Wednesday, December 06, 2023

AI model predicts breast cancer risk without racial bias

RADIOLOGICAL SOCIETY OF NORTH AMERICA

Abnormal Mammogram — IMAGE:
ABNORMAL MAMMOGRAM.
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CREDIT: RSNA

CHICAGO – A deep learning artificial intelligence (AI) model that was developed using only mammogram image biomarkers accurately predicted both ductal carcinoma in situ (DCIS) and invasive carcinoma, according to research being presented today at the annual meeting of the Radiological Society of North America (RSNA). Additionally, the model showed no bias across multiple races.

Traditional breast cancer risk assessment models use information obtained from patient questionnaires, such as medical and reproductive history, to calculate a patient’s future risk of developing breast cancer.

“In the domain of precision medicine, risk-based screening has been elusive because we have not been able to accurately evaluate a woman’s risk of developing breast cancer,” said study lead author Leslie R. Lamb, M.D., M.Sc., a breast radiologist at Massachusetts General Hospital (MGH) in Boston. “Even the best existing traditional risk models do not perform well on the individual level.”

Traditional risk models have also demonstrated poor performance across different patient races, most likely due to the data used to develop the model.

“Traditional models likely have racial biases due to the populations on which they were developed,” Dr. Lamb said. “Several of the commonly used models were developed on predominantly European Caucasian populations.”

According to the American Cancer Society, Black women demonstrate the lowest 5-year relative survival rate for breast cancer among all racial and ethnic groups. This translates to a persistent 6% to 8% disparity in 5-year survival rates between Black and white women across all breast cancer types.

To accurately determine breast cancer risk, foster early detection and improve patient survival rates, it is important that risk models are developed that are applicable across different populations.

A deep learning AI risk assessment model developed using mammographic images alone can outperform traditional risk assessment models in future breast cancer development while also mitigating the racial biases seen in traditional models.

In the first study of its kind, Dr. Lamb and colleagues sought to assess the performance of an image-based deep learning risk assessment model in predicting both future invasive breast cancer and DCIS across multiple races.

The model’s performance was assessed by comparing areas under the receiver operating characteristic curve (AUC) with the DeLong test. The AUC score measures the predictive rate of the model on a scale of from 0 to 1. Multiple prior studies have estimated traditional risk model performance measured by AUC in the range of 0.59-0.62 for white women, with much lower performance in women of other races.

The multisite study included 129,340 routine bilateral screening mammograms performed in 71,479 women between 2009 to 2018 with five-year follow-up data. Patient demographics were obtained from electronic medical records, and instances of cancer were identified from the regional tumor registry.

The racial makeup of the study group included white (106,839 exams), Black (6,154 exams), Asian (6,435 exams), self-reported other races (6,257 exams) and unknown (3,655 exams). The mean age of the women was 59 years old.

The deep learning model consistently outperformed traditional risk models in predicting a woman’s risk of developing DCIS, which is early-stage breast cancer, and invasive breast cancer, which is cancer that has potential to spread.

“The model is able to translate the full diversity of subtle imaging biomarkers in the mammogram, beyond what the naked eye can see, that can predict a woman’s future risk of both DCIS and invasive breast cancer,” Dr. Lamb said. “The deep learning image-only risk model can provide increased access to more accurate, equitable and less costly risk assessment.”

The predictive rate of both DCIS and invasive cancer was 0.71 across all races. The AUC in predicting DCIS was 0.77 in non-white patients and 0.71 in white patients. The AUC in predicting invasive cancer was 0.72 in non-white patients and 0.71 in white patients.

“This is a particularly exciting domain for AI, as it demonstrates the opportunity to apply ‘AI for good’—to reduce well-known racial disparities in risk assessment,” said senior author Constance D. Lehman, M.D., Ph.D., a breast radiologist at MGH. “We are now poised to translate these findings into improved clinical care for our patients.”

Additional co-authors are Sarah F. Mercaldo, Ph.D., and Andrew R. Carney, M.S.

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Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23.

RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org)

Editor’s note: The data in these releases may differ from those in the published abstract and those actually presented at the meeting, as researchers continue to update their data right up until the meeting. To ensure you are using the most up-to-date information, please call the RSNA Newsroom at 1-312-791-6610.

For patient-friendly information on breast imaging, visit RadiologyInfo.org.

Regular screening mammograms significantly reduce breast cancer deaths

Reports and Proceedings

RADIOLOGICAL SOCIETY OF NORTH AMERICA

CHICAGO – Breast cancer mortality is significantly reduced when women regularly attend screening mammograms, according to research being presented today at the annual meeting of the Radiological Society of North America (RSNA).

Early detection of breast cancer, before symptoms are present, is key to survivability. According to the American Cancer Society, women between the ages of 45 and 54 should get mammograms every year. Women who are 55 years and older can switch to every other year or continue with annual mammograms. Skipping just one scheduled mammogram could result in a more advanced breast cancer diagnosis, significantly impacting a patient’s chance of survival.

“The purpose of mammography is to detect breast cancer during the few years it can be seen on a mammogram, but before symptoms are apparent,” said study author Robert A. Smith, Ph.D., senior vice president and director of the American Cancer Society Center for Cancer Screening in Atlanta, Georgia. “If a woman unknowingly has breast cancer and misses or postpones her mammogram during this time when she has no symptoms, but her breast cancer is growing and perhaps spreading, then the window for early detection will be lost.”

Even though regular mammograms are an important factor in early breast cancer detection, there are still many barriers that restrict women from receiving this preventative care, including access and work or family obligations.

“It is challenging to keep track of your schedule, and in the U.S., many women do not receive reminders. Further, for all of us, the obligations of work and family compete with our scheduled health care,” Dr. Smith said.

Dr. Smith and colleagues sought to identify the exact impact of missing even one mammogram.

The researchers obtained women’s screening history from oncology centers throughout Sweden for a period from 1992 to 2016. A total of 36,079 breast cancer patients were included in the study.

Using data from the Swedish Cause of Death Register, the researchers identified 4,564 breast cancer deaths among the patients included in the study.

The researchers then tracked all of the women’s participation in five or fewer most recent invitations for breast cancer screening prior to cancer diagnosis.

Women who attended all their invited screening mammograms had a survivability rate of over 80%. Women who didn’t participate in any screenings had a survival rate that ranged from 59.1% to 77.6%.

Women who attended all five screening mammograms saw a 72% reduction in the risk of dying from breast cancer compared to women who didn’t participate in any screening mammograms. Even after conservative adjustment for potential self-selection factors, there was a highly significant 66% reduction in the risk of breast cancer death.

“Women who attended all five previous mammography examinations prior to a diagnosis of breast cancer were nearly three times less likely to die from breast cancer compared with women who had not attended any examinations, and each additional examination attended among the five previous examinations conferred an additive protective effect against dying from breast cancer,” Dr. Smith said.

The researchers stressed that imaging facilities should prioritize getting patients in for screening at the earliest opportunity. This is especially important when women have to cancel their appointments. Facilities should reschedule these screening mammograms for the next earliest available appointment.

“These findings show that as much as possible, adherence to regular mammography screening is the very best insurance a woman has against being diagnosed with an advanced breast cancer that could be life-threatening,” Dr. Smith said.

Co-authors are Stephen W. Duffy, M.Sc., Amy Ming-Fang Yen, Ph.D., László Tabár, M.D., Abbie Ting-Yu, Ph.D., Sam Li-Sheng Chen, Ph.D., Chen-Yant Hsu, M.D., Peter B. Dean, M.D., and Tony Hsiu-His Chen, Ph.D.

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Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23.

For patient-friendly information on breast cancer screening with mammography, visit RadiologyInfo.org.

Artificial intelligence paves way for new medicines

Peer-Reviewed Publication

LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN

Researchers have developed an AI model that can predict where a drug molecule can be chemically altered.

A team of researchers from LMU, ETH Zurich, and Roche Pharma Research and Early Development (pRED) Basel has used artificial intelligence (AI) to develop an innovative method that predicts the optimal method for synthesizing drug molecules. “This method has the potential to significantly reduce the number of required lab experiments, thereby increasing both the efficiency and sustainability of chemical synthesis,” says David Nippa, lead author of the corresponding paper, which has been published in the journal Nature Chemistry. Nippa is a doctoral student in Dr. David Konrad’s research group at the Faculty of Chemistry and Pharmacy at LMU and at Roche.

Active pharmaceutical ingredients typically consist of a framework to which functional groups are attached. These groups enable a specific biological function. To achieve new or improved medical effects, functional groups are altered and added to new positions in the framework. However, this process is particularly challenging in chemistry, as the frameworks, which mainly consist of carbon and hydrogen atoms, are hardly reactive themselves. One method of activating the framework is the so-called borylation reaction. In this process, a chemical group containing the element boron is attached to a carbon atom of the framework. This boron group can then be replaced by a variety of medically effective groups. Although borylation has great potential, it is difficult to control in the lab.

Together with Kenneth Atz, a doctoral student at ETH Zurich, David Nippa developed an AI model that was trained on data from trustworthy scientific works and experiments from an automated lab at Roche. It can successfully predict the position of borylation for any molecule and provides the optimal conditions for the chemical transformation. “Interestingly, the predictions improved when the three-dimensional information of the starting materials were taken into account, not just their two-dimensional chemical formulas,” says Atz.

The method has already been successfully used to identify positions in existing active ingredients where additional active groups can be introduced. This helps researchers develop new and more effective variants of known drug active ingredients more quickly.

JOURNAL

Nature

DOI

10.1038/s41557-023-01360-5

ARTICLE TITLE

Enabling late-stage drug diversification by high-throughput experimentation with geometric deep learning

AI may aid in diagnosing adolescents with ADHD

Reports and Proceedings

RADIOLOGICAL SOCIETY OF NORTH AMERICA

Infographic - AI May Aid in Diagnosing Adolescents with ADHD — IMAGE:
USING ARTIFICIAL INTELLIGENCE (AI) TO ANALYZE SPECIALIZED BRAIN MRI SCANS OF ADOLESCENTS WITH AND WITHOUT ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD), RESEARCHERS FOUND SIGNIFICANT DIFFERENCES IN NINE BRAIN WHITE MATTER TRACTS IN INDIVIDUALS WITH ADHD.
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CREDIT: RSNA

CHICAGO – Using artificial intelligence (AI) to analyze specialized brain MRI scans of adolescents with and without attention-deficit/hyperactivity disorder (ADHD), researchers found significant differences in nine brain white matter tracts in individuals with ADHD. Results of the study will be presented today at the annual meeting of the Radiological Society of North America (RSNA).

ADHD is a common disorder often diagnosed in childhood and continuing into adulthood, according to the Centers for Disease Control and Prevention. In the U.S., an estimated 5.7 million children and adolescents between the ages of 6 and 17 have been diagnosed with ADHD.

“ADHD often manifests at an early age and can have a massive impact on someone’s quality of life and ability to function in society,” said study co-author Justin Huynh, M.S., a research specialist in the Department of Neuroradiology at the University of California, San Francisco, and medical student at the Carle Illinois College of Medicine at Urbana-Champaign. “It is also becoming increasingly prevalent in society among today’s youth, with the influx of smartphones and other distracting devices readily accessible.”

Children with ADHD may have trouble paying attention, controlling impulsive behaviors or regulating activity. Early diagnosis and intervention are key to managing the condition.

“ADHD is extremely difficult to diagnose and relies on subjective self-reported surveys,” Huynh said. “There is definitely an unmet need for more objective metrics for diagnosis. That’s the gap we are trying to fill.”

Huynh said this is the first study to apply deep learning, a type of AI, to identify markers of ADHD in the multi-institutional Adolescent Brain Cognitive Development (ABCD) Study, which includes brain imaging, clinical surveys and other data on over 11,000 adolescents from 21 research sites in the U.S. The brain imaging data included a specialized type of MRI called diffusion-weighted imaging (DWI).

“Prior research studies using AI to detect ADHD have not been successful due to a small sample size and the complexity of the disorder,” Huynh said.

The research team selected a group of 1,704 individuals from the ABCD dataset, including adolescents with and without ADHD. Using DWI scans, the researchers extracted fractional anisotropy (FA) measurements along 30 major white matter tracts in the brain. FA is a measure of how water molecules move along the fibers of white matter tracts.

The FA values from 1,371 individuals were used as input for training a deep-learning AI model, which was then tested on 333 patients, including 193 diagnosed with ADHD and 140 without. ADHD diagnoses were determined by the Brief Problem Monitor assessment, a rating tool used for monitoring a child’s functioning and their responses to interventions.

With the help of AI, the researchers discovered that in patients with ADHD, FA values were significantly elevated in nine white matter tracts.

“These differences in MRI signatures in individuals with ADHD have never been seen before at this level of detail,” Huynh said. “In general, the abnormalities seen in the nine white matter tracts coincide with the symptoms of ADHD.”

The researchers intend to continue obtaining data from the rest of the individuals in the ABCD dataset, comparing the performance of additional AI models.

“Many people feel that they have ADHD, but it is undiagnosed due to the subjective nature of the available diagnostic tests,” Huynh said. “This method provides a promising step towards finding imaging biomarkers that can be used to diagnose ADHD in a quantitative, objective diagnostic framework,” Huynh said.

Co-authors are Pierre F. Nedelec, M.S., M.T.M., Samuel Lashof-Regas, Michael Romano, M.D., Ph.D., Leo P. Sugrue, M.D., Ph.D., and Andreas M. Rauschecker, M.D., Ph.D.

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Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23.

For patient-friendly information on brain MRI, visit RadiologyInfo.org.

Plants recruit distinct chemical activities of coumarins under different soil pHs

Peer-Reviewed Publication

LEIBNIZ INSTITUTE OF PLANT GENETICS AND CROP PLANT RESEARCH

Iron uptake — IMAGE:
COUMARIN BIOSYNTHESIS IN ROOTS RESPONDS TO ENVIRONMENTAL PH CONDITIONS. UNDER SLIGHTLY ACIDIC CONDITIONS (LOW PH), PLANTS PRODUCE THE SUPERIOR FERRIC IRON (FE3+) REDUCTANT SIDERETIN, WHICH COMPLEMENTS FE3+ REDUCTION BY THE MEMBRANE-BOUND REDUCTASE FRO2. AT NEUTRAL TO ALKALINE CONDITIONS, FRAXETIN IS SYNTHESIZED TO MAINTAIN THE MOBILIZATION OF POORLY SOLUBLE IRON SOURCES FOR FURTHER REDUCTION BY FRO2.
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CREDIT: IPK LEIBNIZ INSTITUTE

Plants have two main uptake mechanisms to obtain iron (Fe) from the soils. The type of strategy employed depends on the botanical classification of the plant. In the so-called strategy-I mechanism, plants must first reduce the trivalent iron (Fe3+) into bivalent iron (Fe2+). Only then can Fe2+ be taken up by roots as a free ion. This strategy is used by non-Poaceae plants such as oilseed rape and the model plant Arabidopsis thaliana. Grasses, which belong to the Poaceae familiy, employ a so-called strategy II. These plants secrete chelating compounds, which can be reuptaken once chelated with Fe3+. Thus, no reduction step is required for Fe import into root cells.

"Interestingly, some Strategy-I plants also release metabolites into the soil through their roots when they suffer from Fe deficiency. Some of these are coumarins," explains IPK scientist Dr. Ricardo Giehl, co-head of the "Molecular Plant Nutrition" working group. However, the physiological role of these coumarins has not yet been sufficiently clarified.

In their work, the researchers were able to show that the main function of two coumarins released in response to Fe deficiency is largely dependent on the external pH. Under slightly acidic conditions, coumarins, especially sideretin, help to sustain Fe3+ reduction. Here, sideretin works together with the membrane-bound enzyme FERRIC REDUCTION OXIDASE 2 (FRO2) to efficiently Fe2+ uptake into the roots. If the medium is alkaline, the biosynthesis of coumarins is shifted from sideretin to fraxetin, a response that the research team found to depend on the transcription factor MYB72. At alkaline pH, sideretin loses both its ability to reduce and even to solubilize Fe3+ from precipitated sources, while fraxetin retains a high Fe3+ mobilization capacity under such pH conditions. Therefore, rather than reducing Fe3+ directly, the main function of fraxetin is to provide soluble Fe(III)-chelates for FRO2-mediated reduction.

"Our study shows that by adjusting coumarin biosynthesis, plants recruit specific functions depending on the prevailing pH of the soil," says Dr. Ricardo Giehl. If the conditions are slightly acidic, plants favor the synthesis of the superior Fe3+ reductant sideretin, while at high pH they direct synthesis towards fraxetin, which retains high Fe3+ mobilization capacity even under alkaline conditions.

With their work, the researchers provide valuable insights into environment-dependent fine regulation of metabolite biosynthesis and thus help to further understand how plants adapt to different pH conditions in the soil. The results open up new possibilities for the targeted improvement of plant productivity and plant health under variable soil conditions.

JOURNAL

The Plant Cell

DOI

10.1093/plcell/koad279

ARTICLE TITLE

Plants recruit distinct chemical activities of coumarins under different soil pHs

Football conference celebrates the women’s game

On Monday 11 December, Football - A Woman's Game will see researchers and practitioners from a range of disciplines share their experiences and knowledge

Meeting Announcement

STAFFORDSHIRE UNIVERSITY

An event showcasing the latest scientific research and best practices in women’s football takes place at Staffordshire University next month.

On Monday 11 December, Football - A Woman's Game will see researchers and practitioners from a range of disciplines share their experiences and knowledge.

Speakers will cover a wide variety of topics, including sport psychology in the Women’s Super League, menstrual cycle and performance, why we need women’s football boots, and stadium attendance in elite women’s football.

The conference has been organised by Dr Jacky Forsyth, Associate Professor of Exercise Physiology at Staffordshire University. She explained: “For continued success in women’s football, we need to both share our best practices, and apply cutting-edge, evidence-based, scientific information to maximise the performance potential of the footballer.

“This event is essential for anyone involved in women’s football, including coaches, physiotherapists, nutritionists, sports scientists, coach developers, technical directors, general managers, governing body personnel and club owners from grassroots to elite level, as well as the footballers themselves.”

The conference is supported and funded by Erasmus+ Sport, as part of the European Women in Sport (E-WinS) project which brings together nine universities and sports organisations to explore women’s and girls’ football across six countries.

As part of this, academics from Staffordshire University led a study involving more than 1,100 players, coaches and managers from grassroots to elite level clubs in Bulgaria, England, Finland, France, Poland and Spain. The research focussed on financial aspects, such as sponsorship, media coverage and visibility of women’s football, as well as performance aspects, which includes information on the menstrual cycle, hormonal contraception, pregnancy and childcare.

Based on the findings Dr Forsyth and colleagues have created educational tools and a database to share best practices and are supporting local clubs – including Stoke City FC Women, Port Vale FC Women and the University’s own women’s team – with their development

Dr Forsyth’s research focuses on the key influences which impact women in sport and exercise. She is co-founder of the Women in Sport and Exercise Academic Network (WiSEAN), co-author of the book, The Exercising Female: Science and its Application, and is co-editor of a new book, coming out in 2025, Women’s Football: From Science to High Performance.

Dr Forsyth added: “Currently, less than 1% of research spending on football is on women, despite the elite women’s game having grown in popularity in recent years. For this reason, it is important to continue high-level research on women’s football and events like this are an integral part of levelling the playing field.”

‘Football – A Woman’s Game’ takes place on Monday 11 Dec 2023, 9am to 5pm, at Staffordshire University’s Science Centre, Leek Road, Stoke-on-Trent, ST4 2DF – see the full agenda.

One in seven male gym goers consider impact on fertility

Three quarters would change workouts or supplement use if they knew it had long-term effect

Peer-Reviewed Publication

UNIVERSITY OF BIRMINGHAM

Young male gym users are largely unaware of the risks of their lifestyle on their fertility, a new study shows.

New results from a survey of 152 gym enthusiasts, published in Reproductive BioMedicine Online found that men were largely unaware of the risks to their fertility from aspects of gym lifestyle including protein supplements, which can contain high levels of estrogen, used by 79% of male respondents.

When questioned about their concern about fertility, more than half (52%) of male participants said that they had thought about their fertility before. However, only 14% of men who took part had considered how gym routines or supplement use might impact on fertility.

Further data shows that there was a significant difference in responses about whether the benefits of gym routines and supplements were more important to them than fertility, with 38% disagreeing and 28% agreeing. Female participants meanwhile were more aware of the impact of gym lifestyle on male fertility.

Dr Meurig Gallagher from the University of Birmingham and lead author of the study said:

“Being healthy and having a healthy lifestyle is a good thing. In the context of male fertility, the concern is over the increasing use of protein supplements. The main concern is the high levels of the female hormone estrogen that comes from both whey and soy protein supplements. Too much female hormone can cause problems with the amount and quality of sperm that a man can produce. Many protein supplements that can be bought have been found to be contaminated by anabolic steroids, which can cause reduced sperm count, shrunken testicles, and erectile dysfunction amongst other things.

“Infertility is a problem of increasing concern, affecting 1 in 6 people worldwide according to the World Health Organisation. Globally, there is limited understanding of the fact that men contribute to half of these cases of infertility.

“The major finding from this study is that there is a significant lack of awareness of male reproductive health in the young adult population we surveyed. While people were aware of the problems associated with anabolic steroid use, very few understood that gym protein supplementation can have negative effects.

Professor Jackson Kirkman-Brown from the University of Birmingham and author of the paper said:

“We found that men are genuinely curious about their fertility when prompted, but that they don’t think about it on their own – likely because societally people still think of fertility as a ‘female issue’ and (incorrectly) believe that men’s fertility doesn’t change throughout their lifetimes.”

“It’s important that people don’t see this as a reason not to be healthy or get exercise – but people should try and educate themselves about any form of supplementation they take, whether that is protein, vitamins or anything else. In general, most data would suggest it's better to eat unconcentrated natural food sources of protein, as these are also less likely to be contaminated at a high level with any environmental pollutants. For example, if you are eating a routine diet, roast chicken would be a good source of protein as opposed to a concentrated protein bar or shake.”

JOURNAL

Reproductive BioMedicine Online

DOI

10.1016/j.rbmo.2023.103623

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Gym lifestyle factors and male reproductive health: a study into young adult usage and perceptions

Female toxin-producing newts are surprisingly more poisonous than males

Female Taricha newts produce more tetrodotoxin than males, suggesting it could be a signal as well as a defense

Peer-Reviewed Publication

FRONTIERS

Tetrodotoxin, the neurotoxin that makes a blue-ringed octopus deadly, also protects Taricha newts — but we don’t understand how they produce it, or what purposes it serves for them. A first step to answering these questions is understanding whether different levels appear in males and females. In sexually reproducing animals, dimorphic traits such as color or canine tooth size can be key for survival and reproductive fitness. Investigating whether toxin production is a sexually dimorphic trait in newts gets us closer to understanding it.

“It had long been considered that newts’ toxin concentrations do not change in their lifetime and that males and females tend to have the same toxin concentrations. Now, we have shown that female newts actually contain more toxin than male newts,” said Dr Gary Bucciarelli of the University of California Davis, corresponding author of the article in Frontiers in Amphibian and Reptile Science. “We observed significantly greater and more drastically fluctuating toxin concentrations in females, which may have numerous causes, like mate selection.”

A toxic trait

The scientists already knew that Taricha newts were sexually dimorphic in other traits, like tail height, size, and mass. The tetrodotoxin seeps from the newts’ skin, so they took small samples from more than 850 newts across 38 different sites in California. They recorded sex, size, mass, and tail height for all newts, and whether female newts were pregnant. They also marked newts that had been captured and released so they would know which newts had previously been sampled.

They analyzed the skin to quantify the levels of toxin present and compared this between males and females. They also analyzed the relationship between the variables already known to be sexually dimorphic and toxin levels, and how toxin levels changed at sites where it was possible to sample more than once across the breeding season.

The female is deadlier than the male

They found that females carried more toxin than males. The differences in levels produced by females were not significant, compared to those between females and males. Males and females’ levels fluctuated at the same times and in the same direction, but the change in females’ levels of toxin was greater.

“For would-be predators, these higher concentrations pose a serious threat,” said Bucciarelli, confirming that this means female newts are more dangerous than males. “Taricha newts should not be handled unless by knowledgeable personnel, because they can contain up 54 milligrams of tetrodotoxin per individual. Doses up to 42 micrograms per kilo of bodyweight can lead to hospitalization or death.”

Tetrodotoxin also appeared to interact with other sexually dimorphic traits, suggesting that there may be a cost to high toxin levels: heavier newts produced higher levels of the toxin than lighter newts. The median concentration of toxin was always higher in females regardless of size or weight.

The females’ higher levels of toxin, and the similarity of levels between different females, indicates that the mechanisms of toxin production could be different between the sexes. It’s possible that resources needed to produce the toxin are invested differently by females, or females’ skin may be able to carry more toxin. Higher levels of toxin could protect females that are vulnerable while reproducing, or they may make it possible for females to transfer toxin-producing bacteria to eggs, potentially protecting their offspring.

Pick your poison

Although the toxin has previously only been thought of as a defense against snakes, the sex differences and fluctuating levels of toxin suggest it may have a more complex role. For example, the toxin may act as a cue that helps newts decide where they seek mates and which mates they choose.

“Taricha newts’ breeding patterns are highly dependent on precipitation patterns,” said Bucciarelli. “Given the drought conditions of California, we did not always have a balanced design when field sampling. However, we feel the pattern is still very strong.”

“Our next plan is to explore how drought and fire affect newts and their toxin concentrations and how each sex responds to these natural disasters.”

JOURNAL

Frontiers in Amphibian and Reptile Science

DOI

10.3389/famrs.2023.1279848

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

An amphibian toxin phenotype is sexually dimorphic and shows seasonal concordant change between sexes

ARTICLE PUBLICATION DATE

28-Nov-2023

COI STATEMENT

The authors GB, LK declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision

Yale study gives grandmother gecko a place of honor — and a new name

Peer-Reviewed Publication

YALE UNIVERSITY

New Haven, Conn. — Yale paleontologists have identified a new fossil lizard, found in the western United States, which they say was an ancestor of modern geckos. And they gave it a name that honors the lead researcher’s grandmother and great aunt.

The discovery of the new species, which they named Helioscopus dickersonae, suggests that gecko ancestors appeared in North America much earlier than previously known.

“This discovery emerged from a larger investigation of two fossil lizard skulls from Dinosaur National Monument in Utah,” said Dalton Meyer, a graduate student in Yale’s Department of Earth and Planetary Sciences and first author of a study in the journal Proceedings of the Royal Society B.

“These skulls had both been previously described as part of a European genus of skink ancestors, but we wanted to investigate that further with 3D data,” Meyer said.

Specifically, Meyer and his colleagues used computed tomography (CT) scans to develop 3D images of the skulls, which both dated back to the late Jurassic period, 163.5 to 145 million years ago. While one of the skulls was indeed an early skink, the researchers found, the other was not.

“It is one of the earliest known gecko relatives in the fossil record,” Meyer said. “This means that the gecko line made it to North America nearly 100 million years before the prior known earliest record.”

Scientifically, the discovery also offers vital information about specialized physical features of the gecko skull and how they developed. For example, unlike modern geckos, Helioscopus dickersonae was not primarily nocturnal. It had a prominent pineal foramen — a hole in the top of its head that many lizard species use to sense sunlight and judge the length of daylight hours.

Helioscopus dickersonae, Meyer said, was likely similar in appearance to banded geckos or leopard geckos, in that it didn’t have the adhesive toe pads that many modern geckos have. Based on more complete fossil skeletons from similar species found in Europe, he speculated that Helioscopus dickersonae may have been a skilled tree climber even without the toe pads.

Yet much remains unknown about how this early gecko fared in North America, other than the fact that it went extinct sometime within 90 million years of its arrival on the continent. Nothing like Helioscopus dickersonae appears in the fossil record in the Cretaceous period, which followed the Jurassic.

In naming the new species, Meyer chose “helioscopus,” which roughly translates into “sun watcher,” and “dickersonae,” which honors his grandmother, Helen Dickerson, his great aunt, Shirley Dickerson, and Mary Cynthia Dickerson (no relation), who was the first curator of herpetology at the American Museum of Natural History in New York City.

“Both my grandmother and great aunt were extremely important people in my life, and my great aunt passed away while I was in the early stages of working on this fossil,” Meyer said. “I was truly honored to have a chance to get to use their family name in this new species, in part as a memorial that will now persist long after I am gone.”

Co-authors of the study are Yale graduate students Chase Brownstein and Kelsey Jenkins. The study’s senior author is Jacques Gauthier, professor of Earth and planetary sciences in Yale’s Faculty of Arts and Sciences and curator-in-charge for reptiles at the Yale Peabody Museum.

JOURNAL

Proceedings of the Royal Society B Biological Sciences

Fralin Biomedical Research Institute at VTC scientist identifies a connection in the brain between stress and emotional eating

In a study published in Nature Communications, Assistant Professor Sora Shin describes the role of a molecule in the brain responsible for triggering overconsumption of comfort foods after a threatening event

Peer-Reviewed Publication

VIRGINIA TECH

Sora Shin, In-Jee You, Yeeun Bae — IMAGE:
(FROM LEFT) SORA SHIN, ASSISTANT PROFESSOR AT THE FRALIN BIOMEDICAL RESEARCH INSTITUTE AT VTC; HER FORMER RESEARCH ASSOCIATE IN-JEE YOU; AND GRADUATE STUDENT YEEUN BAE AUTHORED A PAPER PUBLISHED IN NATURE COMMUNICATIONS THAT IDENTIFIES A CONNECTION IN THE BRAIN BETWEEN THREATENING EVENTS AND THE STRONG DESIRE TO OVEREAT HIGH-FAT FOODS.
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CREDIT: PHOTO BY CLAYTON METZ FOR VIRGINIA TECH.

If you’ve had a near miss accident in your car or suffered the intimidation of a menacing person, you’ve probably felt it — a psychological reaction to a threat called a fight or flight response. Your heart rate climbs, anxiety washes over you, you might shake or sweat.

But hours after that stress passes, you may feel another response — a powerful desire for comfort food, that highly processed, high-fat stuff you know isn’t good for you. It can relieve stress and tension and provide a sense of control. Emotional eating following a stress-triggering interaction is familiar to many of us, and to scientists as well.

But how a threat signals your brain to want comfort food has been unknown.

Now, a Virginia Tech scientist has pinpointed a molecule found in a region of the brain called the hypothalamus that is connected to changes in the brain that lead to emotional overeating. Sora Shin, assistant professor at the Fralin Biomedical Research Institute at VTC, and her research team described the discovery in a paper published Oct. 28 in Nature Communications.

“We don’t always eat because we are hungry and we have certain physical needs,” said Shin, who is also an assistant professor in the Department of Human Nutrition, Foods, and Exercise in Virginia Tech’s College of Agriculture and Life Sciences. “Whenever we get stressed or feel some threat, then it can also trigger our eating motivation. We think this molecule is the culprit.”

Shin and her research team began their study by investigating a small molecule, Proenkephalin. This molecule is common in multiple parts of the brain, but little research had examined its role in the hypothalamus. Shin suspected it played a role in stress and eating because the hypothalamus is a center for regulating eating behavior.

The lab exposed mice to the odor of cat feces. The odor of a natural predator triggered a threat response in the mice, and 24 hours later, the mice exhibited a negative emotional state, overeating behavior, and neurons in their brains showed sensitivity to consumption of high-fat foods.

To confirm the role of the molecule in stress-induced eating, the researchers activated the same neurons artificially with light stimulating a genetically encoded molecule expressed in the neuronal cell’s membrane, without the predator scent, and saw a similar response. In addition, when they exposed the mice to the cat odor and quieted the reaction of the neurons expressing that molecule with the same technique, the mice showed no negative emotional state and didn’t overeat.

“So something about this molecule itself is very critical to inducing overconsumption after the threat,” Shin said.

The discovery points toward a possible target for therapy to alleviate emotionally triggered eating.

“We have much more to learn about this molecule,” Shin said, “but we found its location and it could be a good starting point.”

Shin’s first-authors on the study are In-Jee You, a former research associate at the institute, and Yeeun Bae, a human nutrition, foods, and exercise graduate student working in her lab.

Shin’s research is supported by funding from the National Institutes of Health, the Fralin Biomedical Research Institute Seale Innovation Fund, and the integrated Translational Health Research Institute of Virginia. Shin is a former iTHRIV scholar.

JOURNAL

Nature Communications

DOI

10.1038/s41467-023-42623-6

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state

University of Louisville awarded $11.5 million for research to prevent and treat eating disorders

Grant and Award Announcement

UNIVERSITY OF LOUISVILLE

A University of Louisville researcher has been awarded $11.5 million from the National Institutes of Health (NIH) to better understand and address some of the most devastating effects of eating disorders.

Eating disorders affect an estimated 9% of Americans — nearly 30 million people — and can impact a person’s eating behaviors and perceptions about food and their bodies. The UofL research, backed by three grants, will investigate how eating disorders may develop in childhood and adolescence, their contribution to suicidal behaviors and how innovative personalized treatment may offer hope.

“UofL has made a longstanding commitment to groundbreaking research and discovery that makes a positive impact on our world,” said President Kim Schatzel. “This is research that can save and improve the lives of millions of Americans and many, many more around the world impacted by eating disorders.”

The work is led by researcher Cheri Levinson, who specializes in the study and intervention of eating and anxiety disorders. The key, she said, is a personalized approach to diagnosis and treatment, recognizing that these disorders affect people of all different ages, ethnicities, gender identities and backgrounds, and individualizing treatment to each specific person.

“Despite the high prevalence of these conditions, there are few available treatment and prevention options,” said Levinson, an associate professor in the UofL College of Arts and Sciences and director of the Eating Anxiety Treatment (EAT) Lab. “This work not only will create options, but opens this whole possibility for treatments that are personalized based on the individual. Because eating disorders don’t just affect one kind of person and there are a multitude of different factors that can influence them.”

Through an NIH research project grant totaling nearly $4 million, Levinson’s team will study how eating disorders develop in childhood and beyond, with the hope their findings can help avert the large personal and societal costs associated with childhood onset and chronic disorders. Recent studies show more than one in five kids worldwide may show signs of disordered eating.

A second project grant, also nearly $4 million, will identify patterns of anorexia nervosa — an eating disorder characterized by a fear of gaining weight — that contribute to suicide risk, with data providing a model of personalized psychiatric medicine and new methods of prevention and treatment. Currently, patients with anorexia have a suicide risk 18 times higher than those without an eating disorder.

The third grant, a prestigious NIH Director’s New Innovator Award, also worth nearly $4 million across two phases, will further the creation and dissemination of a novel personalized treatment for eating disorders and integrate social determinants of health (food insecurity, racism) into treatment. The New Innovator Award, part of NIH’s High-Risk, High-Reward Research program, supports unusually innovative research from early-career investigators who are within 10 years of their final degree or clinical residency. Levinson is the first from UofL and the first studying eating disorders to receive this award.

“Our mission at the College of Arts and Sciences is to improve life in the Commonwealth, including by creating new knowledge through groundbreaking research and innovation,” said Dayna Touron, the college’s dean. “Dr. Levinson’s work will undoubtedly improve the lives of millions living with eating disorders, and we are very proud to count her among our faculty.”

These grants are the culmination of years of groundbreaking work by Levinson and her team, for which they earned a UofL Trailblazer Award in early 2023. The research has also received support through UofL’s Office of Research and Innovation, including mentoring through the Ascending Stars Fellows Program for promising mid-career faculty.

Work to develop a companion personalized treatment application and virtual reality technology has also been supported by the office’s Innovation and Commercialization and UofL New Ventures teams. This includes patenting, entrepreneurial coaching and training and financial support through two innovation development programs: KYNETIC, focused on furthering biomedical technologies, and PRePARE, focused on technologies that address a health or societal problem resulting from the COVID-19 pandemic.

“UofL has built a strong and vibrant ecosystem and supports for important research, like this, that can improve and save lives,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “We’re so proud of the work Dr. Levinson and her team are doing and the positive impacts it will have across the U.S. and the globe.”

Fish-like genetic program used to turn human retinal cells into neurons

Peer-Reviewed Publication

INTERNATIONAL SOCIETY FOR STEM CELL RESEARCH

ASCL1 induces neurogenesis in human Muller glia — IMAGE:
“OVERALL, OUR STUDY PROVIDES A PROOF-OF-PRINCIPLE THAT HUMAN GLIA CAN BE REPROGRAMMED TO CELLS THAT ARE CAPABLE OF MAKING NEW NEURONS," SAID THOMAS REH, PHD, UNIVERSITY OF WASHINGTON, USA. "THIS OPENS UP AN ENTIRELY NEW WAY TO REPAIR THE RETINA IN PEOPLE THAT HAVE LOST NEURONS TO DISEASE OR TRAUMA."
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CREDIT: THOMAS REH, PHD

Loss of neurons in in the retina due to trauma or disease leads to vision impairment or blindness, a process which is irreversible in humans. Interestingly, some animals like fish have the built-in ability to regenerate retinal neurons by turning another retinal cell type called “Muller glia” into neurons. This conversion does not happen spontaneously in humans and other mammals, but new research by Thomas Reh, Juliette Wohlschlegel, and colleagues at the University of Washington, USA, published in the journal Stem Cell Reports, shows that human Muller glia can be coaxed into changing identity in the laboratory, which could serve as a potential source of new neurons to treat vision loss.

"Overall, our study provides a proof-of-principle that human glia can be reprogrammed to cells that are capable of making new neurons, said Thomas Reh, PhD, University of Washington. "This opens up an entirely new way to repair the retina in people that have lost neurons to disease or trauma."

Muller glia are supportive cells in the retina which help photoreceptors and other retinal neurons to function properly. In some species like fish and birds, Muller glia turn into immature retinal cells upon injury and subsequently generate new retinal neurons. By contrast, Muller glia in the mammalian retina react to injury with scar formation and inflammation without making new neurons. This difference in behavior is based on different genetic programs being activated in fish versus mammalian Muller glia after injury. Artificial activation of a fish-like genetic program can turn mouse Muller glia into retinal neurons according to prior research. However, up until now, it has not been known if the same strategy can be used to convert human Muller glia into neurons. To answer this question, the researchers genetically modified human Muller glia in the lab to switch on neurons-specific genetic programs, as it naturally happens in fish. Indeed, within a week, the genetically modified cells adopted a neuron-like characteristics resembling immature retinal neurons. These findings suggest that human Muller glia can be coaxed into neurons and may serve as a resource to generate new neurons in patients’ retinas in the future. Of note, Muller glia in this study were derived from immature Muller glia and it remains to be seen if similar approaches can transform adult human Muller glia into neurons, and to what efficiency.

JOURNAL

Stem Cell Reports

DOI

10.1016/j.stemcr.2023.10.021

ARTICLE TITLE

ASCL1 induces neurogenesis in human Muller glia

ARTICLE PUBLICATION DATE

30-Nov-2023