,” said Dr Qi Yin, a visiting researcher at the University of Cambridge’s Department of Veterinary Medicine and first author of the report.

The research was funded by the Medical Research Council.

Reference: Yin, Q. et al: 'Ecological dynamics of Enterobacteriaceae in the human gut microbiome across global populations.’ Jan 2025, Nature Microbiology. DOI: 10.1038/s41564-024-01912-6.

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A new study has found that the composition of your gut microbiome helps predict how likely you are to succumb to potentially life-threatening infection with Klebsiella pneumoniae, E.coli and other bugs - and it may be altered by changing your diet.

Our results suggest that what we eat is potentially very important in controlling the likelihood of infection with a range of bacteria.Alexandre AlmeidaCredit Oleksandra Troian GettyIntestine with microbiome

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The new approach uses samples from infected humans to allow real-time monitoring of pathogens circulating in human populations, and enable vaccine-evading bugs to be quickly and automatically identified. This could inform the development of vaccines that are more effective in preventing disease.

The approach can also quickly detect emerging variants with resistance to antibiotics. This could inform the choice of treatment for people who become infected - and try to limit the spread of the disease.

It uses genetic sequencing data to provide information on the genetic changes underlying the emergence of new variants. This is important to help understand why different variants spread differently in human populations.

There are very few systems in place to keep watch for emerging variants of infectious diseases, apart from the established COVID and influenza surveillance programmes. The technique is a major advance on the existing approach to these diseases, which has relied on groups of experts to decide when a circulating bacteria or virus has changed enough to be designated a new variant.

By creating ‘family trees’, the new approach identifies new variants automatically based on how much a pathogen has changed genetically, and how easily it spreads in the human population – removing the need to convene experts to do this. 

It can be used for a broad range of viruses and bacteria and only a small number of samples, taken from infected people, are needed to reveal the variants circulating in a population. This makes it particularly valuable for resource-poor settings.

The report is published today in the journal Nature.

“Our new method provides a way to show, surprisingly quickly, whether there are new transmissible variants of pathogens circulating in populations - and it can be used for a huge range of bacteria and viruses,” said Dr Noémie Lefrancq, first author of the report, who carried out the work at the University of Cambridge’s Department of Genetics.

Lefrancq, who is now based at ETH Zurich, added: “We can even use it to start predicting how new variants are going to take over, which means decisions can quickly be made about how to respond.” 

“Our method provides a completely objective way of spotting new strains of disease-causing bugs, by analysing their genetics and how they’re spreading in the population. This means we can rapidly and effectively spot the emergence of new highly transmissible strains,” said Professor Julian Parkhill, a researcher in the University of Cambridge’s Department of Veterinary Medicine who was involved in the study.

Testing the technique

The researchers used their new technique to analyse samples of Bordetella pertussis, the bacteria that causes whooping cough. Many countries are currently experiencing their worst whooping cough outbreaks of the last 25 years. It immediately identified three new variants circulating in the population that had been previously undetected.

“The novel method proves very timely for the agent of whooping cough, which warrants reinforced surveillance given its current comeback in many countries and the worrying emergence of antimicrobial resistant lineages,” said Professor Sylvain Brisse, Head of the National Reference Center for whooping cough at Institut Pasteur, who provided bioresources and expertise on Bordetella pertussis genomic analyses and epidemiology.

In a second test, they analysed samples of Mycobacterium tuberculosis, the bacteria that causes Tuberculosis. It showed that two variants with resistance to antibiotics are spreading.

“The approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible,” said Professor Henrik Salje in the University of Cambridge’s Department of Genetics, senior author of the report.

He added: “If we see a rapid expansion of an antibiotic-resistant variant, then we could change the antibiotic that’s being prescribed to people infected by it, to try and limit the spread of that variant.”

The researchers say this work is an important piece in the larger jigsaw of any public health response to infectious disease.

A constant threat

Bacteria and viruses that cause disease are constantly evolving to be better and faster at spreading between us. During the COVID pandemic, this led to the emergence of new strains: the original Wuhan strain spread rapidly but was later overtaken by other variants, including Omicron, which evolved from the original and were better at spreading. Underlying this evolution are changes in the genetic make-up of the pathogens.

Pathogens evolve through genetic changes that make them better at spreading. Scientists are particularly worried about genetic changes that allow pathogens to evade our immune system and cause disease despite us being vaccinated against them. 

“This work has the potential to become an integral part of infectious disease surveillance systems around the world, and the insights it provides could completely change the way governments respond,” said Salje.

The research was primarily funded by the European Research Council.

Reference: Lefrancq, N. et al: ‘Learning the fitness dynamics of pathogens from phylogenies.’ January 2025, DOI: 10.1038/s41586-024-08309-9
 

Researchers have come up with a new way to identify more infectious variants of viruses or bacteria that start spreading in humans - including those causing flu, COVID, whooping cough and tuberculosis.

The approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible.Henrik SaljeMilan Krasula on Getty

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Desert locusts typically lead solitary lives until something - like intense rainfall - triggers them to swarm in vast numbers, often with devastating consequences. 

This migratory pest can reach plague proportions, and a swarm covering one square kilometre can consume enough food in one day to feed 35,000 people. Such extensive crop destruction pushes up local food prices and can lead to riots and mass starvation.

Now a team led by the University of Cambridge has developed a way to predict when and where desert locusts will swarm, so they can be dealt with before the problem gets out of hand. 

It uses weather forecast data from the UK Met Office, and state-of the-art computational models of the insects’ movements in the air, to predict where swarms will go as they search for new feeding and breeding grounds. The areas likely to be affected can then be sprayed with pesticides.

Until now, predicting and controlling locust swarms has been ‘hit and miss’, according to the researchers. Their new model, published today in the journal PLOS Computational Biology, will enable national agencies to respond quickly to a developing locust threat.

Desert locust control is a top priority for food security: it is the biggest migratory pest for smallholder farmers in many regions of Africa and Asia, and capable of long-distance travel across national boundaries.

Climate change is expected to drive more frequent desert locust swarms, by causing trigger events like cyclones and intense rainfall. These bring moisture to desert regions that allows plants to thrive, providing food for locusts that triggers their breeding.

“During a desert locust outbreak we can now predict where swarms will go several days in advance, so we can control them at particular sites. And if they’re not controlled at those sites, we can predict where they’ll go next so preparations can be made there,” said Dr Renata Retkute, a researcher in the University of Cambridge’s Department of Plant Sciences and first author of the paper.

“The important thing is to respond quickly if there’s likely to be a big locust upsurge, before it causes a major crop loss.  Huge swarms can lead to really desperate situations where people could starve,” said Professor Chris Gilligan in the University of Cambridge’s Department of Plant Sciences, senior author of the paper.

He added: “Our model will allow us to hit the ground running in future, rather than starting from scratch as has historically been the case.”

The team noticed the need for a comprehensive model of desert locust behaviour during the response to a massive upsurge over 2019-2021, which extended from Kenya to India and put huge strain on wheat production in these regions. The infestations destroyed sugarcane, sorghum, maize and root crops. The researchers say the scientific response was hampered by the need to gather and integrate information from a range of disparate sources.

“The response to the last locust upsurge was very ad-hoc, and less efficient than it could have been. We’ve created a comprehensive model that can be used next time to control this devastating pest,” said Retkute. 

Although models like this have been attempted before, this is the first that can rapidly and reliably predict swarm behaviour. It takes into account the insects’ lifecycle and their selection of breeding sites, and can forecast locust swarm movements both short and long-term. 

The new model has been rigorously tested using real surveillance and weather data from the last major locust upsurge. It will inform surveillance, early warning, and management of desert locust swarms by national governments, and international organisations like the Food and Agriculture Organisation of the United Nations (FAO).

The researchers say countries that haven’t experienced a locust upsurge in many years are often ill-prepared to respond, lacking the necessary surveillance teams, aircraft and pesticides. As climate change alters the movement and spread of major swarms, better planning is needed - making the new model a timely development.

The project involved collaborators at the FAO and the UK Met Office. It was funded by the UK Foreign, Commonwealth and Development Office and the Bill and Melinda Gates Foundation.

Reference: Retkute, R., et al: ‘A framework for modelling desert locust population dynamics and large-scale dispersal.’ PLOS Computational Biology, December 2024. DOI: 10.1371/journal.pcbi.1012562
 

A new tool that predicts the behaviour of desert locust populations will help national agencies to manage huge swarms before they devastate food crops in Africa and Asia. 

The response to the last locust upsurge was very ad-hoc, and less efficient than it could have been. We’ve created a comprehensive model that can be used next time to control this devastating pest.Renata RetkuteKeith Cressman, FAOLocust swarm fills the skies in Ethiopia

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The technique, called hyperpolarised carbon-13 imaging, can increase the detected signal in an MRI scanner by more than 10,000 times. Scientists have found that the technique can distinguish between 2 different subtypes of ovarian cancer, to reveal their sensitivities to treatment.

They used it to look at patient-derived cell models that closely mimic the behaviour of human high grade serous ovarian cancer, the most common lethal form of the disease. The technique clearly shows whether a tumour is sensitive or resistant to Carboplatin, one of the standard first-line chemotherapy treatments for ovarian cancer. 

This will enable oncologists to predict how well a patient will respond to treatment, and to see how well the treatment is working within the first 48 hours. 

Different forms of ovarian cancer respond differently to drug treatments. With current tests, patients typically wait for weeks or months to find out whether their cancer is responding to treatment. The rapid feedback provided by this new technique will help oncologists to adjust and personalise treatment for each patient within days.

The study compared the hyperpolarised imaging technique with results from Positron Emission Tomography (PET) scans, which are already widely used in clinical practice. The results shows that PET did not pick up the metabolic differences between different tumour subtypes, so could not predict the type of tumour present.

The report is published today in the journal Oncogene.

“This technique tells us how aggressive an ovarian cancer tumour is, and could allow doctors to assess multiple tumours in a patient to give a more holistic assessment of disease prognosis so the most appropriate treatment can be selected,” said Professor Kevin Brindle in the University of Cambridge’s Department of Biochemistry, senior author of the report. 

Ovarian cancer patients often have multiple tumours spread throughout their abdomen. It isn’t possible to take biopsies of all of them, and they may be of different subtypes that respond differently to treatment. MRI is non-invasive, and the hyperpolarised imaging technique will allow oncologists to look at all the tumours at once.

Brindle added: “We can image a tumour pre-treatment to predict how likely it is to respond, and then we can image again immediately after treatment to confirm whether it has indeed responded. This will help doctors to select the most appropriate treatment for each patient and adjust this as necessary. 

“One of the questions cancer patients ask most often is whether their treatment is working. If doctors can speed their patients onto the best treatment, then it’s clearly of benefit.”

The next step is to trial the technique in ovarian cancer patients, which the scientists anticipate within the next few years.

Hyperpolarised carbon-13 imaging uses an injectable solution containing a ‘labelled’ form of the naturally occurring molecule pyruvate. The pyruvate enters the cells of the body, and the scan shows the rate at which it is broken down - or metabolised – into a molecule called lactate. The rate of this metabolism reveals the tumour subtype and thus its sensitivity to treatment.

This study adds to the evidence for the value of the hyperpolarised carbon-13 imaging technique for wider clinical use. 

Brindle, who also works at the Cancer Research UK Cambridge Institute, has been developing this imaging technique to investigate different cancers for the last two decades, including breast, prostate and glioblastoma - a common and aggressive type of brain tumour. Glioblastoma also shows different subtypes that vary in their metabolism, which can be imaged to predict their response to treatment. The first clinical study in Cambridge, which was published in 2020, was in breast cancer patients.

Each year about 7,500 women in the UK are diagnosed with ovarian cancer - around 5,000 of these will have the most aggressive form of the disease, called high-grade serous ovarian cancer (HGSOC). 

The cure rate for all forms of ovarian cancer is very low and currently only 43% of women in England survive five years beyond diagnosis. Symptoms can easily be missed, allowing the disease to spread before a woman is diagnosed - and this makes imaging and treatment challenging. 

The research was funded by Cancer Research UK.

Reference: Chia, M L: ‘Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment.’ Oncogene, December 2024. DOI: 10.1038/s41388-024-03231-w

An MRI-based imaging technique developed at the University of Cambridge predicts the response of ovarian cancer tumours to treatment, and rapidly reveals how well treatment is working, in patient-derived cell models.

We can image a tumour pre-treatment to predict how likely it is to respond, and then we can image again immediately after treatment to confirm whether it has indeed respondedKevin Brindle

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Yes

“Manifest” was looked up almost 130,000 times on the Cambridge Dictionary website, making it one of the most-viewed words of 2024.  

The word jumped from use in the self-help community and on social media to being widely used across mainstream media and beyond, as celebrities such as singer Dua Lipa, Olympic sprinter Gabby Thomas and England striker Ollie Watkins spoke of manifesting their success in 2024. 

Mentions of it gained traction during the pandemic and have grown in the years since, especially on TikTok and other social media, where millions of posts and videos used the hashtag #manifest.

They use “to manifest” in the sense of: ‘to imagine achieving something you want, in the belief that doing so will make it more likely to happen’. Yet, manifesting is an unproven idea that grew out of a 100-year-old spiritual philosophy movement.

Wendalyn Nichols, Publishing Manager of the Cambridge Dictionary, said: “When we choose a Cambridge Dictionary Word of the Year, we have three considerations: What word was looked up the most, or spiked? Which one really captures what was happening in that year? And what is interesting about this word from a language point of view?

“Manifest” won this year because it increased notably in lookups, its use widened greatly across all types of media due to events in 2024, and it shows how the meanings of a word can change over time.”  

However experts warn that "manifesting” has no scientific validity, despite its popularity. It can lead to risky behaviour or the promotion of false and dangerous beliefs, such as that diseases can be simply wished away.

“Manifesting is what psychologists call ‘magical thinking’ or the general illusion that specific mental rituals can change the world around us," said Cambridge University social psychologist Dr Sander van der Linden, author of The Psychology of Misinformation.

“Manifesting gained tremendous popularity during the pandemic on TikTok with billions of views, including the popular 3-6-9 method which calls for writing down your wishes three times in the morning, six times in the afternoon and nine times before bed. This procedure promotes obsessive and compulsive behaviour with no discernible benefits. But can we really blame people for trying it, when prominent celebrities have been openly ‘manifesting’ their success?  

“’Manifesting’ wealth, love, and power can lead to unrealistic expectations and disappointment. Think of the dangerous idea that you can cure serious diseases simply by wishing them away," said Van der Linden.

“There is good research on the value of positive thinking, self-affirmation, and goal-setting. Believing in yourself, bringing a positive attitude, setting realistic goals, and putting in the effort pays off because people are enacting change in the real world. However, it is crucial to understand the difference between the power of positive thinking and moving reality with your mind – the former is healthy, whereas the latter is pseudoscience.” 

‘Manyfest’, manifest destiny, and manifestos 

The 600-year history of the word “manifest” shows how the meanings of a word can evolve.

The oldest sense – which Geoffrey Chaucer spelled as “manyfest” in the 14th century – is the adjective meaning ‘easily noticed or obvious’.   

In the mid-1800s, this adjective sense was used in American politics in the context of “manifest destiny”, the belief that American settlers were clearly destined to expand across North America.  

Chaucer also used the oldest sense of the verb “manifest”, ‘to show something clearly, through signs or actions’. Shakespeare used manifest as an adjective in The Merchant of Venice: “For it appears, by manifest proceeding, that...thou hast contrived against the very life of the defendant”.  

The verb is still used frequently in this way: for example, people can manifest their dissatisfaction, or symptoms of an illness can manifest themselves. Lack of confidence in a company can manifest itself through a fall in share price.  

The meaning of making something clear is reflected in the related noun “manifesto”: a ‘written statement of the beliefs, aims, and policies of an organization, especially a political party’ – a word that also resonated in 2024 as scores of nations, including the United Kingdom and India, held elections where parties shared manifestos.  

Other words of 2024 

The Cambridge Dictionary is the world’s most popular dictionary for learners of the English language. Increases and spikes in lookups reflect global events and trends. Beyond “manifest”, other popular terms in 2024 included: 

brat: a child, especially one who behaves badly  

“Brat” went viral in the summer of 2024 thanks to pop artist Charli XCX’s album of the same name about nonconformist women who reject a narrow and highly groomed female identity as portrayed on social media. (We weren’t the only dictionary publisher to notice this.) 

demure: quiet and well behaved 

Influencer Jools Lebron’s satirical use of “demure” in a TikTok post mocking stereotypical femininity drove lookups in the Cambridge Dictionary.  After brat summer, we had a demure fall. 

Goldilocks: used to describe a situation in which something is or has to be exactly right  

Financial reporters characterized India’s strong growth and moderate inflation as a Goldilocks economy in early 2024.  

ecotarian: a person who only eats food produced or prepared in a way that does not harm the environment  

This term rose in overall lookups in 2024, reflecting growing interest in environmentally conscious living.  

New words, future entries?   

All year round, Cambridge Dictionary editors track the English language as it changes. Newly emerging words that are being considered for entry are shared every Monday on the Cambridge Dictionary blog, About Words. 

Words Cambridge began tracking in 2024 include: 

quishing: the scam of phishing via QR code. 

resenteeism: to continue doing your job but resent it. This blend of “resent” and “absenteeism” is appearing in business journalism.  

gymfluencer: a social media influencer whose content is focused on fitness or bodybuilding. 

cocktail party problem (also cocktail party effect): the difficulty of focusing on one voice when there are multiple speakers in the room. This term from audiology is now being used with reference to AI. 

vampire: a vampire device or vampire appliance is one which uses energy even when not in use. This is a new, adjective sense of an existing word.  

Adapted from the Cambridge University Press & Assessment website. 

The controversial global trend of manifesting has driven Cambridge Dictionary’s Word of the Year for 2024.

Why psychologists warn against manifesting - Cambridge Dictionary Word of the Year Getty images A marathon runner celebrates the moment he crosses the marathon finish line

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Yes

People in their late teens experience an increased sensitivity to threats after just a few hours left in a room on their own – an effect that endures even if they are interacting online with friends and family.

This is according to latest findings from a cognitive neuroscience experiment conducted at the University of Cambridge, which saw 40 young people aged 16-19 undergo testing before and after several hours alone – both with and without their smartphones.

Many countries have declared an epidemic of loneliness*. The researchers set out to “induce” loneliness in teenagers and study the effects through a series of tests, from a Pavlovian task to electrodes that measure sweat. 

Scientists found that periods of isolation, including those in which participants could use their phones, led to an increased threat response – the sensing of and reacting to potential dangers. This alertness can cause people to feel anxious and uneasy.

The authors of the study say that isolation and loneliness might lead to excessive “threat vigilance”, even when plugged in online, which could negatively impact adolescent mental health over time.

They say it could contribute to the persistent and exaggerated fear responses typical of anxiety disorders on the rise among young people around the world.

While previous studies show isolation leads to anxious behaviour and threat responses in rodents, this is believed to be the first study to demonstrate these effects through experiments involving humans.

The findings are published today in the journal Royal Society Open Science.

“We detected signs of heightened threat vigilance after a few hours of isolation, even when the adolescents had been connected through smartphones and social media,” said Emily Towner, study lead author from Cambridge’s Department of Psychology.

“This alertness to perceived threats might be the same mechanism that leads to the excessive worry and inability to feel safe which characterises anxiety,” said Towner, a Gates Cambridge Scholar.   

“It makes evolutionary sense that being alone increases our vigilance to potential threats. These threat response mechanisms undergo a lot of changes in adolescence, a stage of life marked by increasing independence and social sensitivity.”

"Our experiment suggests that periods of isolation in adolescents might increase their vulnerability to the development of anxiety, even when they are connected virtually.”

Researchers recruited young people from the local area in Cambridge, UK, conducting extensive screening to create a pool of 18 boys and 22 girls who had good social connections and no history of mental health issues.

Participants were given initial tests and questionnaires to establish a “baseline”. These included the Pavlovian threat test, in which they were shown a series of shapes on a screen, one of which was paired with a harsh noise played through headphones, so the shape became associated with a feeling of apprehension.

Electrodes attached to fingers monitored “electrodermal activity” – a physiological marker of stress – throughout this test.**

Each participant returned for two separate stints of around four hours isolated in a room in Cambridge University’s Psychology Department, after which the tests were completed again. There was around a month, on average, between sessions.

All participants underwent two isolation sessions. One was spent with a few puzzles to pass the time, but no connection to the outside world. For the other, participants were allowed smartphones and given wi-fi codes, as well as music and novels. The only major rule in both sessions was they had to stay awake.***

“We set out to replicate behaviour in humans that previous animal studies had found after isolation,” said Towner. “We wanted to know about the experience of loneliness, and you can’t ask animals how lonely they feel.”

Self-reported loneliness increased from baseline after both sessions. It was lower on average after isolation with social media, compared to full isolation.****

However, participants found the threat cue – the shape paired with a jarring sound – more anxiety-inducing and unpleasant after both isolation sessions, with electrodes also measuring elevated stress activity.

On average across the study, threat responses were 70% higher after the isolation sessions compared to the baseline, regardless of whether participants had been interacting digitally.

“Although virtual social interactions helped our participants feel less lonely compared to total isolation, their heightened threat response remained,” said Towner.

Previous studies have found a link between chronic loneliness and alertness to threats. The latest findings support the idea that social isolation may directly contribute to heightened fear responses, say researchers.  

Dr Livia Tomova, co-senior author and lecturer in Psychology at Cardiff University, who conducted the work while at Cambridge, added: “Loneliness among adolescents around the world has nearly doubled in recent years. The need for social interaction is especially intense during adolescence, but it is not clear whether online socialising can fulfil this need.

“This study has shown that digital interactions might not mitigate some of the deep-rooted effects that isolation appears to have on teenagers.”

Scientists say the findings might shed light on the link between loneliness and mental health conditions such as anxiety disorders, which are on the rise in young people.

Notes

*For example, in 2023 the U.S. Surgeon General declared an epidemic of loneliness and isolation.

**Electrodes placed on the fingers record small deflections in sweat and subsequent changes in electrical conductivity of the skin (electrodermal activity). Electrodermal activity is used to detect stress levels and increases with emotional or physical arousal.

***The baseline tests were always taken first. The order of the two isolation sessions was randomly allocated. For sessions with digital interactions allowed, most participants used social media (35 out of 40), with texting being the most common form of interaction (37 out of 40). Other popular platforms included Snapchat, Instagram, and WhatsApp. Participants mainly connected virtually with friends (38), followed by family (19), romantic partners (13), and acquaintances (4).

**** Average self-reported loneliness more than doubled after the isolation session with social media compared to baseline and nearly tripled after the complete isolation session compared to baseline.

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Yes

Data also suggests that Democrat appeals to unity were popular across the board, but “politicians need to do more to understand why some people feel under threat”. 

Researchers in the UK Dementia Research Institute at the University of Cambridge screened more than 1,400 clinically-approved drug compounds using zebrafish genetically engineered to make them mimic so-called tauopathies. They discovered that drugs known as carbonic anhydrase inhibitors – of which the glaucoma drug methazolamide is one – clear tau build-up and reduce signs of the disease in zebrafish and mice carrying the mutant forms of tau that cause human dementias.

Tauopathies are neurodegenerative diseases characterised by the build-up in the brain of tau protein ‘aggregates’ within nerve cells. These include forms of dementia, Pick's disease and progressive supranuclear palsy, where tau is believed to be the primary disease driver, and Alzheimer’s disease and chronic traumatic encephalopathy (neurodegeneration caused by repeated head trauma, as has been reported in football and rugby players), where tau build-up is one consequence of disease but results in degeneration of brain tissue.

There has been little progress in finding effective drugs to treat these conditions. One option is to repurpose existing drugs. However, drug screening – where compounds are tested against disease models – usually takes place in cell cultures, but these do not capture many of the characteristics of tau build-up in a living organism.

To work around this, the Cambridge team turned to zebrafish models they had previously developed. Zebrafish grow to maturity and are able to breed within two to three months and produce large numbers of offspring. Using genetic manipulation, it is possible to mimic human diseases as many genes responsible for human diseases often have equivalents in the zebrafish.

In a study published today in Nature Chemical Biology, Professor David Rubinsztein, Dr Angeleen Fleming and colleagues modelled tauopathy in zebrafish and screened 1,437 drug compounds. Each of these compounds has been clinically approved for other diseases.

Dr Ana Lopez Ramirez from the Cambridge Institute for Medical Research, Department of Physiology, Development and Neuroscience and the UK Dementia Research Institute at the University of Cambridge, joint first author, said: “Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organisms. They also enable us to do so at scale, something that it not feasible or ethical in larger animals such as mice.”  

Using this approach, the team showed that inhibiting an enzyme known as carbonic anhydrase – which is important for regulating acidity levels in cells – helped the cell rid itself of the tau protein build-up. It did this by causing the lysosomes – the ‘cell’s incinerators’ – to move to the surface of the cell, where they fused with the cell membrane and ‘spat out’ the tau.

When the team tested methazolamide on mice that had been genetically engineered to carry the P301S human disease-causing mutation in tau, which leads to the progressive accumulation of tau aggregates in the brain, they found that those treated with the drug performed better at memory tasks and showed improved cognitive performance compared with untreated mice.

Analysis of the mouse brains showed that they indeed had fewer tau aggregates, and consequently a lesser reduction in brain cells, compared with the untreated mice.

Fellow joint author Dr Farah Siddiqi, also from the Cambridge Institute for Medical Research and the UK Dementia Research Institute, said: “We were excited to see in our mouse studies that methazolamide reduces levels of tau in the brain and protects against its further build-up. This confirms what we had shown when screening carbonic anhydrase inhibitors using zebrafish models of tauopathies.”

Professor Rubinsztein from the UK Dementia Research Institute and Cambridge Institute for Medical Research at the University of Cambridge, said: “Methazolamide shows promise as a much-needed drug to help prevent the build-up of dangerous tau proteins in the brain. Although we’ve only looked at its effects in zebrafish and mice, so it is still early days, we at least know about this drug’s safety profile in patients. This will enable us to move to clinical trials much faster than we might normally expect if we were starting from scratch with an unknown drug compound.

“This shows how we can use zebrafish to test whether existing drugs might be repurposed to tackle different diseases, potentially speeding up significantly the drug discovery process.”

The team hopes to test methazolamide on different disease models, including more common diseases characterised by the build-up of aggregate-prone proteins, such as Huntington’s and Parkinson’s diseases.

The research was supported by the UK Dementia Research Institute (through UK DRI Ltd, principally funded through the Medical Research Council), Tau Consortium and Wellcome.

Reference
Lopez, A & Siddiqi, FH et al. Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion. Nat Chem Bio; 31 Oct 2024; DOI: 10.1038/s41589-024-01762-7
 

A drug commonly used to treat glaucoma has been shown in zebrafish and mice to protect against the build-up in the brain of the protein tau, which causes various forms of dementia and is implicated in Alzheimer’s disease.

Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organismsAna Lopez RamirezKuznetsov_PeterZebrafish

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The research team, led by the University of Cambridge, adapted an algorithm originally designed for humans and found it could automatically detect and grade heart murmurs in dogs, based on audio recordings from digital stethoscopes. In tests, the algorithm detected heart murmurs with a sensitivity of 90%, a similar accuracy to expert cardiologists.

Heart murmurs are a key indicator of mitral valve disease, the most common heart condition in adult dogs. Roughly one in 30 dogs seen by a veterinarian has a heart murmur, although the prevalence is higher in small breed dogs and older dogs.

Since mitral valve disease and other heart conditions are so common in dogs, early detection is crucial as timely medication can extend their lives. The technology developed by the Cambridge team could offer an affordable and effective screening tool for primary care veterinarians, and improve quality of life for dogs. The results are reported in the Journal of Veterinary Internal Medicine.

“Heart disease in humans is a huge health issue, but in dogs it’s an even bigger problem,” said first author Dr Andrew McDonald from Cambridge’s Department of Engineering. “Most smaller dog breeds will have heart disease when they get older, but obviously dogs can’t communicate in the same way that humans can, so it’s up to primary care vets to detect heart disease early enough so it can be treated.”

Professor Anurag Agarwal, who led the research, is a specialist in acoustics and bioengineering. “As far as we’re aware, there are no existing databases of heart sounds in dogs, which is why we started out with a database of heart sounds in humans,” he said. “Mammalian hearts are fairly similar, and when things go wrong, they tend to go wrong in similar ways.”

The researchers started with a database of heart sounds from about 1000 human patients and developed a machine learning algorithm to replicate whether a heart murmur had been detected by a cardiologist. They then adapted the algorithm so it could be used with heart sounds from dogs.

The researchers gathered data from almost 800 dogs who were undergoing routine heart examination at four veterinary specialist centres in the UK. All dogs received a full physical examination and heart scan (echocardiogram) by a cardiologist to grade any heart murmurs and identify cardiac disease, and heart sounds were recorded using an electronic stethoscope. By an order of magnitude, this is the largest dataset of dog heart sounds ever created.

“Mitral valve disease mainly affects smaller dogs, but to test and improve our algorithm, we wanted to get data from dogs of all shapes, sizes and ages,” said co-author Professor Jose Novo Matos from Cambridge’s Department of Veterinary Medicine, a specialist in small animal cardiology. “The more data we have to train it, the more useful our algorithm will be, both for vets and for dog owners.”

The researchers fine-tuned the algorithm so it could both detect and grade heart murmurs based on the audio recordings, and differentiate between murmurs associated with mild disease and those reflecting advanced heart disease that required further treatment.  

“Grading a heart murmur and determining whether the heart disease needs treatment requires a lot of experience, referral to a veterinary cardiologist, and expensive specialised heart scans,” said Novo Matos. “We want to empower general practitioners to detect heart disease and assess its severity to help owners make the best decisions for their dogs.”

Analysis of the algorithm’s performance found it agreed with the cardiologist’s assessment in over half of cases, and in 90% of cases, it was within a single grade of the cardiologist’s assessment. The researchers say this is a promising result, as it is common for there to be significant variability in how different vets grade heart murmurs.

“The grade of heart murmur is a useful differentiator for determining next steps and treatments, and we’ve automated that process,” said McDonald. “For vets and nurses without as much stethoscope skill, and even those who are incredibly skilled with a stethoscope, we believe this algorithm could be a highly valuable tool.”

In humans with valve disease, the only treatment is surgery, but for dogs, effective medication is available. “Knowing when to medicate is so important, in order to give dogs the best quality of life possible for as long as possible,” said Agarwal. “We want to empower vets to help make those decisions.”

“So many people talk about AI as a threat to jobs, but for me, I see it as a tool that will make me a better cardiologist,” said Novo Matos. “We can’t perform heart scans on every dog in this country  – we just don’t have enough time or specialists to screen every dog with a murmur. But tools like these could help vets and owners, so we can quickly identify those dogs who are most in need of treatment.”

The research was supported in part by the Kennel Club Charitable Trust, the Medical Research Council, and Emmanuel College Cambridge.

Reference:
Andrew McDonald et al. ‘A machine learning algorithm to grade canine heart murmurs and stage preclinical myxomatous mitral valve disease.’ Journal of Veterinary Internal Medicine (2024). DOI: 10.1111/jvim.17224

Researchers have developed a machine learning algorithm to accurately detect heart murmurs in dogs, one of the main indicators of cardiac disease, which affects a large proportion of some smaller breeds such as King Charles Spaniels.

Jacqueline GargetHuxley, a healthy volunteer Havanese, undergoes a physical examination at the Queen's Veterinary School Hospital, Cambridge.

The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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