Publisher Health

New research published today suggests there is a link between abnormal blood levels of amyloid — a protein associated with Alzheimer’s disease — and subtle changes in brain microstructures on a type of MRI, findings that could lead to a new way to detect Alzheimer’s earlier in people with no clinical signs.
Researchers analyzed the results of 128 human participants with and without dementia from the 1Florida Alzheimer’s Disease Research Center who underwent imaging scans using an established diagnostic tool called positron emission tomography, or PET, which can detect amyloid plaques in the brain, a hallmark of Alzheimer’s disease.
Even when a PET scan was negative for amyloid and a participant free of dementia symptoms, researchers found there was an association in those who showed abnormal amyloid levels in the blood and structural abnormalities in the brain detected through a newer method called diffusion MRI, also known as “free-water” imaging.
A team led by investigators from UF’s Evelyn F. and William L. McKnight Brain Institute and the Norman Fixel Institute for Neurological Diseases at UF Health reported that the results represent a novel finding that free-water imaging is sensitive to early stages of decline in brain tissue and tiny structures in key parts of the brain — even when a PET scan is negative. The results were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Previously people would say one of the earliest events you would see is amyloid positivity in the brain on a PET scan,” said senior author David Vaillancourt, Ph.D., a professor and chair of the UF College of Health & Human Performance’s department of applied physiology and kinesiology. “Our findings suggest there seem to be events occurring both in the blood and in the brain before you detect amyloid positivity in the brain.”
Blood levels of amyloid were determined using Quest AD-Detect amyloid beta 42/40, a plasma blood test developed by Quest Diagnostics to help assess risk of Alzheimer’s pathology. Collaborators from UF, the University of Miami and Mount Sinai Medical Center in Miami Beach then analyzed diffusion MRI results showing the amount of free-water, or fluid unconstrained by brain tissue.
Two main mechanisms affect free-water: atrophy, which occurs when cells are dying, and inflammation, Vaillancourt said. The new study builds upon his lab’s discovery and validation of free-water imaging as a reliable, noninvasive biomarker for another neurodegenerative malady, Parkinson’s disease.

In the new study, participants who had positive blood tests for amyloid but negative PET scans for amyloid were shown to have brain changes on diffusion MRI, including decreased cortical volume and thickness, increased free-water in 24 outer and inner parts of the brain and decreased tissue microstructure in 66 total regions, as compared to those with a negative amyloid blood test and a negative amyloid PET scan, the researchers reported.
Currently, to assess patients for Alzheimer’s disease, physicians use a combination of medical history, neurological exams, cognitive and functional assessments, and additional tests that may include brain imaging, a spinal tap of cerebrospinal fluid and blood tests. Finding new methods and biomarkers to detect the disease earlier and at less expense could open the door to new clinical trials of experimental drugs to slow, prevent or treat the condition and help intervene sooner with currently available medications, Vaillancourt said.
The next step in this line of research to better correlate these findings, he said, is to follow the participants to see if those with positive amyloid blood tests become amyloid-positive on a PET scan as well as how free-water and blood change over time and how well these changes correlate with symptoms and cognitive testing and eventual clinical diagnosis of Alzheimer’s disease.
“We want to follow them over time to better understand the trajectory of change,” Vaillancourt said.

The development and progression of type 2 diabetes are affected by numerous biological processes, such as the body’s response to insulin, the health of insulin-producing pancreatic beta cells, and the functioning of metabolic pathways.
In a recent study published in Nature Medicine that analyzed individuals from diverse backgrounds, a team led by investigators at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard identified various genetic clusters involved in a broad range of biological mechanisms that may help explain ancestry-associated differences in type 2 diabetes clinical presentations.
“Type 2 diabetes is a disease of elevated blood sugar impacting approximately one in 10 people in the United States that can cause devastating health complications and is usually not cured. It is currently not fully understood why a given person develops the disease or why there is a lot of variation around clinical features across people with the disease,” says senior author Miriam S. Udler, MD, PhD, the director of the MGH Diabetes Genetics Clinic and an assistant professor of Medicine at Harvard Medical School.
Udler and her colleagues assessed genetic findings from more than 1.4 million individuals across various genetic ancestral backgrounds: African/African American, Admixed American, East Asian, European, South Asian, and multi-ancestry.
Analyses resulted in a final set of 650 genetic variants that had independent associations with type 2 diabetes and a final list of 110 diabetes-related clinical traits.
The scientists’ analyses validated diabetes-associated genetic clusters that they had identified in a previous study. (A genetic cluster is a group of two or more genetic regions that are suspected to share a generalized biological function).
The work also uncovered new genetic clusters related to decreased cholesterol levels, abnormal metabolism of bilirubin (which is created when the body breaks down hemoglobin from aged red blood cells, and abnormal lipid processing in fat and liver tissues).

In addition to identifying 12 genetic clusters and their biological functions that are associated with type 2 diabetes, the investigators found that the clusters helped to explain some of the dissimilarities in type 2 diabetes among different populations.
For example, it is well-documented that individuals from various self-identified non-white populations are more susceptible to type 2 diabetes at a given body mass index.
The study’s data suggest that this disparity is at least partially explained by variations in 2 of the clusters that the researchers identified that relate to how the body uses and stores fat — so that individuals with certain variants in these clusters (most often individuals from East Asian populations) face a higher risk of type 2 diabetes at lower body mass index levels than other individuals.
This discovery could help clinicians calculate an individual’s target body mass index level based on their genetic profile.
“Our study shows that the genetic underpinnings of type 2 diabetes can help explain clinical differences across populations,” says co-lead author Kirk Smith, MS, a computational biologist in MGH’s Center for Genomic Medicine. “Also, the genetic mechanisms of disease that we have identified offer the potential to guide development of curative therapies,” adds co-lead author Aaron J. Deutsch, MD, an instructor in the division of Endocrinology at MGH.
Additional authors include Carolyn McGrail, Hyunkyung Kim, Sarah Hsu, Alicia Huerta-Chagoya, Ravi Mandla, Philip H. Schroeder, Kenneth E. Westerman, Lukasz Szczerbinski, Timothy D. Majarian, Varinderpal Kaur, Alice Williamson, Noah Zaitlen, Melina Claussnitzer, Jose C. Florez, Alisa K. Manning, Josep M. Mercader, and Kyle J. Gaulton.
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Doris Duke Foundation, the American Diabetes Association, and the Novo Nordisk Foundation.

Pancreatic cancer has the highest mortality rate of all major cancers and is projected to become the second-leading cause of cancer-related deaths in the United States by 2030. It is especially difficult to treat because pancreatic tumors grow so quickly and are constantly evolving, making them prone to developing drug resistance.
Patient-derived organoids could change all that. In this emerging biotechnology, researchers obtain small tissue samples from patient biopsies and use them to grow three-dimensional cell cultures in the lab. These organoids act as miniature models of the patient’s pancreatic tumor, and can be used to test various drugs and evaluate which cancer treatments might work best.
The excitement over this tool’s clinical potential has led to an explosion of innovation in recent years. More than a dozen clinical trials of patient-derived organoids are currently in progress. However, the rush to get them into clinical trials has meant many experimental variables have yet to be fully vetted.
A recent study at the Salk Institute provides critical insights into the reliability and robustness of patient-derived organoids as a clinical model of pancreatic cancer. The findings, published January 9, 2024, in JCI Insight, reveal that organoids’ gene expression and drug responses are not affected by the brand of extracellular matrix used in the cell culture. However, one commercial product did increase the growth rate of pancreatic tumor organoids, making it particularly well-suited for the fast pace of pancreatic cancer treatment protocols.
“Everyone’s tumor is different, so we need personalized medicine to match a specific treatment to a specific tumor,” says senior author Dannielle Engle, an assistant professor and the Helen McLoraine Developmental Chair at Salk. “Instead of having to play this guessing game, patient-derived organoids offer clinicians a predictive model that helps them choose the right treatment from the beginning.”
As organoid biotechnology advances, the availability of commercial products to support this research has increased. Most organoids are grown in culture media, a liquid that supplies the cells with various nutrients they need to survive. In order to grow, the cells also need something to adhere to. In the human body, they’re surrounded by an extracellular matrix made of proteins and other molecules that provide a scaffold for the cells to grow on. In the lab, scientists obtain this matrix material from a variety of commercial sources. Depending on the duration of the trial or the status of the commercial supply chain, labs may have to use matrices from multiple commercial batches or even multiple brands to complete their experiments.
Several studies have recently shown that the type of liquid culture media that organoids are grown in can affect their phenotype, transcriptome, and drug response, meaning different cancer treatments might be recommended depending on which kind of culture media the organoid was grown in. Engle and her team set out to evaluate whether differences in extracellular matrices could have a similar effect.

“Whenever you’re developing a new clinical assay, you need to know how robust that assay is,” says Engle. “It needs to give you the same result whether you’re doing the test in a lab in California, Canada, or New York.”
First author Jan C. Lumibao, a postdoctoral researcher in Engle’s lab at the time of the study, tested the three most common brands of extracellular matrix: Matrigel, Cultrex, and UltiMatrix. Using a variety of research methods, he evaluated whether these different products had an effect on the organoids’ growth rate, gene expression, and drug response.
The findings showed that using different commercial matrices did not produce significant changes in the organoids’ gene expression patterns or drug responses, but did have some effect on the tissues’ growth rate.
“These matrices are biologically active, meaning there are real proteins and signaling molecules in them that could be interacting with the organoid, so the fact that we didn’t see significant differences in gene expression or drug response with the different brands of matrix was pleasantly surprising, and a big relief,” says Lumibao.
The researchers tested six different pancreatic cancer drugs — Gemcitabine, Abraxane,Oxaliplatin, Irinotecan, Fluorouracil, and Trametinib — and confirmed that using any one of the three commercial matrices would not have changed the clinical call for any patient.
However, one feature of the organoids was influenced by the brand of matrix. Pancreatic tumor organoids grew much faster in Matrigel compared to the other two types — which is a good thing. The faster the organoid grows, the sooner clinicians get the experimental results, and the earlier the patient can start treatment.

“In pancreatic cancer, timing is everything,” says Engle. “By the time you figure out that a drug isn’t working in the patient, it’s often too late to change their treatment plan. We want to sort this out as soon as possible, before the treatment has even begun.”
Engle says Cultrex and UltiMatrix are fine to use for organoid models and are unlikely to change experimental results, but the experiments will likely take 20-40% longer.
So why did different culture medias have such an effect on organoids, but different kinds of extracellular matrix did not? The researchers note that each lab’s culture media can include its own recipe of growth factors, whereas extracellular matrices tend to have the same array of growth factors, but at varying concentrations. These variations may be subtle enough to not have a dramatic effect on the organoids.
“Our findings provide further confidence that patient-derived organoids are an accurate and robust platform for evaluating patient drug response and informing clinical decisions,” says Engle. “Our teams at Salk are continuing to optimize organoid technology and confirm its utility in clinical settings, and we’re excited to see this impact patient outcomes in the future.”
Other authors include Shira R. Okhovat, Kristina L. Peck, Xiaoxue Lin, Kathryn Lande, and Shira Yomtoubian of Salk, and Isabella Ng, Hervé Tiriac, Andrew M. Lowy, and Jingjing Zou of UC San Diego.
The work was supported by the National Institutes of Health (R00CA024725, P30DK120515, T32CA009370, NIH-NCI CCSG: P30014195, NIH-NCI CCSG: P30014195, NIH-NCI CCSG: P30CA23100), the Pancreatic Cancer Action Network (19-20-ENGL), American Association for Cancer Research, the Lustgarten Foundation (21-20-67-ENGL), the University of California Tobacco-Related Disease Research Program (T31KT1898), Padres Pedal the Cause/C3 (#PTC2020), the Rose Hills Foundation, Mission Cure Capital LLC, the Mark Foundation for Cancer Research, the Emerald Foundation Inc., the Chapman Foundation, and the Helmsley Charitable Trust.

In a new study, participants’ levels of consumption of refined carbohydrates were statistically linked with their facial attractiveness as rated by heterosexual volunteers of the opposite sex. Visine and colleagues at the University of Montpellier, France, present these findings in the open-access journal PLOS ONE on March 6, 2024.
The Western diet consists of high levels of refined carbohydrates — foods processed in ways that typically remove much of their nutritional value, such as white flour, table sugar, and ingredients in many packaged snacks. Prior research has linked increased consumption of refined carbohydrates with adverse health effects, such as obesity, type II diabetes, and cardiovascular diseases. Preliminary evidence has suggested that consuming high levels of refined carbohydrates might also affect non-medical traits, such as a person’s attractiveness. To further explore this possibility, Visine and colleagues conducted a study involving 104 French male and female adults.
The researchers gave some of the participants a high-glycemic breakfast — one with refined carbohydrates known to boost blood sugar levels — while others received a low-glycemic breakfast. The participants also completed a questionnaire to evaluate their typical habits of consumption of refined carbohydrates. Additional heterosexual volunteers were then asked to rate the facial attractiveness of opposite-sex participants as captured in photos taken two hours after the provided breakfast. Only participants and volunteers with four grandparents of European origin were included in this research, to reduce cultural heterogeneity.
Statistical analysis showed that consuming the high-glycemic breakfast was associated with lower subsequent facial attractiveness ratings for both men and women. Chronic consumption of refined carbohydrates during breakfast and snacks was also associated with lower attractiveness ratings, although consumption of high-energy foods at these times was associated with higher attractiveness ratings.
The researchers noted some sex differences: for afternoon snacking in men specifically, high-energy intake was instead associated with lower attractiveness ratings, while high-glycemic intake was linked to higher attractiveness ratings.
All results held true after statistically accounting for other factors that could affect attractiveness, such as actual age, perceived age, BMI, smoking habits, and facial hairiness. Further research, including for larger and more diverse sample sizes, is needed to deepen understanding of exactly how refined carbohydrates may be linked to attractiveness and other social traits.
The authors add: “Facial attractiveness, an important factor of social interactions, seems to be impacted by immediate and chronic refined carbohydrate consumption in men and women.”

Males and females have differential physiological responses to COVID-19 infections, with males having larger increases in skin temperature, breathing rate and heart rate during an acute infection. That is the conclusion of a new study that used data from wearable devices and was published this week in the open-access journal PLOS ONE by Lorenz Risch of the Private University in the Principality of Liechtenstein and collaborators.
COVID-19 infections are known to impact physiological parameters including breathing rate, heart rate and skin temperature. A better understanding of sex-specific trajectories in these physiological changes could support the early detection and treatment of COVID-19
In the new study, (the COVI-GAPP study, www.covi-gapp.li), a member of the COVID-19 Remote Early Detection (COVID-RED) Consortium collected data on 1,163 people with the Ava wearable medical device. More than 1.5 million hours of physiological data were recorded and included in the new analysis. During the study period, spanning 2020 and 2021, 127 participants tested positive for COVID-19, of whom 82 had sufficient quality of data from the Ava app to include in the analysis.
The study found that, compared to females, males had larger increases in skin temperature, breathing rate and heart rate, and a larger decrease in heart rate variability during COVID-19 infection. Moreover, male participants’ breathing rate and heart rate remained at significantly higher levels during the recovery period as compared to their female peers. The study also tested potentially confounding variables, including BMI, age, hypertension, and alcohol and drug use, and found no impact of these variables on the associations between sex and physiology during infection. However, the study could not account for hormonal changes across the menstrual cycle among female participants.
The authors conclude that sex-specific biological responses to COVID-19 infection may be linked to the higher mortality and hospitalization rates observed in male COVID-19 patients. More work is needed to fully understand the biological underpinning of these sex differences.
The authors add: “The COVI-GAPP study has revealed significant sex-specific variations in vital parameter trends throughout the course of a SARS-CoV 2 infection. We firmly believe that utilizing wearable technology in research represents a valuable approach to gain deeper insights into diseases and their impacts, ultimately laying the groundwork not only for more timely and more accurate diagnoses but also for general advancements in precision medicine.”

Certain factors associated with developing age-related hearing loss differ by sex, including weight, smoking behavior, and hormone exposure, according to a study published on March 6, 2024 in the open-access journal PLOS ONE by Dong Woo Nam from Chungbuk National University Hospital, South Korea, and colleagues.
Age-related hearing loss (ARHL), slowly-advancing difficulty in hearing high-frequency sounds, makes spoken communication more challenging, often leading to loneliness and depression. Roughly 1 in 5 people around the world suffer from hearing loss, and this number is expected to rise as the global population ages. Since ARHL is irreversible, identifying it early and taking preventative measures are especially important. To better understand the factors associated with ARHL, and how the relative influence of these factors is shaped by sex, the researchers analyzed check-up health examination data from 2,349 participants aged over 60. After gathering each participant’s medical history and performing blood tests, a body composition test, and a basic hearing test, they ran statistical analyses to identify factors most strongly associated with ARHL risk for males and females.
The researchers found that while some factors — such as age — were associated with ARHL regardless of gender, others were differently associated with ARHL risk in males and females. For example, while being underweight showed a significant association with ARHL in males, both low weight and obesity showed significant associations in females. Smoking was associated with increased ARHL risk in males only, who were far more likely than females to identify as smokers in this sample population. Females who started menstruating at an earlier age were less likely to develop ARHL later in life, pointing towards a possible protective effect of the hormone estrogen.
This study does not allow elucidation of causal relationships between these factors and hearing loss, and further experimental studies will be necessary to confirm and better interpret these findings. However, the authors propose that assessing and counseling patients about their smoking behavior, weight, and menstruation may help improve screening and preventative treatment for ARHL.
The authors add: “Hearing loss should be prevented, even it is related to aging.”

An injectable hydrogel can mitigate damage to the right ventricle of the heart with chronic pressure overload, according to a new study published March 6 in Journal of the American College of Cardiology: Basic to Translational Science.
The study, by a research team from the University of California San Diego, Georgia Institute of Technology and Emory University, was conducted in rodents. In 2019, this same hydrogel was shown to be safe in humans through an FDA-approved Phase 1 trial in people who suffered a heart attack. As a result of the new preclinical study, the FDA approved an investigational new drug application for the Emory and Georgia Tech researchers to start a clinical trial with the hydrogel in pediatric patients in the coming months, once institutional approvals are received.
In this case, the injectable hydrogel is intended for children born with a condition that leaves them with an underdeveloped, nonfunctional left ventricle. The disorder, known as hypoplastic left heart syndrome, comprises less than 4 percent of congenital heart defects. But it is responsible for 40 percent of deaths associated with heart defects in newborns. Patients with the disorder have a 35 percent survival rate.
Current treatments consist of a series of three open heart surgeries all before the patient’s 5th year of life that reroutes oxygenated blood supply to the right ventricle. Pediatric patients who survive into childhood after surgery also receive medication and physical therapy, as well as a special diet. But this palliative surgery comes at a cost. In a healthy heart, the right ventricle’s job is to pump blood to the lungs; a job that entails dealing with blood at lower pressure and lower volume. When the right ventricle is forced to pump blood to the whole body, it develops several maladaptive traits, including overly large muscle and scarring. Eventually, the right ventricle begins to fail and patients will need a heart transplant.
“To the best of our knowledge, it’s the first time that an injectable biomaterial therapy has been evaluated to mitigate right ventricular heart failure,” said Jervaughn D. Hunter, the paper’s first author, who hails from Port Gibson, MS and earned his Ph.D. in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego.
In the rodent study, injecting the hydrogel into the right ventricle improved function and allowed the heart to tolerate increased blood pressure and volume. The treatment also slowed down the rate of tissue scarring and maladaptive muscle growth. The hope is that the hydrogel injection will increase the amount of time the patient’s heart functions.
“This isn’t a cure, but our goal is to prolong a patient’s life,” said Karen Christman, a bioengineering professor at UC San Diego and the paper’s corresponding author.

The treatment could also dramatically improve the patients’ quality of life, allowing better cognitive function and growth.
“They might be able to wait until they can get on an adult heart transplant list,” said Michael E. Davis, one of the paper’s senior authors and director of the Children’s Heart Research and Outcomes (HeRO) Center at Children’s Healthcare of Atlanta and Professor of Biomedical Engineering at the Georgia Institute of Technology and Emory University School of Medicine.
The hydrogel is made from cardiac extracellular matrix that is stripped of the cellular content through a cleansing process; dried and milled into powder form; and then liquefied into a fluid that can be easily injected into the heart. Once it hits body temperature and pH, the liquid turns into a semi-solid, porous gel that encourages the patient’s own cells to repopulate areas of damaged cardiac tissue and to improve heart function.
Positive results
Preclinically, the treament’s effects were first seen two weeks after injection.
Researchers in Christman’s lab prepared the hydrogel with tissue from both the right and left ventricles of the pig hearts. Interestingly, tissues on each side of the heart differ vastly.

Hydrogels from either side of the heart improved systolic function-the heart’s ability to pump blood. They also reduced heart muscle growth and scaring while prompting arteriole formation and growth. But overall, hydrogel derived from left-ventricle tissue was more effective. That’s likely because the hydrogel derived from right-ventricle tissue is richer in type 1 collagen, which may have led to the enhanced inflammatory response seen in the RV hydrogel treated group.
The injected hydrogel also affected gene expression, specifically pathways related to cardiac repair, including the development of the circulatory system, muscle structure and vasculature, as well as regulation of immune response and cellular response to oxygen-containing compounds.
Next, Children’s Healthcare of Atlanta, the children’s hospital collaborating with Georgia Tech and Emory will start recruiting for a clinical trial investigating the treatment’s efficacy in newborns with hypoplastic left heart syndrome.
Funding for the research came in part from the National Institutes of Health National Heart, Lung and Blood Institute.

The high-tech double-barrel nanopipette, developed by University of Leeds scientists, and applied to the global medical challenge of cancer, has — for the first time — enabled researchers to see how individual living cancer cells react to treatment and change over time — providing vital understanding that could help doctors develop more effective cancer medication.
The tool has two nanoscopic needles, meaning it can simultaneously inject and extract a sample from the same cell, expanding its potential uses. And the platform’s high level of semi-automation has sped up the process dramatically, enabling scientists to extract data from many more individual cells, with far greater accuracy and efficiency than previously possible, the study shows.
Currently, techniques for studying single cells usually destroy them, meaning a cell can be studied either before treatment, or after.
This device can take a “biopsy” of a living cell repeatedly during exposure to cancer treatment, sampling tiny extracts of its contents without killing it, enabling scientists to observe its reaction over time.
During the study, the multi-disciplinary team, featuring biologists and engineers, tested cancer cells’ resistance to chemotherapy and radiotherapy using glioblastoma (GBM) — the deadliest form of brain tumour — as a test case, because of its ability to adapt to treatment and survive.
Their findings are published March 6 in the journal Science Advances.
Significant breakthrough
One of the paper’s corresponding authors, Dr Lucy Stead, Associate Professor of Brain Cancer Biology in the University of Leeds’ School of Medicine, said: “This is a significant breakthrough. It is the first time that we have a technology where we can actually monitor the changes taking place after treatment, rather than just assume them.

“This type of technology is going to provide a layer of understanding that we have simply never had before. And that new understanding and insight will lead to new weapons in our armoury against all types of cancer.”
She added: “GBM is the cancer in most need of those new weapons because in 20 years there has been no improvement in survival in this disease.
“It is lagging behind so much and we think that is because of the highly ‘plastic’ nature of these tumours — their ability to adapt to treatment and survive it.
“That is why it is so important that we can dynamically observe and characterise these cells as they change, so we can map out the journey these cells can take, and subsequently find ways to stop them at every turn. We simply couldn’t do that with the technologies that we had.”
Transformative
Dr Stead leads the Glioma Genomics research group at the Leeds Institute of Medical Research at St James’s Hospital, which is focused on trying to cure GBM brain tumours. She added: “This technology could be transformative for this particular cancer, helping us finally identify effective treatments for this awful, incurable disease.”
The research was primarily funded by The Brain Tumour Charity, which counts former Leeds footballer Dominic Matteo as one of its high-profile supporters. Matteo did not have GBM but underwent surgery to remove a brain tumour in 2019.

Dr Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, said: “We know glioblastoma cells respond differently to treatment, often developing treatment resistance which leads to recurrence. The development of this novel technology, which can extract samples from tumour cells grown in the lab before and after treatment, will give a unique insight into how drug resistance may develop and lead to tumours growing back.
“We hope that this important work, funded by The Brain Tumour Charity, will improve our knowledge of these complex brain tumours and allow us to find new, more effective treatments — something so urgently needed for those faced with this devastating disease.”
Collaborative
The study was a collaboration between researchers from Leeds’ Bragg Centre for Materials Research; Leeds’ School of Electronic and Electrical Engineering; Leeds Institute of Medical Research, and the Earlham Institute, Norwich, who studied single GBM cells over a period of 72hrs.
They used the nanosurgical platform, which is far too small to be manipulated by hand. The miniscule needles are precisely controlled by robotic software to manoeuvre them into position, into the cells in the petri dish. The nanopipette’s second needle plays a fundamental role in controlling the equipment.
The device allows scientists to take samples repeatedly, to study the progression of disease in an individual cell. Much research on molecular biology is carried out on populations of cells, giving an average result that ignores the fact that every cell is different.
Some cells die during treatment, but others survive. The key to finding a cure is understanding what allows one cell to survive and what is happening to the ones that die.
Unprecedented precision
Lead author Dr Fabio Marcuccio, Research Associate in the Faculty of Medicine at Imperial College London, who carried out the research while at Leeds, said: “Our device allows the study of the way brain cancer cells adapt to treatment over time, with unprecedented precision. This tool will provide data that could lead to significant improvements in cancer treatment and prognoses.”
He added: “This work is the result of a collaborative effort with my colleagues and co-leads Dr Chalmers Chau, Research Fellow in Bionanotechnology in Leeds’ School of Electronic and Electrical Engineering, and Dr Georgette Tanner, formerly of Leeds, now Bioinformatician at Oxford Nanopore Technologies, whose contributions were fundamental to the experimental design and data analysis. This demonstrates the importance of creating an interdisciplinary team to tackle the biggest challenges of our time.”
Cancer cell plasticity — the ability of cells to change their behaviours — is one of the biggest challenges in cancer treatment as it remains poorly understood. GBM cancer cells are particularly “plastic”: they can adapt very quickly, and this is thought to help them develop resistance to radiotherapy and chemotherapy. Learning how these cells adapt, and subsequently how we can block them, could prevent cancer from recurring, something which almost always happens with GBM.
Camilla Hawkins, an occupational therapist from London, was diagnosed with GBM in August 2022. The 55-year-old said: “Any findings, such as these, that could help inform new treatments, has got to be welcomed. Extended good quality of life is worth living, even where the prognosis is terminal.”
Crucially important
The other corresponding author and co-lead Dr Paolo Actis, Associate Professor of Bio-Nanotechnology in Leeds’ School of Electronic and Electrical Engineering, has been working on the nanobiopsy tool for around 15 years and said its new capabilities, compared to its original scope, provided “remarkable advantages.”
He added: “Cancer cells that are not killed by chemotherapy are the ones that make the cancer grow back and lead to death.
“Our tool can pinpoint these cells and we can now perform biopsies on them so we can specifically study how the ones that survive treatment have changed.
“This is crucially important as the more we can understand how the cells change, the more drugs we can develop to stop them from adapting.”
Dr Stead said further research needed to be carried out, using this technology on many more samples in the lab and in humans, but that it had already yielded hugely valuable information.
Additional funding was provided by UK Research and Innovation and the European Commission.

Artificial intelligence helped clinicians to accelerate the design of diabetes prevention software, a new study finds.
Publishing online March 6 in the Journal of Medical Internet Research, the study examined the capabilities of a form of artificial intelligence (AI) called generative AI or GenAI, which predicts likely options for the next word in any sentence based on how billions of people used words in context on the internet. A side effect of this next-word prediction is that the generative AI “chatbots” like chatGPT can generate replies to questions in realistic language, and produce clear summaries of complex texts.
Led by researchers at NYU Langone Health, the current paper explores the application of ChatGPT to the design of a software program that uses text messages to counter diabetes by encouraging patients to eat healthier and get exercise. The team tested whether AI-enabled interchanges between doctors and software engineers could hasten the development of such a personalized automatic messaging system (PAMS).
In the current study, eleven evaluators in fields ranging from medicine to computer science successfully used ChatGPT to produce a version of the diabetes tool over 40 hours, where an original, non-AI-enabled effort had required more than 200 programmer hours.
“We found that ChatGPT improves communications between technical and non-technical team members to hasten the design of computational solutions to medical problems,” says study corresponding author Danissa Rodriguez, PhD, assistant professor in the Department of Population Health at NYU Langone, and member of its Healthcare Innovation Bridging Research, Informatics and Design (HiBRID) Lab. “The chatbot drove rapid progress throughout the software development life cycle, from capturing original ideas, to deciding which features to include, to generating the computer code. If this proves to be effective at scale it could revolutionize healthcare software design.”
AI as Translator
Generative AI tools are sensitive, say the study authors, and asking a question of the tool in two subtly different ways may yield divergent answers. The skill required to frame the questions asked of chatbots in a way that elicits the desired response, called prompt engineering, combines intuition and experimentation. Physicians and nurses, with their understanding of nuanced medical contexts, are well positioned to engineer strategic prompts that improve communications with engineers, and without learning to write computer code.
These design efforts, however, where care providers, the would-be users of a new software, seek to advise engineers about what it must include can be compromised by attempts to converse using “different” technical languages. In the current study, the clinical members of the team were able to type their ideas in plain English, enter them into chatGPT, and ask the tool to convert their input into the kind of language required to guide coding work by the team’s software engineers. AI could take software design only so far before human software developers were needed for final code generation, but the overall process was greatly accelerated, say the authors.
“Our study found that chatGPT can democratize the design of healthcare software by enabling doctors and nurses to drive its creation,” says senior study author Devin Mann, MD, director of the HiBRID Lab, and strategic director of Digital Health Innovation within NYU Langone Medical Center Information Technology (MCIT).”GenAI-assisted development promises to deliver computational tools that are usable, reliable, and in-line with the highest coding standards.”
Along with Rodriguez and Mann, study authors from the Department of Population Health at NYU Langone were Katharine Lawrence, MD, Beatrix Brandfield-Harvey, Lynn Xu, Sumaiya Tasneem, and Defne Levine. Javier Gonzalez,technical lead in the HIBRID Lab, was also a study author. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant 1R18DK118545-01A1.

Here’s what to know about the legislation, which the state legislature is expected to approve overwhelmingly on Wednesday.The Alabama legislature on Wednesday is expected to pass legislation that will make it possible for fertility clinics in the state to reopen without the specter of crippling lawsuits.But the measure, hastily written and expected to pass by a huge bipartisan margin, does not address the legal question that led to clinic closings and set off a stormy, politically fraught national debate: Whether embryos that have been frozen and stored for possible future implantation have the legal status of human beings.The Alabama Supreme Court made such a finding last month, in the context of a claim against a Mobile clinic brought by three couples whose frozen embryos were inadvertently destroyed. The court ruled that, under Alabama law, those embryos should be regarded as people, and that the couples were entitled to punitive damages for the wrongful death of a child.Legal experts said the bill, which Governor Kay Ivey has signaled she will sign, would be the first in the country to create a legal moat around embryos, blocking lawsuits or prosecutions if they are damaged or destroyed.But though the measure is likely to bring enormous relief to infertility patients whose treatments had been abruptly suspended, it will do so in exchange for limiting their ability to sue when mishaps to embryos do occur. Such constraints in a field of medicine with limited regulatory oversight could make the new law vulnerable to court challenges, the experts said.Here are answers to some key questions:What does the measure do?It creates two tiers of legal immunity. If embryos are damaged or destroyed, direct providers of fertility services, including doctors and clinics, cannot be sued or prosecuted.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.