Publisher Health

Assessing how seriously injured a person is, involves weighing up lots of different parameters fast. If healthcare professionals could get support making fast-paced, life-critical decisions from an AI tool, more lives could be saved. This is shown by research from Chalmers University of Technology in Sweden, along with the University of Gothenburg and the University of Borås.
“If severely injured people are transported directly to a university hospital, the chances of survival increase, as there are resources to take care of all types of injuries. Therefore, we need to be able to better say who is severely injured, and who is not, so that everyone receives the right care and that resources are used in the best way,” says Anna Bakidou, doctoral student in the research group Care@Distance — Remote and Prehospital Digital Health at the Department of Electrical Engineering at Chalmers University of Technology.
In a recently published study, Anna Bakidou and her co-authors have developed five different mathematical models based on the data of adults who came into contact with ambulance care between 2013 and 2020. This data is from over 47,000 real events, retrieved from the Swedish Trauma Registry, which also showed where the people had been transported. By weighing up a number of complex variables, such as respiratory rate, injury type, blood pressure, age and gender, it turned out that all AI models could perform better than the clinical outcome — which were the transport decisions made by the ambulance staff at the time of the incident.
Many severely injured taken to regular hospitals
It turned out that 40 percent of the severely injured patients were not sent directly to a university hospital. At the same time, 45 percent of the non-severely injured were sent to university hospitals unnecessarily, as their injuries could have been taken care of in a regular hospital.
“Ambulance personnel are constantly faced with difficult and quick decisions. Our hope is that a more objective decision support system will be able to function as an ‘extra colleague’ that makes staff see more complex connections and think twice in cases where injuries can be difficult to perceive or assess,” says Anna Bakidou.
As an example, she mentions that younger people — who are often involved in traffic accidents — are frequently judged to be more severely injured than they are. On the other hand; older people, who are involved in events such as fall accidents, are often assessed as mildly injured — despite the fact that their condition can suddenly become life-threatening, due to consequences such as internal bleeding.

Several steps before the technology can be put into use
Although the mathematical models show that many human lives could potentially be saved, there is still a long way to go before ambulance staff can use the technology. A crucial step is to find methods to input all of the information quickly and easily into the AI tool, and for the service to be able to interact with the users in a good way.
“For example, can you talk to the tool to be able to have both hands free? How can existing routines and protocols be used to work together with the AI, and how can the advice to staff be updated when new data is added? We need to test and take these things into account when we proceed with more studies and prototype work,” says Anna Bakidou.
Before AI services could become part of everyday life for ambulance staff, large-scale clinical trials over time are also required.
“The regulations mean that it takes time and there is also a fear of AI. There can be serious consequences if things go wrong. Everything that is to be introduced into healthcare must be validated. At the same time, we know that some of the methods used today are not always the best. When it comes to ambulance care, there is not much research on AI, and we hope that our mathematical models will be able to contribute with support that is adapted to the work environment and that in the long run provides more equal care,” says co-author Stefan Candefjord, Associate Professor at the Department of Electrical Engineering at Chalmers.

How deeply someone can be hypnotized — known as hypnotizability — appears to be a stable trait that changes little throughout adulthood, much like personality and IQ. But now, for the first time, Stanford Medicine researchers have demonstrated a way to temporarily heighten hypnotizablity — potentially allowing more people to access the benefits of hypnosis-based therapy.
In the new study, to be published Jan. 4 in Nature Mental Health, the researchers found that less than two minutes of electrical stimulation targeting a precise area of the brain could boost participants’ hypnotizability for about one hour.
“We know hypnosis is an effective treatment for many different symptoms and disorders, in particular pain,” said Afik Faerman, PhD, a postdoctoral scholar in psychiatry and lead author of the study. “But we also know that not everyone benefits equally from hypnosis.”
Focused attention
Approximately two-thirds of adults are at least somewhat hypnotizable, and 15% are considered highly hypnotizable, meaning they score 9 or 10 on a standard 10-point measure of hypnotizability.
“Hypnosis is a state of highly focused attention, and higher hypnotizability improves the odds of your doing better with techniques using hypnosis,” said David Spiegel, MD, a professor of psychiatry and behavioral sciences and a senior author of the study.
Spiegel, the Jack, Lulu, and Sam Willson Professor in Medicine, has devoted decades to studying hypnotherapy and using it to help patients control pain, lower stress, stop smoking and more. Several years ago, Spiegel led a team that used brain imaging to uncover the neurobiological basis of the practice. They found that highly hypnotizable people had stronger functional connectivity between the left dorsolateral prefrontal cortex, which is involved in information processing and decision making; and the dorsal anterior cingulate cortex, involved in detecting stimuli.

“It made sense that people who naturally coordinate activity between these two regions would be able to concentrate more intently,” Spiegel said. “It’s because you’re coordinating what you are focusing on with the system that distracts you.”
Shifting a stable trait
With these insights, Spiegel teamed up with Nolan Williams, MD, associate professor of psychiatry and behavioral sciences, who has pioneered non-invasive neurostimulation techniques to treat conditions such as depression, obsessive-compulsive disorder and suicidal ideation.
The hope was that neurostimulation could alter even a stable trait like hypnotizability.
In the new study, the researchers recruited 80 participants with fibromyalgia, a chronic pain condition that can be treated with hypnotherapy. They excluded those who were already highly hypnotizable.
Half of the participants received transcranial magnetic stimulation, in which paddles applied to the scalp deliver electrical pulses to the brain. Specifically, they received two 46-second applications that delivered 800 pulses of electricity to a precise location in the left dorsolateral prefrontal cortex. The exact locations depended on the unique structure and activity of each person’s brain.

“A novel aspect of this trial is that we used the person’s own brain networks, based on brain imaging, to target the right spot,” said Williams, also a senior author of the study.
The other half of participants received a sham treatment with the same look and feel, but without electrical stimulation.
Hypnotizability was assessed by clinicians immediately before and after the treatments, with neither patients nor clinicians knowing who was in which group.
The researchers found that participants who received the neurostimulation showed a statistically significant increase in hypnotizability, scoring roughly one point higher. The sham group experienced no effect.
When the participants were assessed again one hour later, the effect had worn off and there was no longer a statistically significant difference between the two groups.
“We were pleasantly surprised that we were able to, with 92 seconds of stimulation, change a stable brain trait that people have been trying to change for 100 years,” Williams said. “We finally cracked the code on how to do it.”
The researchers plan to test whether different dosages of neurostimulation could enhance hypnotizability even more.
“It’s unusual to be able to change hypnotizability,” Spiegel said. A study of Stanford University students that began in the 1950s, for example, found that the trait remained relatively consistent when the students were tested 25 years later, as consistent as IQ over that time period. Recent research by Spiegel’s lab also suggests that hypnotizability may have a genetic basis.
Bigger implications
Clinically, a transient bump in hypnotizability may be enough to allow more people living with chronic pain to choose hypnosis as an alternative to long-term opioid use. Spiegel will follow up with the study participants to see how they fare in hypnotherapy.
The new results could have implications beyond hypnosis. Faerman noted that neurostimulation may be able to temporarily shift other stable traits or enhance people’s response to other forms of psychotherapy.
“As a clinical psychologist, my personal vision is that, in the future, patients come in, they go into a quick, non-invasive brain stimulation session, then they go in to see their psychologist,” he said. “Their benefit from treatment could be much higher.”
The study was supported by funding from the National Institute of Health (grant R33AT009305-03).

Overwhelming fear, sweaty palms, shortness of breath, rapid heart rate — these are the symptoms of a panic attack, which people with panic disorder have frequently and unexpectedly. Creating a map of the regions, neurons, and connections in the brain that mediate these panic attacks can provide guidance for developing more effective panic disorder therapeutics.
Now, Salk researchers have begun to construct that map by discovering a brain circuit that mediates panic disorder. This circuit consists of specialized neurons that send and receive a neuropeptide — a small protein that sends messages throughout the brain — called PACAP. What’s more, they determined that PACAP and the neurons that produce its receptor are possible druggable targets for new panic disorder treatments.
The findings were published in Nature Neuroscience on January 4, 2024.
“We’ve been exploring different areas of the brain to understand where panic attacks start,” says senior author Sung Han, associate professor at Salk. “Previously, we thought the amygdala, known as the brain’s fear center, was mainly responsible — but even people who have damage to their amygdala can still experience panic attacks, so we knew we needed to look elsewhere. Now, we’ve found a specific brain circuit outside of the amygdala that is linked to panic attacks and could inspire new panic disorder treatments that differ from current available panic disorder medications that typically target the brain’s serotonin system.”
To begin sketching out a panic disorder brain map, the researchers looked at a part of the brain called the lateral parabrachial nucleus (PBL) in the pons (part of the brain stem), which is known as the brain’s alarm center. Interestingly, this small brainstem area also controls breathing, heart rate, and body temperature.
It became evident that the PBL was likely implicated in generating panic and bringing about emotional and physical changes. Furthermore, they found that this brain area produces a neuropeptide, PACAP (pituitary adenylate cyclase-activating polypeptide), known as the master regulator of stress responses. But the link between these elements was still unclear, so the team turned to a mouse model of panic attacks to confirm and expand their proposed map.
“Emotional and stress-related behaviors have been associated with PACAP-expressing neurons in the past,” says co-first author Sukjae Kang, senior research associate in Han’s lab. “By mimicking panic attacks in the mice, we were able to watch those neurons’ activity and discover a unique connection between the PACAP brain circuit and panic disorder.”
They found that during a panic attack, PACAP-expressing neurons became activated. Once activated, they release PACAP neuropeptide messenger to another part of the brain called the dorsal raphe, where neurons expressing PACAP receptors reside. The released PACAP messengers activate those receptor neurons, thereby producing panic-associated behavioral and physical symptoms in the mice.

This connection between panic disorder and the PACAP brain circuit was an important step forward for mapping panic disorder in the brain, Han says. The team also found that by inhibiting PACAP signaling, they could disrupt the flow of PACAP neuropeptides and reduce panic symptoms — a promising finding for the future development of panic disorder-specific therapeutics.
According to Han, despite panic disorder’s categorization as an anxiety disorder, there are many ways that anxiety and panic are different — like how panic induces many physical symptoms, like shortness of breath, pounding heartrate, sweating, and nausea, but anxiety does not induce those symptoms. Or how panic attacks are uncontrollable and often spontaneous, while other anxiety disorders, like post-traumatic stress disorder (PTSD), are more memory-based and have predictable triggers. These differences, says Han, are why it is critical to construct this panic disorder brain map, so that researchers can create therapeutics specially tailored to panic disorder.
“We found that the activity of PACAP-producing neurons in the brain’s parabrachial nucleus is inhibited during anxiety conditions and traumatic memory events — the mouse’s amygdala actually directly inhibits those neurons,” says Han, who is also the Pioneer Fund Developmental Chair at Salk. “Because anxiety seems to be operating conversely to the panic brain circuit, it would be interesting to look at the interaction between anxiety and panic, since we need to explain now how people with anxiety disorder have a higher tendency to experience panic attack.”
The team is excited to explore PACAP-expressing neurons and PACAP neuropeptides as novel druggable targets for panic disorder. Additionally, they are hoping to further build out their map of panic disorder in the brain to see where the PACAP receptor-producing neurons in the dorsal raphe send their signals, and how other anxiety-related brain areas interact with the PACAP panic system.
Other authors include Jong-Hyun Kim (co-first author), Dong-Il Kim, and Benjamin Roberts of Salk.
The work was supported by the National Institutes of Mental Health (BRAINS grant 1R01MH116203) and the Simons Foundation (Bridge to Independence award SFARI #388708).

Autophagy, which declines with age, may hold more mysteries than researchers previously suspected. In the January 4th issue of Nature Aging, it was noted that scientists from the Buck Institute, Sanford Burnham Prebys and Rutgers University have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins — and ultimately affect aging.
“While this is very basic research, this work is a reminder that it is critical for us to understand whether we have the whole story about the different genes that have been related to aging or age-related diseases,” said Professor Malene Hansen, Ph.D., Buck’s chief scientific officer, who is also the study’s co-senior author. “If the mechanism we found is conserved in other organisms, we speculate that it may play a broader role in aging than has been previously appreciated and may provide a method to improve life span.”
These new observations provide another perspective to what was traditionally thought to be occurring during autophagy.
Autophagy is a cellular “housekeeping” process that promotes health by recycling or disposing of damaged DNA and RNA and other cellular components in a multi-step degradative process. It has been shown to be a key player in preventing aging and diseases of aging, including cancer, cardiovascular disease, diabetes and neurodegeneration. Notably, research has shown that autophagy genes are responsible for prolonged life span in a variety of long-lived organisms.
The classical explanation of how autophagy works is that the cellular “garbage” to be dealt with is sequestered in a membrane-surrounded vesicle, and ultimately delivered to lysosomes for degradation. However, Hansen, who has studied the role of autophagy in aging for most of her career, was intrigued by an accumulation of evidence that indicated that this was not the only process in which autophagy genes can function.
“There had been this growing notion over the last few years that genes in the early steps of autophagy were ‘moonlighting’ in processes outside of this classical lysosomal degradation,” she said. Additionally, while it is known that multiple autophagy genes are required for the increased life span, the tissue-specific roles of specific autophagy genes are not well defined.
To comprehensively investigate the role that autophagy genes play in neurons — a key cell type for neurodegenerative diseases — the team analyzed Caenorhabditis elegans, a tiny worm that is frequently used to model the genetics of aging and which has a very well-studied nervous system. The researchers specifically inhibited autophagy genes functioning at each step of the process in the neurons of the animals, and found that neuronal inhibition of early-acting, but not late-acting, autophagy genes, extended life span. These initial observations were made in Dr. Hansen’s lab at Sanford Burnham Prebys in La Jolla, California, before she moved to the Buck Institute in 2021.

An unexpected aspect was that this life span extension was accompanied by a reduction in aggregated protein in the neurons (an increase is associated with Huntington’s disease, for example), and an increase in the formation of so-called exophers. These giant vesicles extruded from neurons were identified in 2017 by Dr. Monica Driscoll, a collaborator and professor at Rutgers University.
“Exophers are thought to be essentially another cellular garbage disposal method, a mega-bag of trash,” said Dr. Caroline Kumsta, co-senior author and assistant professor at SBP. “When there is either too much trash accumulating in neurons, or when the normal ‘in-house’ garbage disposal system is broken, the cellular waste is then being thrown out in these exophers.”
Interestingly, worms that formed exophers had reduced protein aggregation and lived significantly longer. This finding suggests a link between this process of this massive disposal event to overall health, said Kumsta. The team found that this process was dependent on a protein called ATG-16.2.
The study identified several new functions for the autophagy protein ATG-16.2, including in exopher formation and life span determination, which led the team to speculate that this protein plays a nontraditional and unexpected role in the aging process. If this same mechanism is operating in other organisms, it may provide a method of manipulating autophagy genes to improve neuronal health and increase life span.
“But first we have to learn more — especially how ATG-16.2 is regulated and whether it is relevant in a broader sense, in other tissues and other species,” Hansen said. The Hansen and Kumsta teams are planning on following up with a number of longevity models, including nematodes, mammalian cell cultures, human blood and mice.
“Learning if there are multiple functions around autophagy genes like ATG-16.2 is going to be super important in developing potential therapies,” Kumsta said. “It is currently very basic biology, but that is where we are in terms of knowing what those genes do.”
The traditional explanation that aging and autophagy are linked because of lysosomal degradation may need to expand to include additional pathways, which would have to be targeted differently to address the diseases and the problems that are associated with that. “It will be important to know either way,” Hansen said. “The implications of such additional functions may hold a potential paradigm shift.”

The gut microbiome is so useful to human digestion and health that it is often called an extra digestive organ. This vast collection of bacteria and other microorganisms in the intestine helps us break down foods and produce nutrients or other metabolites that impact human health in a myriad of ways. New research from the University of Chicago shows that some groups of these microbial helpers are amazingly resourceful too, with a large repertoire of genes that help them generate energy for themselves and potentially influence human health as well.
The paper, published January 4, 2024, in Nature Microbiology, identified 22 metabolites that three distantly related families of gut bacteria use as alternatives to oxygen for respiration in the anaerobic environment of the gut. These bacteria also have up to hundreds of copies of genes for producing the enzymes that process these alternate metabolites — many more than have been measured in bacteria that live outside the gut. These results suggest that anaerobic gut bacteria may have the ability to produce energy from hundreds of other compounds as well.
“These are examples of some of the peculiar metabolisms that act on all these different metabolites produced by the gut microbiome,” said Sam Light, PhD, Neubauer Family Assistant Professor of Microbiology at UChicago and senior author of the study. “This is interesting because one of the main ways the microbiome impacts our health is by making or modifying these small molecules that can then enter our bloodstream and act like drugs.”
At the organism level, we typically think of respiration as the process of breathing in oxygen. At the cellular level, respiration describes an energy-generating biochemical process. Most cells use oxygen for respiration, but in anaerobic environments like the inside of the intestine, cells have evolved to use other molecules.
Cells possess two main types of metabolism to produce energy: fermentation and respiration. In fermentation, the cell breaks down molecules to generate energy directly. Respiration involves two molecules: an electron donor and an electron acceptor. A classic example of this process uses glucose as a donor and oxygen as the acceptor. The cells break down the glucose by shuttling extracted electrons through a series of steps before their final transfer to an oxygen molecule. This prompts the cell to generate ATP, or adenosine triphosphate: the basic source of energy for use and storage at the cellular level.
Most of the microbes living in the gut use fermentation, but there are also several known types of bacteria with respiratory metabolisms, including those that use carbon dioxide and sulfate electron acceptors. For the new study, Light and his colleagues analyzed a database of more than 1,500 genomes from a database of human gut bacteria. They saw a surprising distribution of genes that produce reductases, which are enzymes that use different respiratory electron acceptors. While most of the genomes encode just a few reductases, a small subset encodes more than 30 different ones. These bacteria weren’t closely related; they came from three distinct and distantly related families (Burkholderiaceae, Eggerthellaceae, and Erysipelotrichaceae) separated by hundreds of millions of years of evolutionary history.
These bacteria appear to be more resourceful than bacteria with respiratory metabolisms that live outside of a host organism, which mostly use inorganic compounds. The respiratory gut bacteria Light and team identified specialize in various organic metabolites, which makes sense given the constant food supply.

“There is so much organic matter in the gut that comes from the food we eat. It’s chemically complex, and you need more enzymes to accommodate it in that environment,” Light said. “We think this variety of genes enables gut bacteria to use a lot of different things that come their way.”
Some of the metabolites they use also have interesting implications for human health in the gut. People with type 2 diabetes, for example, have higher levels of an amino acid byproduct called imidazole propionate in their blood. Another metabolite, resveratrol, impacts several metabolic and immune system processes, and itaconate is produced by macrophages in response to infections.
Light hopes that more research like this will help us understand the function of different microbes in the gut, which can in turn be leveraged to improve health.
“I’m hoping our understanding of these different metabolisms and how they work will enable us to come up with strategies to intervene — either through the diet or pharmacologically — to modulate the flow of metabolites through these various pathways,” he said. “So, in whatever context, like type 2 diabetes or following an infection, we could control which metabolites are being produced to have a therapeutic benefit.”

Meet MYC, the shapeless protein responsible for making the majority of human cancer cases worse. UC Riverside researchers have found a way to rein it in, offering hope for a new era of treatments.
In healthy cells, MYC helps guide the process of transcription, in which genetic information is converted from DNA into RNA and, eventually, into proteins. “Normally, MYC’s activity is strictly controlled. In cancer cells, it becomes hyper active, and is not regulated properly,” said UCR associate professor of chemistry Min Xue.
“MYC is less like food for cancer cells and more like a steroid that promotes cancer’s rapid growth,” Xue said. “That is why MYC is a culprit in 75% of all human cancer cases.”
At the outset of this project the UCR research team believed that if they could dampen MYC’s hyperactivity, they could open a window in which the cancer could be controlled.
However, finding a way to control MYC was challenging because unlike most other proteins, MYC has no structure. “It’s basically a glob of randomness,” Xue said. “Conventional drug discovery pipelines rely on well-defined structures, and this does not exist for MYC.”
A new paper in the Journal of the American Chemical Society, on which Xue is the senior author, describes a peptide compound that binds to MYC and suppresses its activity.
In 2018, the researchers noticed that changing the rigidity and shape of a peptide improves its ability to interact with structureless protein targets such as MYC.

“Peptides can assume a variety of forms, shapes, and positions,” Xue said. “Once you bend and connect them to form rings, they cannot adopt other possible forms, so they then have a low level of randomness. This helps with the binding.”
In the paper, the team describes a new peptide that binds directly to MYC with what is called sub-micro-molar affinity, which is getting closer to the strength of an antibody. In other words, it is a very strong and specific interaction.
“We improved the binding performance of this peptide over previous versions by two orders of magnitude,” Xue said. “This makes it closer to our drug development goals.”
Currently, the researchers are using lipid nanoparticles to deliver the peptide into cells. These are small spheres made of fatty molecules, and they are not ideal for use as a drug. Going forward, the researchers are developing chemistry that improves the lead peptide’s ability to get inside cells.
Once the peptide is in the cell, it will bind to MYC, changing MYC’s physical properties and preventing it from performing transcription activities.
This work is possible in part with funding from the U.S. Department of Defense and congressionally directed medical research and from the National Institutes of Health.
Xue’s laboratory at UC Riverside develops molecular tools to better understand biology and uses that knowledge to perform drug discovery. He has long been interested in the chemistry of chaotic processes, which attracted him to the challenge of taming MYC.
“MYC represents chaos, basically, because it lacks structure. That, and its direct impact on so many types of cancer make it one of the holy grails of cancer drug development,” Xue said. “We are very excited that it is now within our grasp.”

With the simplicity of a blood test, it will be possible in the future to screen pregnant women for serious genetic diseases in their unborn children.
A research team from Odense University Hospital and the University of Southern Denmark has developed an innovative screening test. With a blood sample from the expectant mother, they can scrutinize all the genes in the fetus.
In the recently published results of the research project in the New England Journal of Medicine, the researchers analyzed blood samples from 36 pregnant women. The findings indicate that the new test, named desNIPT, has demonstrated effectiveness in identifying alterations in fetal genes — a leading factor in severe congenital diseases.
“With our novel approach, we can now screen for the majority of known serious genetic syndromes using a simple blood test from the pregnant woman. Typically, this would otherwise require resorting to chorionic villus sampling or amniocentesis,” states Ieva Miceikaité from the Department of Clinical Research, University of Southern Denmark.
“This implies that we now possess enhanced opportunities to pinpoint the genetic cause of developmental issues in the fetus,” she adds.
First-generation NIPT test
desNIPT represents an evolution of first-generation NIPT (Non-Invasive Prenatal Test) method, enhancing it with significant improvements. NIPT involves conducting the test without requiring chorionic villus sampling or amniocentesis, and it is administered prior to childbirth.

In this approach, the fetal DNA found in the bloodstream of the pregnant woman is scrutinized, fundamentally transforming the capacity to screen for diseases in unborn children in recent years.
DNA is released into the mother’s bloodstream through the placenta. Thanks to the remarkable sensitivity of the desNIPT test, researchers can now identify genetic abnormalities in the fetus even when the quantity of fetal DNA in the mother’s blood is minimal.
Genetic disorders in fetuses can be identified through analysis of the mother’s blood
At present, the first-generation Non-Invasive Prenatal Test (NIPT) is employed to screen the fetus for prevalent chromosomal disorders, predominantly focusing on conditions such as Down syndrome and a few others resulting from notable chromosomal alterations.
“Nevertheless, numerous congenital diseases arise from more subtle modifications in fetal DNA. To identify these, it is essential to examine all genes within the fetal genome,” explains Ieva Miceikaité.
This screening, referred to as exome sequencing, is presently limited to pregnancies where indications of abnormalities are noted during ultrasound scans. This restriction stems from the fact that the analysis currently necessitates either chorionic villus sampling or amniocentesis, both procedures associated with discomfort and a slight risk of miscarriage. As a result, numerous severe genetic syndromes frequently go undetected until after birth.

Our objective was to enhance non-invasive screening options for pregnant women. The new desNIPT test integrates the benefits of NIPT and exome sequencing, delivering comprehensive insights through a more straightforward test,” elucidates Ieva Miceikaité.
Achieving identical results with the more straightforward test.
Alongside her fellow researchers, Ieva Miceikaité monitored 36 pregnant women, analyzing blood samples taken during the 1st or 2nd trimester. In each pregnancy, ultrasound scans had revealed signs indicative of a potential serious genetic disease in the fetus.
Out of the 36 pregnancies, newly arising disease-causing alterations in the unborn child were identified in a total of 11 cases. Subsequently, the results from the desNIPT analysis were compared with those from conventional exome sequencing conducted through chorionic villus sampling or amniocentesis.
“The novel approach to screening pregnant women has been remarkably successful,” states Ieva Miceikaité, further noting:
“When applying the new analytical method, we successfully identified all gene variants responsible for diseases that were previously detected through invasive fetal examinations. In this regard, it has demonstrated comparable effectiveness to these invasive procedures.”
Promising future for prenatal screening
“The test opens the possibility of screening for many more genetic diseases in the future, including those that cannot be revealed by ultrasound scans,” explains Martin Larsen, leader of the project and associate professor at the Department of Clinical Research, University of Southern Denmark.
He envisions significant potential in deploying the test as a screening tool in conjunction with ultrasound examinations — the prevailing standard for all pregnant women — to guarantee a more thorough screening of expectant mothers before childbirth.
One notable challenge with numerous screening tests is their inconsistent precision, frequently resulting in unwarranted follow-up diagnostic examinations.
“We are highly optimistic as the study indicates that the desNIPT test is remarkably accurate. In the examined pregnant women, we did not observe any false-positive results,” states Martin Larsen.
Since this is a “proof-of-concept” study, the test needs validation in a larger study before it can be made available to pregnant women.
“At the outset, our aim was to establish the feasibility of sequencing the fetus’s genes through a blood sample from the pregnant woman. Presently, our focus is on validating the test through a larger study, as well as refining and scaling the methodology,” states Martin Larsen.

Tetraneutron is an elusive atomic nucleus consisting of four neutrons, whose existence has been highly debated by scientists. This stems primarily from our lack of knowledge about systems consisting of only neutrons, since most atomic nuclei are usually made of a combination of protons and neutrons. Scientists believe that the experimental observation of a tetraneutron could be the key to exploring new properties of atomic nuclei and answering the age-old question: Can a charge-neutral multineutron system ever exist?
Two recent experimental studies reported the presence of tetraneutrons in bound state and resonant state (a state that decays with time but lives long enough to be detected experimentally). However, theoretical studies indicate that tetraneutrons will not exist in a bound state if the interactions between neutrons are governed by our common understanding of two or three-body nuclear forces.
Intrigued, a team of researchers led by Associate Professor Hiroyuki Fujioka from Tokyo Institute of Technology set out to investigate the feasibility of bound tetraneutron emission. In their recent study published in Physical Review C, the team explored the possible emission rate of particle-stable tetraneutron via thermal neutron-induced fission of 235U (Uranium-235) in a nuclear reactor. “We are aware from previous literature that the dominant thermal fission process for 235U is binary fission, which leads to the emission of two heavy nuclear fragments together with 2.4 neutrons, on average. But there is a 0.2% probability of ternary fission, in which light nuclear fragments are emitted. We, therefore, chose this route for our experiment under the assumption that the hypothetically bound tetraneutron could be a ternary particle in uranium fission,” explains Dr. Fujioka.
The team adopted the well-known instrumental neutron activation analysis method, where a trace element in a chosen sample is irradiated and activated by the capture of thermal neutrons. For this study, 88SrCO3 was chosen as the target sample and was irradiated for two hours at a thermal power of 5 MW in a nuclear research reactor. The team also performed γ-ray spectroscopy for the irradiated sample to detect signals corresponding to a possible tetraneutron emission.
The 88Sr nuclei were expected to convert into 91Sr with a Q value (change in mass between the initial and final states of a reaction expressed in terms of energy units) of 20 MeV minus the binding energy of the tetraneutron. Since 91Sr is unstable, its radioactive decay followed by the release of γ-rays would indicate the emission of particle-stable tetraneutrons.
The γ-ray spectroscopy results for the irradiated 88Sr sample, however, did not show any photopeak corresponding to the formation of 91Sr. Based on this, the team estimated that if particle-stable tetraneutrons exist, their emission rate might be lower than 8 × 10−7 per fission at the 95% confidence level. They also suggested that improving the purity of samples and increasing the sensitivity of experimentation could help with the detection of subtle signals arising from tetraneutrons.
Dr. Fujioka says, “Our study showed that the instrumental neutron activation method in radiochemistry can be applied to address the open question in nuclear physics. We will improve the sensitivity further to seek for the elusive, charge-neutral system.”
While the team was not able to detect bound tetraneutrons, their work has laid a solid framework for future studies on the elusive tetraneutrons and other such systems.

When experiencing new things, the structure and function of our neurons and their connections are rapidly being remodeled. This process, known as synaptic plasticity, is critical for us to learn and adapt. However, these changes require a lot of energy.
Fortunately, our neurons are well-adapted to support these changes. Biological batteries known as mitochondria are strategically stabilized near sites of synaptic remodeling to ensure a local and efficient energy supply. However, how mitochondria are anchored near synapses was not known.
A team of scientists at Max Planck Florida Institute for Neuroscience has now identified a molecular anchor called VAP (vesicle-associated membrane protein-associated protein) that stabilizes mitochondria near synapses to support these remodeling projects. The identification of VAP as a molecular anchor has particular significance because a mutation in VAP leads to ALS (amyotrophic lateral sclerosis), a progressive motor neuron degeneration disease. This discovery, published in Nature Communications, not only sheds light on how memories are powered but opens up new research directions into ALS pathology.
Lead scientist of the work and Max Planck Florida Institute Research Group Leader, Dr. Vidhya Rangaraju, describes the implications, “While we started this study to understand fundamental properties of how memories are powered, our findings open important new directions for our research. We will investigate the cellular mechanisms of the cognitive symptoms that often occur with motor symptoms in ALS but have been severely understudied. We believe the tools and approaches that we have established will begin to shine light into this area.”
Stable mitochondria support the plasticity of synapses in dendrites
Neurons have an extensive, complex morphology and are constantly being remodeled. In order to energetically support these changes, mitochondria are anchored locally near synapses. This local stabilization allows the energy produced by the mitochondria to efficiently power local structural and functional changes in synapses during memory formation.
“This stability, however, is a unique feature of neuronal dendrites,” explains Ojasee Bapat, the study’s first author. “In neuronal axons, where mitochondria have been primarily studied, they are very mobile. We were interested in understanding how mitochondria are stabilized in dendrites and what this means for plasticity.”
The search for a molecular anchor

To address this knowledge gap, the team took an unbiased approach to identify proteins that might serve as an anchor to stabilize dendritic mitochondria. The team used a chemogenetic tool that chemically marked all proteins present near the outer shell of the mitochondria. They then took advantage of advanced proteomics to determine the identity of the marked proteins. This screen identified over 100 proteins that might be responsible for anchoring the mitochondria.
To narrow their search, they selected proteins for their ability to interact with the actin cytoskeleton. The actin cytoskeleton is a network of protein filaments localized near synapses in dendrites that help to define and remodel synaptic structure. Previous work of Dr. Rangaraju and others has shown that mitochondrial stability in dendrites depends on actin. Only a handful of the initially identified candidate proteins could bind to actin.
To determine if these proteins were essential to mitochondrial stabilization, the authors genetically removed them one by one from neurons and looked at the stability of mitochondria in dendrites. What they found was striking.
ALS-linked protein VAP stabilizes mitochondria to support plasticity
The team discovered that when they removed one particular protein, named VAP, the interaction of mitochondria with actin was reduced. Additionally, dendritic mitochondria were shorter and destabilized. Without VAP to anchor the mitochondria by tethering it to the actin cytoskeleton, the mitochondria drifted away from synapses over time.
Finally, the researchers investigated if mitochondrial instability caused by removing VAP affected synaptic plasticity, the structural and functional remodeling of synapses during memory formation. To test this question, the team induced remodeling in a cluster of synapses and compared the structural changes to neurons that lacked VAP. In neurons in which VAP was removed, the remodeling was dramatically impaired. Induced changes in the structure of synapses could not be maintained in the absence of VAP.

A link to ALS leads to new research directions
The discovery that VAP serves as a mitochondrial anchor and supports memory formation holds particular significance. A single mutation in VAP causes a familial form of ALS, a fatal progressive motor neuron degeneration disease. Although VAP is associated with this specific and rare familial cause of the disease, the discovery suggests that mitochondrial stability and energetic support of plasticity are key cellular pathways that might contribute to disease pathology.
“The fact that our unbiased screen for mitochondrial tethering to the cytoskeleton identified a protein linked to neurodegenerative disease suggests that mitochondrial stabilization is a critical element in neuronal function and health,” described Dr. Rangaraju. “We are motivated to expand our research focus to understand what happens in the brain when mitochondrial energy availability is disrupted. We think this focus has the potential to find common mechanisms of neurodegeneration in ALS as well as other neurological disorders.”

At EPFL’s School of Engineering, Professor Li Tang’s Laboratory of Biomaterials for Immunoengineering has made significant strides in cancer treatment research. In laboratory settings, this innovative CAR-T therapy has consistently eradicated cancerous tumors in mouse models. Separately, in on-going clinical trials, eleven patients seemed to achieve complete remission using this treatment, marking a success rate of 100% to date. Notably, evidence from the lab study, published in Nature Biotechnology, suggests the therapy’s long-term effectiveness, and indicates that its fabrication may be both quicker and more cost-effective than current methods.
At its core, CAR-T therapy involves modifying T-cells to target and eliminate specific cancer cells. These modified T-cells are equipped with Chimeric Antigen Receptors (CARs) that allow them to recognize and latch onto cancer cells, marking a significant departure from traditional treatments. “We’ve added another layer to the CAR-T cell therapy by bioengineering a more robust, supercharged immune cell that is particularly efficient at targeting and destroying tumor cells,” says Tang. The start-up Leman Biotech, co-founded by Tang and paper co-author Yugang Guo, aims to commercialize the treatment. The company has already garnered significant financial backing in its initial fundraising rounds.
Professor Li Tang’s groundbreaking research adds another dimension to this innovative approach. Traditional CAR-T cells, while effective against liquid cancers, face challenges in solid tumors — the cells wear themselves out and ultimately failing to fully destroy the cancer. Professor Tang’s research introduces CAR-T cells that excrete the IL-10 molecule, which is then ingested by the modified T cells. In other words, the cell has been engineered to produce its own medicine to keep healthy in the tumor’s hostile environment.
Surprisingly, the IL-10 molecule was traditionally viewed as an immune suppressant. But instead of inhibiting the immune response, Tang and his team have leveraged its unique metabolic reinforcement capabilities. This innovative twist bolsters the metabolism of the CAR-T cells. These metabolically armored treatments work immediately on existing tumors and have been shown to prevent future tumors from coming back.
Even after the reintroduction of tumor cells into the mouse models, the cells failed to establish themselves or show any malignancy. This underscores the lasting efficacy of the treatment, where the immune response remains vigilant and effectively neutralizes any renewed cancer threats. “The results in my lab are extremely exciting. We are convinced that this technology has the potential to save lives — as it has done so far with the 12 patients involved in our trial,” says Tang.
While current CAR-T cell therapy has proven effective and several treatments options are currently available for leukemia and other liquid cancers, it remains extremely expensive: The cost of one treatment is upwards of $500k. In contrast, the costs of this future treatment could be significantly lowered due to the fact that only five percent of the traditional dose is necessary for full recovery. Much of the costs come from the fabrication of relatively large amounts of these modified T-cells in expensive laboratory environments. “A small amount of blood from a patient could provide already enough cells to prepare CAR-T cell therapy with our technology. The next day you can already inject them back to the patient. It will be substantially less expensive and much faster to produce, saving more lives in the end” concludes Tang. Tang’s team and Leman Biotech is currently working toward that goal.