Publisher Health

A new artificial intelligence tool that interprets medical images with unprecedented clarity does so in a way that could allow time-strapped clinicians to dedicate their attention to critical aspects of disease diagnosis and image interpretation.
The tool, called iStar (Inferring Super-Resolution Tissue Architecture), was developed by researchers at the Perelman School of Medicine at the University of Pennsylvania, who believe they can help clinicians diagnose and better treat cancers that might otherwise go undetected. The imaging technique provides both highly detailed views of individual cells and a broader look of the full spectrum of how people’s genes operate, which would allow doctors and researchers to see cancer cells that might otherwise have been virtually invisible. This tool can be used to determine whether safe margins were achieved through cancer surgeries and automatically provide annotation for microscopic images, paving the way for molecular disease diagnosis at that level.
A paper on the method, led by Daiwei “David” Zhang, PhD, a research associate, and Mingyao Li, PhD, a professor of Biostatistics and Digital Pathology, was published today in Nature Biotechnology.
Li said that iStar has the ability to automatically detect critical anti-tumor immune formations called “tertiary lymphoid structures,” whose presence correlates with a patient’s likely survival and favorable response to immunotherapy, which is often given for cancer and requires high precision in patient selection. This means, Li said, that iStar could be a powerful tool for determining which patients would benefit most from immunotherapy.
The development of iStar was taken on as part of the field of spatial transcriptomics, a relatively new field used to map gene activities within the space of tissues. Li and her colleagues adapted a machine learning tool called the Hierarchical Vision Transformer and trained it on standard tissue images. It begins by breaking down images into different stages, starting small and looking for fine details, then moving up and “grasping broader tissue patterns,” according to Li. A network guided by the AI system within iStar uses the information from the Hierarchical Vision Transformer to then absorb all of that information and apply it to predict gene activities, often at near-single-cell resolution.
“The power of iStar stems from its advanced techniques, which mirror, in reverse, how a pathologist would study a tissue sample,” Li explained. “Just as a pathologist identifies broader regions and then zooms in on detailed cellular structures, iStar can capture the overarching tissue structures and also focus on the minutiae in a tissue image.”
To test the efficacy of the tool, Li and her colleagues evaluated iStar on many different types of cancer tissue, including breast, prostate, kidney, and colorectal cancers, mixed with healthy tissues. Within these tests, iStar was able to automatically detect tumor and cancer cells that were hard to identify just by eye. Clinicians in the future may be able to pick up and diagnose more hard-to-see or hard-to-identify cancers with iStar acting as a layer of support.

In addition to the clinical possibilities presented by the iStar technique, the tool moves extremely quickly compared to other, similar AI tools. For example, when set up with the breast cancer dataset the team used, iStar finished its analysis in just nine minutes. By contrast, the best competitor AI tool took more than 32 hours to come up with a similar analysis.
That means iStar was 213 times faster.
“The implication is that iStar can be applied to a large number of samples, which is critical in large-scale biomedical studies,” Li said. “Its speed is also important for its current extensions in 3D and biobank sample prediction. In the 3D context, a tissue block may involve hundreds to thousands of serially cut tissue slices. The speed of iStar makes it possible to reconstruct this huge amount of spatial data within a short period of time.”
And the same goes for biobanks, which store thousands, if not millions, of samples. This is where Li and her colleagues are next aiming their research and extension of iStar. They hope to help researchers gain better understandings of the microenvironments within tissues, which could provide more data for diagnostic and treatment purposes moving forward.
This research was funded by the National Institutes of Health (R01GM125301 and R01HG013185).

Identifying new ways to target proteins involved in human diseases is a priority for many researchers around the world. However, discovering how to alter the function of these proteins can be difficult, especially in live cells. Now, scientists from Scripps Research have developed a new method to examine how proteins interact with drug-like small molecules in human cells — revealing critical information about how to potentially target them therapeutically.
The strategy, published in Nature Chemical Biology on January 2, 2024, uses a combination of chemistry and analytical techniques to reveal the specific places where proteins and small molecules bind together. Ultimately, this method could lead to the development of more targeted and effective therapeutics.
“Our new technology could be used to find new druggable sites on proteins for any human disease, from cancer to Alzheimer’s disease,” says associate professor, Department of Chemistry Christopher Parker, PhD, senior author of the study. “We’re unrestricted in how this could be used. Our work has the potential to usher in a whole new way of drug discovery.”
The Parker lab aims to discover how proteins function in every human cell type to develop effective therapeutics for a wide range of human diseases. In this study, Parker and his team built off his initial work in the lab of Scripps Research professor Benjamin Cravatt to create a new method of examining how proteins interact with small molecules in living cells. They developed an analytical strategy to better understand how these proteins engage with small molecules at much higher resolution than ever before. To do this, they used chemical probes called photoaffinity probes, which are molecules that can be activated by light to allow the probes to capture a bound protein.
By gathering data from the interactions of proteins with photoaffinity probes, the Parker team identified locations on proteins where small molecules could connect and bind. Essentially, the team found over a thousand new locks (binding sites on the proteins) and corresponding keys (small molecules), the vast majority of which were new places of small-molecule binding that had not been reported before. Additionally, they found new features of the binding sites-such as new shapes.
“Identifying these specific binding sites will help scientists design new molecules that fit these pockets even better, potentially leading to more effective therapeutics,” says Jacob M. Wozniak, co-first author, and former postdoctoral fellow in the Parker lab. The other co-first author of the paper was Weichao Li, PhD, a research associate also in the Parker lab.
Using the wealth of data in this study and collaborating with co-author Stefano Forli, PhD, associate professor in the Department of Integrative Structural and Computational Biology, the authors then modeled how certain molecules might bind to these proteins. This library of information could be used to design therapeutics that interact with proteins in a more targeted way.
“Our new process reveals additional opportunities for therapeutic intervention and discovery in human cells,” says Parker. “Next, we plan to use this technology to target proteins relevant for autoimmune diseases and cancer.”

St. Jude Children’s Research Hospital scientists found that cytonemes (thin, long, hair-like projections on cells) are important during neural development. Cytonemes connect cells communicating across vast distances but are difficult to capture with microscopy in developing vertebrate tissues. The researchers are the first to find a way to visualize how cytonemes transport signaling molecules during mammalian nervous system development. The findings were published in Cell.
“We showed cytonemes are a direct express route for signal transport,” said corresponding author Stacey Ogden, PhD, St. Jude Department of Cell and Molecular Biology. “Cells need to communicate with each other during development and tissue homeostasis and be able to reach more than just their neighbors. We’ve identified one way that signals are loaded into cytonemes for transport to responding cell populations and demonstrated that tissue patterning does not happen properly when this mode of signal dispersion is compromised.”
Express signal delivery sets up the nervous system for success
Researchers in Ogden’s lab were the first to visualize mammalian cytonemes in the developing nervous system by combining modern microscopy techniques with optimized sample preparations.
“For a long time, visualizing these structures in developing mammalian tissue has been challenging,” Ogden said. “But we’ve finally found a way.”
Using their new methods, the scientists captured images of how cytonemes act as an “express” system that can skip over intervening cells to directly deliver signals to more distant ones, similar to an express subway that only stops at major stations. One of the major stations is the notochord, which produces a signal that plays a crucial role in organizing the developing spinal cord. Ogden’s team captured images of the transport process happening in the cytonemes originating from the notochord.
When the researchers prevented signaling proteins from entering cytonemes, neural development was disrupted in mouse models, causing major neurological defects.

“This is the first demonstration of these cytoneme-based transport processes occurring during the development of a complex mammalian tissue such as the neural tube,” Ogden said. “Then we showed that when we reduce cytoneme numbers or decrease the ability of cells to load signaling proteins into these structures, we get developmental defects.”
Cytoneme transport helps establish the gradient
Mammalian development is a carefully guided process that must be coordinated for all organs and tissues to form correctly. One way cells know when to adopt a specific fate is by responding to distinct thresholds of signaling proteins called morphogens. Cells will respond differently to these signals across a signaling gradient, taking on different characteristics in response to high and low concentrations of a particular morphogen. A good gradient is necessary for development; a bad gradient can spell disaster.
Despite their importance, how these patterns of morphogens are created across fields of organizing cells has remained a mystery. Simple diffusion can explain some, but not all, of these gradients. The neurological deficits created when the scientists blocked signals from entering cytonemes provide evidence that supports a key role for cytoneme signaling during morphogen patterning.
“These deficits are really the first direct evidence that cytoneme-based signaling plays a key role during neural tube patterning,” Ogden said.
Transporting ‘sonic hedgehog’ through cytonemes
The St. Jude group clarified one way that a gradient of the sonic hedgehog morphogen is formed in the neural tube. Sonic hedgehog was already known as a critical signaling molecule in neural development, but its route to reach its target cells has been difficult to ascertain. The study identified cytonemes as key contributors to a solution that creates the sonic hedgehog signaling gradient. Correspondingly, when sonic hedgehog could not be loaded in cytonemes, its signaling function was compromised.

“In the morphogen signaling research field, we’ve always wanted to know how a signal gets from one population of cells to spread across a receiving cell population to make a gradient,” Odgen said. “It’s really exciting to show that cells that are producing morphogen signals are playing an active role in getting them to where they need to go through cytonemes. The signaling cell is not only making the morphogen, but it’s also helping to physically deliver the signal.”
What remains unclear is how widespread cytoneme express transport of signaling proteins is in development.
“Here, we’ve used sonic hedgehog as a model,” Ogden said. “But we also have evidence that these structures may be important for transporting other signals that are crucial during neural tube development. Now that we’ve developed a system to visualize these cytonemes, we can begin to uncover the true breadth of their function.”

New research has identified the specific biological mechanism behind the muscle dysfunction found in myotonic dystrophy type 1 (DM1) and further shows that calcium channel blockers can reverse these symptoms in animal models of the disease. The researchers believe this class of drugs, widely used to treat a number of cardiovascular diseases, hold promise as a future treatment for DM1.
“The main finding of our study is that combined calcium and chloride channelopathy is highly deleterious and plays a central role in the function impairment of muscle found in the disease,” said John Lueck, Ph.D., an assistant professor at the University of Rochester Medical Center (URMC) in the Departments of Pharmacology and Physiology, and Neurology. “Our research also suggests that muscle impairment in DM1 is potentially mitigated by common clinically available calcium channel blockers and that calcium channel modulation is a potential therapeutic strategy.” Lueck is lead author of the study, which appears in the Journal of Clinical Investigation.
Toxic RNA disrupts muscle function
Myotonic dystrophy is one of the most common forms of muscular dystrophy. People with the disease have muscle weakness and prolonged muscle tensing (myotonia), making it difficult to relax muscles after use. The disease also affects the eyes, heart, and brain, leading eventually to difficulty walking, swallowing, and breathing.
More than 20 years ago, URMC neurologist Charles Thornton, MD, and others uncovered how a genetic flaw-a ‘stutter’ that results in thousands of repetitions of code on a segment of chromosome 19-gives rise to DM1. This repeat expansion, which grows longer over time, results in the creation of abnormal RNA which accumulates in the nucleus of cells and affects the normal processing of many other RNAs. Thornton is a co-author of the current study and the research was a collaboration between the Lueck and Thornton labs.
This toxic RNA specifically disrupts the function of muscleblind-like (MBNL) proteins responsible for regulating the splicing of transcripts important for maintaining healthy muscle function. Among other things, these splicing defects impair the function of receptors for calcium and chloride channels, gateways in muscle cells that help convert electrical signals from motor neurons into chemical signals within the muscle cells. Specifically, the release of stored calcium causes muscle cells to contract, a process called excitation-contraction coupling (ECC), while lowering the concentration of the chemical depolarizes the cell and allows it to relax.
Calcium channel blockers to the rescue
Lueck and his colleagues were particularly interested in understanding this cycle as it held the potential to explain the muscular dysfunction in DM1. The first challenge was to focus on the muscle impact of the disease and eliminate the “noise” of the dozens of other defects wrought by the toxic RNA. “Myotonic dystrophy is a really complicated disorder, which you can think of as almost like an aggregate of many diseases,” said Lueck. To accomplish this, the team created a mouse model that mimicked four of the splicing defects found in DM1 in genes associated with the calcium and chloride channels. These mice exhibited severe myotonia, muscle weakness, impaired mobility, respiratory defects, and a marked reduction in lifespan.

The involvement of the calcium channel in muscle dysfunction presented an opportunity and a target — calcium channel blockers are widely used to treat, among other things, high blood pressure, cardiac arrhythmias, and migraines. When the team treated the mice with verapamil, a calcium channel blocker used to treat hypertension and chest pains, the mice quickly recovered muscle function and began to resemble their healthy, wild type peers. The findings were possible by years of close observation of the animals by Lily Cisco, a graduate student in the Lueck lab who is first author of the study.
The researchers are quick to emphasize that verapamil is NOT an appropriate treatment for DM1 in humans due to its potential cardiac side effects. “We think that the calcium channel is a new therapeutic target and if we can target it correctly, pharmacologically that it will improve muscle function and health. Our goal now is to find the appropriate and safe calcium channel blocker that will do the job and we believe it exists.”
Additional co-authors include Matthew Sipple, and Katherine Edwards with URMC. The research was supported with funding from the National Institute of General Medical Sciences, the National Center for Advancing Translational Sciences, the National Institute of Neurological Disorders and Stroke, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Myotonic Dystrophy Foundation.

Aptamers, nucleic acids1 capable of selectively binding to viruses, proteins, ions, small molecules, and various other targets, are garnering attention in drug development as potential antibody substitutes for their thermal and chemical stability as well as ability to inhibit specific enzymes or target proteins through three-dimensional binding. They also hold promise for swift diagnoses of colon cancer and other challenging diseases by targeting elusive biomarkers.2 Despite their utility, these aptamers are susceptible to easy degradation by multiple enzymes, presenting a significant challenge.
Professor Seung Soo Oh and his team from the Department of Materials Science and Engineering at Pohang University of Science and Technology (POSTECH), including Dr. Byunghwa Kang, and Dr. Soyeon V Park, have introduced a breakthrough approach using ionic liquids to address the challenges in functional nucleic acid research, paving the way for diverse applied research. Their findings have been published in Nucleic Acids Research.
Functional nucleic acids are termed as such for their versatility in not only storing and transmitting genetic information in living organisms but also in performing varied functions, such as detecting target molecules or catalyzing biochemical reactions similar to aptamers. However, these nucleic acids face obstacles in research applications due to vulnerability to degradation by hydrolases.3 Conventional preservation methods such as ultra-low-temperature cryogenic storage or chemical modification of nucleic acids fail to inhibit a wide array of enzymes, resulting in significant impairment of the nucleic acids’ useful functions.
The team shifted away from the conventional belief that “water is essential.” Although nucleic acids serve various roles and exhibit multiple functions in water, enzymes that break them down remain active in this medium. Hence, water acts as both the “home” and the “graveyard” for nucleic acids. The research team marked a significant milestone by globally validating the capability of nucleic acids to retain multiple functions in a choline dihydrogen phosphate-based ionic liquid. This ionic liquid, also present in our bodies, exhibits exceptional biocompatibility. The choline cation within the liquid effectively shields the negative charge of nucleic acids, preventing their contact with water and thereby fundamentally impeding hydrolysis.
In experiments, this liquid created an environment where nucleic acids resisted degradation regardless of the enzyme type, extending their half-life up to 6.5 million times. Even in extreme environments with a mix of seven different hydrolases, the nucleic acids remained completely intact and functional.
Furthermore, the team applied this innovation to enable aptamer-based biomolecular diagnostics within biological solutions for the first time. Previously, saliva containing numerous nucleic acid hydrolases made it impossible to use functional nucleic acids for biomarker detection. However, the team shielded the aptamers with an ionic liquid added to the saliva sample to achieve simple molecular diagnostics.
Professor Seung Soo Oh emphasized, “By demonstrating that nucleic acids can maintain functionality even in unexplored or contaminated samples and body fluids, we’ve demonstrated their limitless application potential.” Dr. Byunghwa Kang expressed hope, stating, “This research will significantly benefit the application of not only nucleic acids but also other molecules susceptible to hydrolysis.”
This research was conducted with support from various institutions, including grants from the National Research Foundation of Korea funded by the Ministry of Science and ICT, the Korea Evaluation Institute of Industrial Technology, the Institute of Civil Military Technology Cooperation funded by the Defense Acquisition Program Administration and the Ministry of Trade, Industry & Energy, the Korea Basic Science Institute, and the Brain Korea 21 FOUR project.

1. Nucleic acids Polymers composed of units called nucleotides. These are two types: DNA and RNA.
2. Biomarker An indicator that can objectively measure the normal or pathological state of an organism, the degree of response to a drug, etc., using proteins, DNA, RNA, metabolites, etc.
3. Hydrolase An enzyme that catalyzes a reaction that breaks down chemical bonds using water

Just like a doctor adjusts the dose of a medication to the patient’s needs, the expression of therapeutic genes, those modified in a person to treat or cure a disease via gene therapy, also needs to be maintained within a therapeutic window. Staying within the therapeutic window is important as too much of the protein could be toxic, and too little could result in a small or no therapeutic effect.
Although the principle of therapeutic window has been known for a long time, there has been no strategy to implement it safely, limiting the potential applications of gene therapy in the clinic. In their current study published in the journal Nature Biotechnology, researchers at Baylor College of Medicine report on a technology to effectively regulate gene expression, a promising solution to fill this gap in gene therapy clinical applications.
“Although there are several gene regulation systems used in mammalian cells, none has been approved by the U.S. Food and Drug Administration for clinical applications, mainly because those systems use a regulatory protein that is foreign to the human body, which triggers an immune response against it,” said corresponding author Dr. Laising Yen, associate professor of pathology and immunology and of molecular and cellular biology at Baylor. “This means that the cells that are expressing the therapeutic protein would be attacked, eliminated or neutralized by the patient’s immune system, making the therapy ineffective.”
For more than a decade, Yen and his colleagues have been working on this technology and now they have found a solution to overcome the main obstacles in its clinical use. “The solution we found does not involve a foreign regulatory protein that will evoke an immune response in patients. Instead, we use small molecules to interact with RNA, which typically do not trigger an immune response,” Yen said. “Other groups also have made attempts to resolve this critical issue, but the drug concentrations they used are beyond what the FDA has approved for patients. We were able to engineer our system in such a way that it works at the FDA-approved dosage.”
A switch to turn genes on/off on cue
Yen and his colleagues developed a system that turns genes on to different levels on cue using small molecules at FDA-approved doses. The switch is placed in the RNA, the copy of genetic material that is translated into a protein. This approach allows the researchers to control the protein’s production a step back by controlling its RNA.
The RNA of interest is first engineered to contain an extra polyA signal, akin to a “stop sign” that genes naturally use to mark the end of a gene. When the machinery of the cell detects a polyA signal in the RNA, it automatically makes a cut and defines the cut point as the end of the RNA. “In our system, we use the added polyA signal, not at the end, but at the beginning of the RNA, so the cut destroys the RNA and therefore the default is no protein production. It is turned off until we turn it on with the small molecule,” Yen said.

To turn on the gene at the desired level, the team engineered a switch on the RNA. They modified a section of the RNA near the polyA signal such that it can now bind to a small molecule, FDA-approved tetracycline in this case. “When tetracycline binds to that section that functions as a sensor on the RNA, it masks off the polyA signal, and the RNA will now be translated into protein,” Yen said.
Imagine the now possible future situation. A patient has received gene therapy that provides a gene to compensate for a malfunctioning gene that causes a medical condition. The gene the patient received has the switch, which allows the physician to control the production of the therapeutic protein. If the patient only requires a small amount of the therapeutic protein, then he/she will only take a small dose of tetracycline, which will turn on the therapeutic gene only a little. If the patient needs more therapeutic protein, then he/she would take more tetracycline to boost production. To stop production of the therapeutic protein, the patient stops taking tetracycline. In the absence of tetracycline, the switch will be back to its default off position. Some diseases may benefit from the presence of constant low levels of therapeutic protein. In that case, the technology has the flexibility to pre-adjust the default level to specified levels of protein expression while retaining the option of dialing up the expression with tetracycline.
“This strategy allows us to be more precise in the control of gene expression of a therapeutic protein. It enables us to adjust its production according to disease’s stages or tune to the patients’ specific needs, all using the FDA-approved tetracycline dose,” Yen said. “Our approach is not disease-specific, it can theoretically be used for regulating the expression of any protein, and potentially has many therapeutic applications. In addition, this system is more compact and easier to implement than the existing technologies. Therefore, it also can be very useful in the lab to turn a gene of interest on or off to study its function.”
Liming Luo, Jocelyn Duen-Ya Jea, Yan Wang and Pei-Wen Chao, all at Baylor College of Medicine, also contributed to this work.
This work was supported by an E&M Foundation Pre-Doctoral Fellowship for Biomedical Research, NIH grants (R01EB013584, UM1HG006348, R01DK114356, R01HL130249, P30 CA125123 and S10 RR024574), Biogen SRA, seed fund from Department of Pathology and Immunology at Baylor College of Medicine and CPRIT Core Facility Support Award CPRIT-RP180672.

Farmers in sub-Saharan Africa need to diversify away from growing maize and switch to crops that are resilient to climate change and supply key micronutrients for the population, say researchers.
Maize is a staple crop across the region where it is grown and consumed in vast quantities. 
Led by Dr Stewart Jennings from the University of Leeds, the study argues that diversification towards fruits, vegetables and crops such as cassava, millet and sorghum will improve nutrition security in the country, with people getting sufficient micronutrients essential for good health.
The study also says the quantity of food produced must increase — and unless yields are boosted to an unprecedented level, more land will have to be brought into agricultural production.
Sub-Saharan Africa is home to around 1.2 billion people, and according to figures from the World Bank, the population will grow by an additional 740 million people by 2050. 
Farmers will have to boost the amount of food grown at a time when climate change will result in increasingly extreme conditions, affecting what crops can be grown.
The researchers say the population is at risk of “food and nutrition insecurity” unless effective ways of adapting to climate change are identified. Integral to any decisions is a requirement that crops need to be nutritious and provide sufficient energy for the population. 
Professor Jennie Macdiarmid, from the Rowett Institute at the University of Aberdeen and one of the authors of the paper, said: “The study has highlighted the need to place nutrition at the heart of agricultural policy to avoid the long-term unintended consequence of failing to produce food that can deliver the nutritional needs of the population.

“If policy solutions focus only on increasing production of calories and adapting to be climate smart, it is likely there will be negative consequences for health through nutritionally poor diets.”
The study — Stakeholder-driven transformative adaptation is needed for climate-smart nutrition security in sub-Saharan Africa - is published in the scientific journal Nature Food. 
More than 50 researchers contributed to the investigation, which involved talking to policymakers and other stakeholders in the food and agriculture sectors in four countries in sub-Saharan Africa: Malawi, South Africa, Tanzania and Zambia.
‘Agriculture and nutrition policies can sit in siloes’
The researchers used the iFEED assessment framework to investigate policy options to create an agricultural system that is resilient to climate change and would supply enough nutritionally-adequate food to meet the food and nutritional needs of the population.
“Too often food, agriculture and nutrition policies sit in siloes across different government departments,” said Dr Jennings, a Research Fellow in the School of Earth and Environment at the University of Leeds. 
“This study provides holistic evidence that combines information on environmental impacts of food system changes and the changes needed for population level nutrition security. The research shows that action can be taken to adapt to climate change and improve nutrition security in sub-Saharan Africa.” 

Stakeholders in each country identified key uncertainties in the future of the food system. iFEED explores these uncertain futures and identifies key policy issues that decision makers working in the agriculture and food sectors need to consider. 
The scientists say there needs to be a fundamental shift - or ”transformative approach” - in agriculture to incorporate nutritional needs. 
Diversifying into soybean production is one option. Soybean crops are more likely to withstand the impacts of climate change compared to maize. Dr Ndashe Kapulu, from the Zambia Agriculture Research Institute and contributing author to the study has been involved in studies to assess how soybean could improve the income of commercial and small-scale farmers.
He said: “Many countries in sub-Saharan Africa will be better able to handle climate change and other stresses if they have more diverse food systems, such as the transition to soybean production in Zambia.
“As scientists, we need to generate enough evidence in our research to help make changes that support and guide actions to make the agrifood system more resilient.”
Increasing the production and consumption of animal-based products in sub-Saharan Africa could also improve nutritional quality of diets but the scientists warn that it should not reach the unsustainable production levels seen in some higher income countries. 
More animal-based products would cause a rise in greenhouse gas emissions, although the researchers say that this could be tolerable given sub-Saharan Africa’s need to reduce the risk of nutritionally-inadequate diets — and that its greenhouse gas emissions are relatively low.
The study involved researchers from a number of organisation including the University of Leeds, University of Aberdeen, the Met Office, Chatham House and FANRPAN.
iFEED is a database - developed in part by the University of Leeds under the GCRF AFRICAP programme and the CGIAR Initiative on Climate Resilience — to help decision makers deliver food system policies which are resilient to climate change and deliver nutritious food — reducing the risk of food and nutrition insecurity. 

Could healthy fats found in nuts and fish slow the progression of potentially deadly lung scarring known as pulmonary fibrosis and delay the need for lung transplants?
UVA pulmonary researchers looked at the association between blood-plasma levels of omega-3 fatty acids — the heart-healthy fats found in foods such as salmon and flaxseeds — and the progression of pulmonary fibrosis, as well as how long patients could go without needing a transplant. The researchers found that higher levels of omega-3 were associated with better lung function and longer transplant-free survival.
While more research is needed, the researchers say their findings warrant clinical trials to determine if interventions that raise omega-3 levels could be a useful tool to improve outcomes for patients with pulmonary fibrosis and other chronic lung diseases.
“We found that higher levels of omega-3 fatty acids in the blood, which reflects several weeks of dietary intake, were linked to better lung function and longer survival,” said researcher John Kim, MD, a pulmonary and critical care expert at UVA Health and the University of Virginia School of Medicine. “Our findings suggest omega-3 fatty acids might be a targetable risk factor in pulmonary fibrosis.”
Omega-3 and Pulmonary Fibrosis
Omega-3 fatty acids have already been linked to a host of health benefits. Studies have suggested, for example, that they may lower the risk of heart disease, stroke-causing blood clots, breast cancer and other cancers, Alzheimer’s disease and dementia.
Kim and his colleagues wanted to determine if omega-3s could play a protective role in interstitial lung disease, a group of chronic lung diseases that can lead to pulmonary fibrosis. A growing problem around the world, pulmonary fibrosis is an irreversible condition that leaves the lungs unable to exchange oxygen and carbon dioxide properly. This can cause patients to become short of breath, weak, unable to exercise and a host of other symptoms. Smoking is a major risk factor.

The researchers looked at anonymized data on patients with interstitial lung disease collected in the Pulmonary Fibrosis Foundation Registry, as well as information volunteered by patients at UVA Health and the University of Chicago.
In total, the scientists reviewed information on more than 300 people with interstitial lung disease. Most were men (pulmonary fibrosis is more common in men than women), and most suffered from “idiopathic” pulmonary fibrosis, one of the conditions that fall under the banner of interstitial lung disease.
The researchers found that higher levels of omega-3 fatty acids in the blood plasma were associated with better ability to exchange carbon dioxide and longer survival without the need for a lung transplant. This did not vary much regardless of smoking history or whether the patients had cardiovascular disease.
“Higher levels of omega-3 fatty acids were predictive of better clinical outcomes in pulmonary fibrosis,” Kim said. “These findings were consistent whether you had a history of cardiovascular disease, which suggests this may be specific to pulmonary fibrosis.”
The doctors say additional research is needed to understand just how omega-3s could be having this protective benefit. They are calling for clinical trials and more mechanistic studies to obtain additional insights and determine if omega-3 fatty acid drugs or dietary changes could improve patient outcomes.
“We need further research to determine if there are specific omega-3 fatty acids that may be beneficial and, if so, what are their underlying mechanisms,” Kim said. “Similar to other chronic diseases, we hope to determine whether nutrition related interventions can have a positive impact on pulmonary fibrosis.”

Throughout the day and night, cerebrospinal fluid (CSF) pulses through small fluid-filled channels surrounding blood vessels in the brain, called perivascular spaces, to flush out neuroinflammation and other neurological waste. A disruption to this vital process can lead to neurological dysfunction, cognitive decline, or developmental delays.
For the first time, researchers Dea Garic, PhD, and Mark Shen, PhD, both at the UNC School of Medicine’s Department of Psychiatry, discovered that infants with abnormally enlarged perivascular spaces have a 2.2 times greater chance of developing autism compared to infants with the same genetic risk. Their research also indicated that enlarged perivascular spaces in infancy are associated with sleep problems seven to 10 years after diagnosis.
“These results suggest that perivascular spaces could serve as an early marker for autism,” said Garic, assistant professor of psychiatry and a member of the Carolina Institute for Developmental Disabilities (CIDD).
The researchers studied infants at increased likelihood for developing autism, because they had an older sibling with autism. They followed these infants from 6-24 months of age, before the age of autism diagnosis. Their study, published in JAMA Network Open, found that thirty percent of infants who later developed autism had enlarged perivascular spaces by 12 months. By 24 months of age, nearly half of the infants diagnosed with autism had enlarged perivascular spaces.
The Importance of Cerebrospinal Fluid and Sleep
Starting ten years ago, there has been a resurgence of research on the important functions of CSF in regulating brain health and development. Shen’s lab was the first to report that excessive volume of CSF was evident at 6 months of age in infants who would later develop autism. The current study showed that excessive CSF volume at 6 months was linked to enlarged perivascular spaces at 24 months.
Every six hours, the brain expels a wave of CSF that flows through perivascular spaces to remove potentially harmful neuroinflammatory proteins, such as amyloid beta, from building up in the brain. The CSF cleansing process is especially efficient when we are asleep, as the majority of CSF circulation and clearance occurs during sleep.

Disrupted sleep, however, can reduce CSF clearance from perivascular spaces, leading to dilation or enlargement, but this has previously only been studied in animal studies or in human studies of adults. This is the first study of its kind in children.
Shen, senior author of the JAMA Network Open paper, and Garic hypothesized that CSF abnormalities in infancy would be related to later sleep problems, based on Shen’s earlier research. The current sleep analysis revealed children who had enlarged perivascular spaces at two years of age had higher rates of sleep disturbances at school age.
“Since autism is so highly linked with sleep problems, we were in this unique position to examine CSF dynamics and sleep,” said Garic, who is first author of the paper. “It was really striking to observe such a strong association separated by such a long period of time over childhood. But it really shows how perivascular spaces not only have an effect early in life, but they can have long term effects, too.”
New Clinical Relevance in Infancy
The research was done in conjunction with the Infant Brain Imaging Study (IBIS), a nationwide network of researchers investigating brain development, autism, and related developmental disabilities. The network consists of five universities, of which the University of North Carolina-Chapel Hill is the lead site.
For their study, Garic and Shen analyzed 870 MRIs from IBIS to measure excessive CSF volume and enlarged perivascular spaces. MRIs were obtained from babies during natural sleep at six, 12, and 24 months of age to observe changes over time.

The infant brain undergoes rapid development over this period. Previously, measurement of perivascular spaces was only thought to be clinically relevant for disorders of aging in older adults, such as in dementia. These findings suggest that younger populations may need to be considered and monitored for these types of brain abnormalities.
“Our findings were striking, given that neuroradiologists typically view enlarged perivascular spaces as a sign of neurodegeneration in adults, but this study reported it in toddlers,” said Garic. “This is an important aspect of brain development in the first years of life that should be monitored.”
Future Studies and Possibilities
Garic and Shen hypothesize that excess CSF volume is stagnant, or clogged, and not circulating through the brain as efficiently as it should. For their next research endeavor, the researchers are planning to once again use MRIs to measure CSF in a sleeping infant’s brain, but this time focusing on the physiology and speed of CSF flow throughout the brain.
The research team is also working with other collaborators to quantify the size of perivascular spaces and the severity of behavioral outcomes. The team also plans to extend their research to neurogenetic syndromes associated with autism, such as Fragile X syndrome and Down syndrome.
“Collectively our research has shown that CSF abnormalities in the first year of life could have downstream effects on a variety of outcomes, including later autism diagnosis, sleep problems, neuroinflammation, and possibly, other developmental disabilities,” said Shen.
This work was supported the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH), National Institute of Environmental Health Sciences (NIEHS), and the Simons Foundation.
Other researchers on this project include Joseph Piven, MD; Heather C. Hazlett, PhD; Martin Styner, PhD; Sun Hyung Kim, PhD; Joshua Rutsohn, PhD; and Leigh Anne Weisenfeld, MA; of the University of North Carolina — Chapel Hill; Robert C. McKinstry, MD, PhD; and Kelly N. Botteron, MD; of Washington University in St. Louis; Rebecca Slomowitz, MA; of the University of Denver; Jason Wolff, PhD; of the University of Minnesota; Leigh C. MacIntyre, BSc; of McGill University; Juhi Pandey, PhD; of University of Pennsylvania; and Tanya St. John, PhD; Annette M. Estes, PhD; Robert T. Schultz, PhD; and Stephen R. Dager, MD; of the University of Washington.

The NewsTens of thousands of women who are not pregnant are ordering abortion pills just in case they might need them someday, especially in states where access is threatened, according to a study published on Tuesday.After the Supreme Court overturned Roe v. Wade, more women began ordering abortion pills just in case they became pregnant, especially in states where abortion access was under threat.Evelyn Hockstein/ReutersWhy It MattersThe practice, known as advance provision, is relatively new and has increased significantly since the Supreme Court’s decision in 2022 to overturn the national right to abortion.In the study, published in the journal JAMA Internal Medicine, researchers evaluated data from Aid Access, a telehealth organization that has long provided abortion pills to women in the first 13 weeks of pregnancy and began offering the medication to women in the United States who weren’t pregnant in September 2021.Before May 2022, when a draft of the Supreme Court decision was leaked, Aid Access had received about 6,000 advance provision requests, averaging 25 per day. Since then, it has received over 42,000 requests, averaging 118 per day, said Dr. Abigail Aiken, an associate professor at the University of Texas at Austin and a co-author of the study.The biggest spikes in demand followed events that raised doubts about the future availability of abortion. Requests peaked in the weeks between the leak and the Supreme Court’s decision in June 2022, and in April 2023 after a flurry of court rulings in a lawsuit by abortion opponents seeking to curtail mifepristone, a key abortion pill, a case now before the Supreme Court.Rates of requests were highest in states where abortion bans were expected — even higher than in states that already had bans. Asked why they requested the pills, most women said to “ensure personal health and choice” and “prepare for possible abortion restrictions,” according to the study.“People were obviously paying attention and seeing the threat of abortion access either going away or being reduced where they were and thinking, ‘I need to get prepared for that,’” Dr. Aiken said.Behind the NumbersData from September 2021 through April 2023 showed 48,404 advance provision requests and 147,112 requests from women seeking to terminate existing pregnancies. (Women in both categories completed telehealth consultations and Aid Access evaluated their medical information before prescribing pills.)Advance provision requesters were more likely than those already pregnant to be 30 or older, white and childless, and to live in urban neighborhoods with lower poverty rates than the national average. That might be partly because Aid Access offers free or reduced-price services to pregnant patients who need financial assistance, while advance provision requesters were expected to pay the full $110 cost, Dr. Aiken said.And because few organizations offer advance provision, women from marginalized or lower-income communities might be less aware “that it’s even a thing you can do,” she said.Medication abortion typically involves two pills: mifepristone, which has a shelf life of three to five years, followed a day or two later by misoprostol, which has a shelf life of 18 to 24 months.Dr. Aiken said a subset of advance provision requesters — 937 women, two-thirds of them in states with abortion bans or restrictions — answered follow-up questions. Most still had the pills, but 58 had taken them and 55 had given them to someone else.About 60 percent took the pills before seven weeks of pregnancy, early in the recommended time frame. A vast majority reported having enough information, including about expected bleeding and cramping. All 58 said the pills worked. Five visited health care providers afterward, but none went to the hospital or had serious complications.Larger ImplicationsLegal scholars say advance provision may be legal in some states with abortion bans. “Many state abortion laws require a provider to know a person is pregnant,” three law professors — David S. Cohen, Greer Donley and Rachel Rebouché — wrote in an article to be published in the Stanford Law Review. However, they added, in some states, abortion providers might be legally vulnerable since they know that “the pills are prescribed to terminate a future pregnancy.”Abortion opponents object to advance provision and claim abortion medication is dangerous. Abortion rights supporters say prescribing it in case of future need, like antibiotics for traveler’s diarrhea, increases access and underscores that the pills are safe, as many studies show.