Wednesday, December 06, 2023

 

Structural racism and lung cancer risk

JAMA Oncology

Peer-Reviewed Publication

JAMA NETWORK




About The Study: The findings of this study suggest that structural racism must be considered as a fundamental contributor to the unequal distribution of lung cancer risk factors and thus disparate lung cancer risk across different racial and ethnic groups. Additional research is needed to better identify mechanisms contributing to inequitable lung cancer risk and tailor preventive interventions. 

Authors: Sidra N. Bonner, M.D., M.P.H., M.Sc., of the University of Michigan in Ann Arbor, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/  

(doi:10.1001/jamaoncol.2023.4897)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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AI model predicts breast cancer risk without racial bias



Reports and Proceedings

RADIOLOGICAL SOCIETY OF NORTH AMERICA

Abnormal Mammogram 

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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

Abnormal Mammogram 

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ABNORMAL MAMMOGRAM.

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CREDIT: RSNA/RADIOLOGY




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.

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 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.

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 

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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.

 

 

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

Football - A Woman's Game 

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AN EVENT SHOWCASING THE LATEST SCIENTIFIC RESEARCH AND BEST PRACTICES IN WOMEN’S FOOTBALL TAKES PLACE AT STAFFORDSHIRE UNIVERSITY ON 11 DECEMBER.

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CREDIT: 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.”

 

 

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.”