Publisher Health

Radon is the second leading cause of lung cancer. Now a new study has found exposure to this invisible, odorless gas is also linked to an increased risk of stroke. The study, which examined exposures in middle age to older female participants, found an increased risk of stroke among those exposed to high and even moderate concentrations of the gas compared to those exposed to the lowest concentrations. The study is published in the January 31, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that exposure to radon causes stroke; it only shows an association.
Radon is a naturally occurring radioactive gas produced when metals like uranium or radium break down in rocks and soil. The gas can make its way into homes through cracks in basement walls and floors, construction joints and gaps around pipes.
“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” said study author Eric A. Whitsel, MD, MPH, of the University of North Carolina in Chapel Hill. “Our research found an increased risk of stroke among participants exposed to radon above — and as many as two picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system.”
The study involved 158,910 female participants with an average age of 63 who did not have stroke at the start of the study. They were followed for an average of 13 years. During the study, there were 6,979 strokes among participants.
To determine radon exposures, researchers linked participants’ home addresses to radon concentration data from the U.S. Geological Survey and the U.S. Environmental Protection Agency (EPA).
The EPA recommends that average indoor radon concentrations do not exceed four picocuries per liter (pCi/L). For concentrations this high, the EPA recommends installing a radon mitigation system to lower radon levels in the home.
Participants were divided into three groups. The highest group had homes in areas where average radon concentrations were more than four pCi/L. The middle group lived in areas with average concentrations between two and four pCi/L. The lowest group lived in areas with average concentrations of less than two pCi/L.

In the group with the highest radon exposures, there were 349 strokes per 100,000 person-years compared to 343 strokes in the middle group and 333 strokes in group with the lowest exposure. Person-years represent both the number of people in the study and the amount of time each person spends in the study.
After adjusting for factors such as smoking, diabetes and high blood pressure, researchers found participants in the highest group had a 14% increased risk of stroke compared to those in the lowest group. Those in the middle group had a 6% increased risk.
“It’s important to note that we found an increased stroke risk among those exposed to radon concentrations as much as two pCi/L below the current lung cancer-based threshold for recommending radon mitigation,” said Whitsel. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”
A limitation of the study was that it included only female participants who were middle age or older and primarily white, so the results may not be the same for other populations.
The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute.

People with polycystic ovary syndrome may be more likely to have memory and thinking problems in middle age, according to new research published in the January 31, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that polycystic ovary syndrome causes cognitive decline. It only shows an association.
Polycystic ovary syndrome is a hormonal disorder that is defined by irregular menstruation and elevated levels of a hormone called androgen. Other symptoms may include excess hair growth, acne, infertility and poor metabolic health.
“Polycystic ovary syndrome is a common reproductive disorder that impacts up to 10% of women,” said study author Heather G. Huddleston, MD, of the University of California, San Francisco. “While it has been linked to metabolic diseases like obesity and diabetes that can lead to heart problems, less is known about how this condition affects brain health. Our results suggest that people with this condition have lower memory and thinking skills and subtle brain changes at midlife. This could impact a person on many levels, including quality of life, career success and financial security.”
The study involved 907 female participants who were 18 to 30 years old at the start of the study. They were followed for 30 years, at which time they completed tests to measure memory, verbal abilities, processing speed and attention.
At the time of testing, 66 participants had polycystic ovary syndrome.
In a test measuring attention, participants looked at a list of words in different colors and were asked to state the color of the ink rather than read the actual word. For example, the word “blue” could be displayed in red, so the correct response would be red.
Researchers found for this test, people with polycystic ovary syndrome had an average score that was approximately 11% lower compared to people without the condition.

After adjusting for age, race and education, researchers found that people with polycystic ovary syndrome had lower scores on three of the five tests that were given, specifically in areas of memory, attention and verbal abilities, when compared to those without this condition.
At years 25 and 30 of the study, a smaller group of 291 participants had brain scans. Of those, 25 had polycystic ovary syndrome. With the scans, researchers looked at the integrity of the white matter pathways in the brain by looking at movement of water molecules in the brain tissue.
Researchers found that people with polycystic ovary syndrome had lower white matter integrity, which may indicate early evidence of brain aging.
“Additional research is needed to confirm these findings and to determine how this change occurs, including looking at changes that people can make to reduce their chances of thinking and memory problems,” Huddleston said. “Making changes like incorporating more cardiovascular exercise and improving mental health may serve to also improve brain aging for this population.”
A limitation of the study was that polycystic ovary syndrome diagnosis was not made by a doctor but was based on androgen levels and self-reported symptoms, so participants may not have remembered all the information accurately.
The study was funded by the University of California, San Francisco.

Type 2 diabetes is associated with increased risk of kidney stones, but some forms of treatment for this condition may also have the benefit of lowering risk of kidney stones. In a study led by investigators from Mass General Brigham, researchers found that there was an association between the use of sodium-glucose contratransporter 2 (SGLT2) inhibitors and a lower risk of developing kidney stones. Their findings are reported in JAMA Internal Medicine.
Rates of kidney stones are on the rise in the United States and around the world. Type 2 diabetes is associated with increased risk of kidney stones, but some forms of treatment for this condition may also have the benefit of lowering risk of kidney stones. In a study led by investigators from Mass General Brigham, researchers found that there was an association between the use of sodium-glucose contratransporter 2 (SGLT2) inhibitors and a lower risk of developing kidney stones. Their findings are reported in JAMA Internal Medicine.
Researchers from Brigham and Women’s Hospital and Massachusetts General Hospital, founding members of the Mass General Brigham healthcare system, worked together to conduct the analysis. The study included data from three nationwide databases of patients with type 2 diabetes who were seen in routine clinical practice. The team analyzed information from 716,406 adults with type 2 diabetes who had started taking an SGLT2 inhibitor or two other classes of diabetes medications known as GLP1 receptor agonists or dipeptidyl peptidase 4 (DPP4) inhibitors. Patients who began taking SGLT2 inhibitors had a 30 percent lower risk of developing kidney stones than those taking GLP1 agonists and about a 25 percent lower risk than those taking DPP4 inhibitors. The findings were consistent across sex, race/ethnicity, history of chronic kidney disease and obesity.
“Our findings could help inform clinical decision making for patients with diabetes who are at risk for developing kidney stones,” said corresponding author Julie Paik, MD, ScD, MPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney) Medicine at Brigham and Women’s Hospital.

You might think age-related dementia has been with us all along, stretching back to the ancient world.
But a new analysis of classical Greek and Roman medical texts suggests that severe memory loss — occurring at epidemic levels today — was extremely rare 2,000 to 2,500 years ago, in the time of Aristotle, Galen and Pliny the Elder.
The USC-led research, published in the Journal of Alzheimer’s Disease, bolsters the idea that Alzheimer’s disease and related dementias are diseases of modern environments and lifestyles, with sedentary behavior and exposure to air pollution largely to blame.
“The ancient Greeks had very, very few — but we found them — mentions of something that would be like mild cognitive impairment,” said first author Caleb Finch, a University Professor at the USC Leonard Davis School of Gerontology. “When we got to the Romans, and we uncovered at least four statements that suggest rare cases of advanced dementia — we can’t tell if it’s Alzheimer’s. So, there was a progression going from the ancient Greeks to the Romans.”
Ancient Greeks recognized that aging commonly brought memory issues we would recognize as mild cognitive impairment, or MCI, but nothing approaching a major loss of memory, speech and reasoning as caused by Alzheimer’s and other types of dementia.
Finch and co-author Stanley Burstein, a historian at California State University, Los Angeles, pored over a major body of ancient medical writing by Hippocrates and his followers. The text catalogs ailments of the elderly such as deafness, dizziness and digestive disorders — but makes no mention of memory loss.
Centuries later in ancient Rome, a few mentions crop up. Galen remarks that at the age of 80, some elderly begin to have difficulty learning new things. Pliny the Elder notes that the senator and famous orator Valerius Messalla Corvinus forgot his own name. Cicero prudently observed that “elderly silliness … is characteristic of irresponsible old men, but not of all old men.”
Finch speculates that as Roman cities grew denser, pollution increased, driving up cases of cognitive decline. In addition, Roman aristocrats used lead cooking vessels, lead water pipes and even added lead acetate into their wine to sweeten it — unwittingly poisoning themselves with the powerful neurotoxin.

(A few ancient writers recognized the toxicity of lead-containing material, but little progress was made in dealing with the problem until well into the 20th century. Some scholars blame lead poisoning for the fall of the Roman Empire.)
For this paper, Finch did not just think about the Roman Empire or the Greeks. In the absence of demographic data for ancient Greece and Rome, Finch turned to a surprising model for ancient aging: today’s Tsimane Amerindians, an Indigenous people of the Bolivian Amazon.
The Tsimane — like the ancient Greeks and Romans — have a preindustrial lifestyle that is very physically active, and they have extremely low rates of dementia. An international team of cognitive researchers led by Margaret Gatz, a professor of psychology, gerontology and preventive medicine at the USC Leonard Davis School, found among older Tsimane people, only about 1% suffer from dementia. In contrast, 11% of people aged 65 and older living in the United States have dementia, according to the Alzheimer’s Association.
“The Tsimane data, which is quite deep, is very valuable,” Finch said. “This is the best-documented large population of older people that have minimal dementia, all of which indicates that the environment is a huge determinant on dementia risk. They give us a template for asking these questions.”
The paper was supported by funds from the Cure Alzheimer’s Fund and the National Institutes of Health (P01 AG055367 and R01 AG05442).

The neurons that make up our brains and nervous systems mature slowly over many months. And while this may be beneficial from an evolutionary standpoint, the slow pace makes growing cells to study neurodegenerative and neurodevelopmental diseases — like Parkinson’s disease, Alzheimer’s disease, and autism — in the laboratory quite challenging.
Currently, nerve cells derived from human pluripotent stem cells take months to reach an adultlike state in the lab — a timeline that mirrors the slow pace of human brain development. (“Pluripotent stem cells” have the potential to develop into many other kinds of cells.)
New research led by Memorial Sloan Kettering Cancer Center (MSK), however, has uncovered a way to “hack” the cells’ internal clocks to speed up the process. And the work is shedding new light on how cells’ developmental timetables are regulated.
“This slow pace of nerve cell development has been linked to humans’ unique and complex cognitive abilities,” says Lorenz Studer, MD, Director of MSK’s Center for Stem Cell Biology and the senior author of two recent studies published in Natureand Nature Biotechnology. “Previous research has suggested the presence of a ‘clock’ within cells that sets the pace of our neurons’ development, but its biological nature had largely remained unknown — until now.”
New Insights Into Nerve Cell Development
Researchers, led by study first author Gabriele Ciceri, PhD, identified an epigenetic “barrier” in the stem cells that give rise to neural cells. (“Epigenetic changes” are ones that don’t alter the DNA code.) This barrier acts as a brake on the development process and determines the rate at which the cells mature. By inhibiting the barrier, the scientists were able to speed up the neurons’ development, they reported January 31 in Nature.
(View the related Nature video: Why human brain cells grow so slowly.)
“While studying brain development in mice, I was struck by how neurons progress through a series of steps in a very precise schedule,” says Dr. Ciceri, a senior research scientist in the Studer Lab at MSK’s Sloan Kettering Institute. “But this schedule creates a big practical challenge when working with human neurons — what takes hours and days in the mouse requires weeks and months in human cells.”

Furthermore, the team showed that this rate-setting epigenetic barrier is built into neural stem cells well before they differentiate into different types of neurons. They also found higher levels of the barrier in human neurons compared with mouse neurons, which may help explain differences in the pace of cell maturation in different species.
Uncovering Foundational Biology
That such discoveries were made at a cancer center isn’t as surprising as it might seem at first blush. The Studer Lab has long focused on harnessing advances in stem cell biology to develop new therapies for degenerative diseases and cancer — both of which are strongly associated with aging.
Moreover, MSK has long been a leader in “basic science” research — that is, science that seeks to build fundamental understanding of human biology.
About half of the National Institutes of Health (NIH) budget goes to funding basic science research. And the vast majority of drugs approved by the Food and Drug Administration in recent years involved publicly funded basic research, according to the NIH.
“All of the major advances in cancer treatment in recent years — immune checkpoint inhibitor therapy, CAR T cell therapy, cancer vaccines — they’re all rooted in basic research,” says Joan Massagué, PhD, Director of the Sloan Kettering Institute and MSK’s Chief Scientific Officer. “Sometimes it can take years for the medical relevance of a particular discovery to become clear.”
‘A Valuable Research Tool’

A second study, led by Studer Lab graduate students Emiliano Hergenreder and Andrew Minotti and published January 2 in Nature Biotechnology, identified a combination of four chemicals that together can promote neuronal maturation. Dubbed GENtoniK, the chemical cocktail both represses epigenetic factors that inhibit cell maturation and stimulates factors that promote it.
Along with helping to bring neurons to an adultlike state faster in the lab, the approach holds promise for other cell types, the researchers note.
Not only was GENtoniK shown to speed the maturation of cortical neurons (involved in cognitive functions) and spinal motor neurons (involved in movement), but the chemicals were also able to accelerate the development of several other types of cells derived from stem cells, including melanocytes (pigment cells) and pancreatic beta cells (endocrine cells).
“The generation of human neurons in a dish from stem cells provides a unique inroad into the study of brain health and disease,” the journal editors note in a research briefing that accompanied the study. “A major obstacle in the field arises from the fact that human neurons require many months to mature during development, making it difficult to recapitulate the process in vitro. The authors provide a valuable research tool by developing a simple drug cocktail that speeds up the maturation timeframe.”
The findings could be particularly helpful in modeling disorders like autism that involve problems with synaptic connectivity, Dr. Studer says.
Still, he notes, additional research is needed to develop models of neurodegenerative disorders that don’t occur until very late in life, such as Parkinson’s disease, which has long been a focus of Studer’s research.
“Typically, a person is 60 to 70 years old when the disease begins. No baby gets Parkinson’s,” he says. “So, for those diseases, we need to be able to put the cells not just into an adult state but into an aged-like state. That’s something we’re continuing to work on.”

Indiana University researchers in the College of Arts and Sciences in Bloomington have identified a missing link that can help protect the brain from aging.
Hui-Chen Lu, professor and director of the Linda and Jack Gill Center for Biomolecular Science at IU, alongside graduate students Sen Yang and Zhen Xian Niou, found that nicotinamide nucleotide adenylyl transferase 2, or NMNAT2, provides energy to axons independent of the mitochondria. It does this by propelling glycolysis, a process in which glucose is broken down to produce energy. This gives axons enough energy to carry out nerve impulses to the brain and other parts of the body, keeping them healthy and functional. The enzyme can play a critical role in fending off neurodegenerative diseases like ALS, Alzheimer’s, Huntington’s and Parkinson’s as people age.
The study can be found in Molecular Neurodegeneration.
Axons are long, thin fibers that connect nerve cells and allow them to communicate with each other. Axons are typically one micrometer in diameter — several times thinner than a human hair — making them vulnerable and easily damaged by inflammation, trauma, reduced blood flow to the brain and infection. Often, axon damage is the first sign of neurodegenerative disease, but their protection can delay neurodegeneration.
Axons quickly convey information throughout the entire body, a process of traveling long distances within an extremely short time scale that requires significant amounts of energy. However, the mitochondria, widely known as the cellular powerhouse, are in relatively sparse density in axons.
NMNAT2 is a vital provider of nicotinamide adenine dinucleotide for the brain. NAD has been studied intensively for its regenerative properties and is sometimes referred to as the “fountain of youth.”
“This new finding showcases the importance of neuron-intrinsic glycolysis in supporting axonal transport, essential for the establishment and maintenance of neuronal circuitry,” Lu said. “With this information, the next step could be designing drugs to target NMNAT2 to boost its expression or activity in pre-symptomatic stages of neurodegeneration.”
Lu’s laboratory has studied NMNAT2 extensively, publishing research in 2017 which found that caffeine, along with 23 other compounds, can increase the body’s production of NMNAT2. In 2016, Lu published a study that found those with higher levels of NMNAT2 had greater resistance to cognitive decline as they aged.

Rickets ran rife in children following the Industrial Revolution, but University of Otago-led research has found factory work and polluted cities aren’t entirely to blame for the period’s vitamin D deficiencies.
In a Marsden funded study, just published in PLOS One, researchers from Otago, Durham University, University of Edinburgh, University of Brighton, and University of Queensland, sampled teeth from a cemetery site in industrial era England, looking for microscopic markers of nutritional disease.
Lead author Dr Annie Sohler-Snoddy, Research Fellow in Otago’s Department of Anatomy, says they uncovered some of the first clear evidence of seasonal vitamin D deficiency in an archaeological sample.
She says it has been known for many years that there was an increase in rickets, a childhood bone disease caused by vitamin D deficiency, in 18th and 19th Century Europe.
“It has been assumed that this was due to more people, including children, working long hours indoors, living in crowded housing and in smog-filled environments, all of which reduce the amount of sunlight that reaches a person’s skin, which is the main way humans make vitamin D.”
However, new bioarchaeological methods enabled the researchers to get a much clearer picture of how vitamin D deficiency affected the people living in industrial England, rather than looking at bone deformities alone.
The study found markers associated with vitamin D deficiency in the interior part of 76 per cent of the teeth analysed. In many samples, these occurred regularly, in annual increments.

“This shows clear evidence of seasonal vitamin D deficiency in the teeth of people living in the north of England.
“This is exciting because it highlights that latitude and seasonal lack of sunlight was a major factor in the amount of vitamin D these people could make in their skin — it’s more complicated than the factors associated with the industrial revolution like working indoors more,” Dr Sohler-Snoddy explains.
Poor vitamin D status is associated with several negative health outcomes including increased risk for infectious diseases, cardiovascular disease, and cancers.
Vitamin D deficiency has been an ongoing problem in society and Dr Sohler-Snoddy believes it is important to study what happened in the past in order to inform modern approaches to the ailment.
“We tend to think of archaeological human remains as belonging to a different world, but our biology hasn’t changed in the last 200 years.
“Teeth provide a really important source of information for archaeologists as they form in a very precise chronology and, importantly, their tissues do not change over the lifespan. This means that they lock in a record of a person’s development and this stays with them until they die, or the tooth is lost.
“Understanding how vitamin D deficiency impacted past populations and why gives us an important deep-time perspective on the disease,” she says.

In a rare but serious complication of cancer, the body’s own immune system can start attacking the brain, causing rapid-onset memory loss and cognitive deficits. What triggers this sudden biological civil war was largely unknown. Now, researchers at University of Utah Health have found that some tumors can release a protein that looks like a virus, kickstarting an out-of-control immune reaction that may damage brain cells.
Their findings published in Cell on Jan. 31, 2024.
A rapid immune attack
Jason Shepherd, Ph.D., associate professor of neurobiology at University of Utah Health and last author on the study, explains that the swift escalation of symptoms — which can include memory and behavioral changes, loss of coordination, and even seizures — is a hallmark of the disease, called anti-Ma2 paraneoplastic neurological syndrome. The disease is one of a group of cancer-related neurological syndromes that occur in less than one in 10,000 people with cancer. The precise symptoms of these diseases vary, but all involve rapid immune reactions against the nervous system. “The symptoms come in quickly and can be quite debilitating,” Shepherd says.
“This fascinating research illustrates how tumor cells can manipulate their environment,” says Neli Ulrich, Ph.D., executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute at the University of Utah and a Jon M. and Karen Huntsman Presidential Professor in Cancer Research at the U. “We hope that this innovative transdisciplinary research will positively impact both the lives of cancer patients and of those who experience neurological symptoms.”
Stacey L. Clardy, M.D., Ph.D., a neurologist at U of U Health and a coauthor on the study, adds, “Most patients begin to experience these unusual neurologic symptoms before they even know they have a cancer.”
These rapid-onset symptoms are the result of the immune system suddenly starting to target specific proteins that are found in the brain. Scientists knew that this flare of immunity often targets a protein called PNMA2. But nobody knew why PNMA2 provokes such a strong immune response, which left researchers at a loss for ways to prevent it. “We do not understand what is happening at the cellular or molecular level to actually cause the syndrome,” Clardy says, “and understanding the mechanism of disease is crucial to developing better treatments.”
A virus lookalike

To figure out how PNMA2 kickstarts an immune reaction, Junjie Xu, a graduate researcher in neurobiology at U of U Health and the lead author on the study, examined the protein’s structure using advanced microscopy. When he saw the first clear image of the protein, he was “so, so excited,” Xu says. Multiple PNMA2 proteins had spontaneously self-organized into 12-sided complexes that bore a striking resemblance to the geometric protein shells of some viruses.
One of the immune system’s healthy functions is to attack viruses, and PNMA2’s virus-like structure makes it particularly prone to being targeted as well, the researchers found. In fact, in experiments in mice, the immune system only attacked PNMA2 protein when it was assembled into virus-like complexes.
Wrong place, wrong time
The location of PNMA2 in the body is also a crucial piece of the puzzle, the scientists found. “This protein normally is only expressed in the brain, in neurons,” Xu says, “but some cancer cells can express it, which can trigger an immune response.”
As long as PNMA2 stays in the brain, the immune system won’t react to it. But rarely, a tumor elsewhere in the body will start producing PNMA2 protein. And when the immune system detects PNMA2 protein outside the brain, it reacts like it would to any foreign invader. The immune system makes antibodies that bind to the unfamiliar substance, and those antibodies direct immune cells to attack.
But, once activated, the immune system doesn’t just attack the PNMA2 produced by the cancer. It also targets the parts of the brain that produce PNMA2 normally, including regions involved in memory, learning, and movement. The brain normally has a degree of protection from the immune system, but cancer weakens that barrier, leaving the brain especially vulnerable to this immune onslaught.
In future work, the researchers aim to figure out which aspect of the immune response leads to patients’ rapid cognitive decline — the antibodies themselves, immune cells making their way into the brain, or some combination of the two.
Understanding how the immune system causes neurological symptoms may help scientists design targeted treatments, Shepherd says. “If we show that PNMA2 antibodies are the culprit that really drives the neurological symptoms, you could devise a way to block those antibodies from getting into the brain or mop them up with something as a treatment… If you can alleviate some of those neurological symptoms, it really would be huge.”

Artificial Intelligence (AI) can predict whether adult patients with brain cancer will survive more than eight months after receiving radiotherapy treatment.
The use of the AI to successfully predict patient outcomes would allow clinicians to be better informed for planning the next stage of treatment and refer patients to potentially life-saving treatment quicker.
This is the first use of AI to predict short-term and long-term survivors within eight-months of radiotherapy.
The paper published recently in Neuro-Oncology shows how researchers from King’s College London created a deep learning model to allow them to more reliably and accurately predict outcomes for patients with adult primary brain cancer.
Glioblastoma is a difficult to treat cancer with just one in four patients surviving more than one year after diagnosis. The researchers applied deep learning — a type of AI — to predict whether glioblastoma patients would survive the eight months after receiving radiotherapy. Eight months is typically the time taken to complete a typical course of routine chemotherapy that usually follows radiotherapy.
Currently, patients are regularly and routinely scanned to see if the chemotherapy is working. But this means that some patients have ineffective chemotherapy which wouldn’t save their life and suffer through harmful side effects.
Instead, by giving an instantaneous and accurate prediction from one routine MRI scan, the AI allows doctors to identify patients who would not benefit from chemotherapy to try a different treatment or start an experimental treatment in a clinical trial.

Dr Thomas Booth, Reader in Neuroimaging at King’s College London and a Neurology Consultant at King’s College Hospital NHS Foundation Trust, said: “This study was motivated by a clinically-attuned and critical research question regarding aggressive brain tumours, and delivered by leveraging cutting edge artificial intelligence. Whilst less common than other cancers, the devastation is disproportionate with a two-year survival rate of 18%.”
Alysha Chelliah, PhD researcher from King’s College London, said: “We applied deep learning to predict whether glioblastoma patients will survive the first eight months after completing radiotherapy. The AI model showed improved performances when first trained to detect abnormalities on 10,000s of brain MRIs. This approach is intended to improve the ability to identify patients who require early second-line treatment or clinical trial enrolment, compared to those showing initial treatment response.”
Researchers trained the AI on a dataset of 10,000s of scans from all types of patients with brain cancer.
Dr Thomas Booth said: “Feedback from all patients and clinicians at the start of the study meant that we wanted to address the unmet need of improving outcomes of the large proportion of patients undergoing modified treatment — usually a shorter course and lower dose of radiotherapy if chemotherapy is not effective — as well as the minority of patients who can tolerate “optimal” treatment. Almost all previous research considers only the latter group of patients.
“We also side-stepped a thorny issue: after radiotherapy, follow-up brain scan findings are often non-specific and oncologists cannot be certain whether a treatment is working or failing.
“Instead of trying to grapple with interpreting each and every non-specific follow-up brain scan, we simply looked at one routine scan after radiotherapy and gave an accurate prediction using artificial intelligence to answer a simple question: which patients will not survive the next 8 months? The AI was able to give us an immediate and accurate prediction which means clinicians can empower patients to make choices about their treatment.”
Dr Booth added: “We would be delighted if the cancer research community now uses our artificial intelligence tool to see improved outcomes for patients who won’t benefit from the usual course of chemotherapy.”

Commenting on how the work of Dr Booth and his team at King’s College London supported people-first brain tumour research as advocated for by the charity brainstrust, Dr Helen Bulbeck, Director of Services and Policy at brainstrust said:
“This is exciting and fundamental research for people living with a glioblastoma, for two reasons. At its simplest level it demonstrates how AI can be used for patient benefit. More importantly however, it empowers patients and their caregivers to make choices about the clinical pathway and gives control back at a time when so much control has been lost. Patients will be able to make informed decisions about treatment choices and will be able to plan how they want to spend the time they have left so that they can live their best possible day, every day.”
Dr Michele Afif, CEO at The Brain Tumour Charity added: “The use of AI to evaluate and predict response to radiotherapy at a much earlier point in a patient’s treatment for glioblastoma is a hugely important step in tackling this notoriously difficult to treat disease.
At The Brain Tumour Charity, we welcome this important advance which could lead to more informed discussions at an early enough point in a patient’s treatment to consider meaningful alternatives, such as clinical trials.
We look forward to seeing how this exciting research progresses as it is validated for wider use as a tool to improve care for those diagnosed with a brain tumour.”
The study involved a collaboration of 11 neuro-oncology centres from across the UK.

Among the most difficult types of pain to alleviate is neuropathic pain, pain that is usually caused by damage to nerves in various body tissues, including skin, muscle and joints. It can cause patients to suffer feelings like electric shocks, tingling, burning or stabbing. Diabetes, multiple sclerosis, chemotherapy drugs, injuries and amputations have all been associated with neuropathic pain, which is often chronic, sometimes unrelenting and affects millions of people worldwide. Many of the available pain medications are only moderately effective at treating this type of pain and often come with serious side effects, as well as risk of addiction.
Now researchers at UT Austin, The University of Texas at Dallas and the University of Miami have identified a molecule that reduces hypersensitivity in trials in mice by binding to a protein they have shown is involved in neuropathic pain.
The findings appear in the journal Proceedings of the National Academy of Sciences.
“We found it to be an effective painkiller, and the effects were rather long-lived,” said Stephen Martin, the June and J. Virgil Waggoner Regents Chair in Chemistry at The University of Texas at Austin and co-corresponding author of the paper. “When we tested it on different models, diabetic neuropathy and chemotherapy-induced neuropathy, for example, we found this compound has an incredible beneficial effect.”
The new compound, dubbed FEM-1689, does not engage opioid receptors in the body, making it a possible alternative to existing pain medications linked to addiction. In addition to reducing sensitivity, the compound can help regulate the integrated stress response (ISR), a network of cellular signaling that helps the body respond to injuries and diseases. When well regulated, the ISR restores balance and promotes healing. When it goes awry, the ISR can contribute to diseases such as cancer, diabetes and metabolic disorders.
“It’s our goal to make this compound into a drug that can be used to treat chronic pain without the dangers of opioids,” Martin said. “Neuropathic pain is often a debilitating condition that can affect people their entire lives, and we need a treatment that is well tolerated and effective.”
NuvoNuro Inc., a company co-founded by Martin and other authors on the paper, was recently awarded a grant from the National Institutes of Health HEAL Initiative, which funds research to find scientific solutions to the national opioid crisis, to create a drug based on their findings.

“This work is the culmination of a wonderful five-year collaboration with our colleagues at UT Austin and is a great example of academic drug discovery pushing the field of non-opioid pain therapeutics forward,” said Theodore Price, a professor of neuroscience at The University of Texas at Dallas and co-corresponding author of the paper. “Our funding from NIH on this continuing project through our spin-out company, NuvoNuro, has the potential to take us toward clinical development in the next few years, which is extraordinarily exciting.”
Muhammad Saad Yousuf, Eric T. David, Stephanie Shiers, Marisol Mancilla Moreno, Jonathan Iketem, Danielle M. Royer, Chelsea D. Garcia, Jennifer Zhang, Veronica M. Hong, Subhaan M. Mian, Ayesha Ahmad and Benedict J. Kolber of The University of Texas at Dallas; James J. Sahn and Hongfen Yang of UT Austin; and Daniel J. Liebl of University of Miami Miller School of Medicine were also authors on the paper.
The research was funded by the National Institutes of Health, Natural Sciences and Engineering Research Council of Canada and the Robert A. Welch Foundation.
The University of Texas at Austin is committed to transparency and disclosure of all potential conflicts of interest. University investigators involved in this research have submitted required financial disclosure forms with the University. As co-founders of NuvoNuro Inc., Stephen Martin and James Sahn also are co-inventors on patents and pending patent applications related to work described in this article.