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Lung cancer, the most common cancer worldwide, is targeted with radiation therapy (RT) in nearly one-half of cases. RT planning is a manual, resource-intensive process that can take days to weeks to complete, and even highly trained physicians vary in their determinations of how much tissue to target with radiation. Furthermore, a shortage of radiation-oncology practitioners and clinics worldwide is expected to grow as cancer rates increase. Brigham and Women’s Hospital researchers and collaborators, working under the Artificial Intelligence in Medicine Program of Mass General Brigham, developed and validated a deep learning algorithm that can identify and outline (“segment”) a non-small cell lung cancer (NSCLC) tumor on a computed tomography (CT) scan within seconds. Their research, published in Lancet Digital Health, also demonstrates that radiation oncologists using the algorithm in simulated clinics performed as well as physicians not using the algorithm, while working 65 percent more quickly.
“The biggest translation gap in AI applications to medicine is the failure to study how to use AI to improve human clinicians, and vice versa,” said corresponding author Raymond Mak, MD, of the Brigham’s Department of Radiation Oncology. “We’re studying how to make human-AI partnerships and collaborations that result in better outcomes for patients. The benefits of this approach for patients include greater consistency in segmenting tumors and accelerated times to treatment. The clinician benefits include a reduction in mundane but difficult computer work, which can reduce burnout and increase the time they can spend with patients.”
The researchers used CT images from 787 patients to train their model to distinguish tumors from other tissues. They tested the algorithm’s performance using scans from over 1,300 patients from increasingly external datasets. Developing and validating the algorithm involved close collaboration between data scientists and radiation oncologists. For example, when the researchers observed that the algorithm was incorrectly segmenting CT scans involving the lymph nodes, they retrained the model with more of these scans to improve its performance.
Finally, the researchers asked eight radiation oncologists to perform segmentation tasks as well as rate and edit segmentations produced by either another expert physician or the algorithm (they were not told which). There was no significant difference in performance between human-AI collaborations and human-produced (de novo) segmentations. Intriguingly, physicians worked 65 percent faster and with 32 percent less variation when editing an AI-produced segmentation compared to a manually produced one, even though they were unaware of which one they were editing. They also rated the quality of AI-drawn segmentations more highly than the human expert-drawn segmentations in this blinded study.
Going forward, the researchers plan to combine this work with AI models they designed previously that can identify “organs at risk” of receiving undesired radiation during cancer treatment (such as the heart) and thereby exclude them from radiotherapy. They are continuing to study how physicians interact with AI to ensure that AI-partnerships help, rather than harm, clinical practice, and are developing a second, independent segmentation algorithm that can verify both human and AI-drawn segmentations.
“This study presents a novel evaluation strategy for AI models that emphasizes the importance of human-AI collaboration,” said co-author Hugo Aerts, PhD, of the Department of Radiation Oncology. “This is especially necessary because in silico (computer-modeled) evaluations can give different results than clinical evaluations. Our approach can help pave the way towards clinical deployment.”
This study was funded by the National Institutes of Health (U24CA194354, U01CA190234, and U01CA209414).
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Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

Researchers estimate that half of all high school students in the United States have tried vaping at least once. One third of these students vape regularly. Since e-cigarettes were introduced to the U.S. in 2013, they’ve become more and more popular, especially among teens. From 2019-2020, the popularity of disposable e-cigarette use among U.S. high school students who currently vaped went up by 1,000%, from 2.4% to 26.5%, according to the CDC.
Since nicotine in e-cigarettes is highly addictive, and e-cigarette use in teens leads to higher risks of smoking regular cigarettes later in life, researchers want to know more about which groups of teens are currently vaping and underlying reasons that put them at risk to start.
A study published today in the American Journal of Preventive Medicine used survey data from more than 38,000 U.S. high school students from 2015-2019 to determine how prevalent vaping is in different sexual orientation, race, and ethnicity groups. What they found are dramatic differences in vaping rates across these markers of identity, and sometimes in surprising patterns.
Co-written by Andy Tan, associate professor at the Annenberg School for Communication, and Juhan Lee, a postdoctoral research fellow at the Yale University School of Medicine, the study fills in a wide gap that exists in e-cigarette studies: research on vaping prevalence among young people at the intersections of more than one minoritized identity.
The study uncovered significant differences in the prevalence of current e-cigarette use between lesbian and heterosexual girls when comparing across racial groups.
Current e-cigarette use was higher in Black girls who identify as lesbian compared to Black girls who identify as heterosexual (18.2% versus 7.1%). The rate was also higher in multiracial girls who identify as lesbian compared to multiracial girls who identify as heterosexual (17.9% versus 11.9%). On the other hand, white girls who identify as lesbian were found to be at lower risk of current vaping compared to white girls who identify as heterosexual (9.1% versus 16.1%).
Among boys, there were no significant interactions between sexual orientation and race or ethnicity in relation to vaping prevalence.
Previous surveys of gay and lesbian teens suggest that e-cigarette use might be a coping mechanism to deal with the stress of sexual orientation or gender identity-based discrimination or bullying, or a way to bond with others in their social circle, the authors say. However, prior studies have not reported how e-cigarette use prevalence among youth differ at the intersections of sexual orientation, sex, race, and ethnicity.
One possible reason for finding disparities in e-cigarette use at the intersection of sexual orientation and race among girls, but not boys may be due to higher levels of targeted e-cigarette marketing toward queer women of color, the authors say.
Prior research has found that when compared to white heterosexual young women (aged 18-24), bisexual Black women and bisexual Hispanic women reported higher levels of exposure to ads for tobacco products, while there were no substantial differences in exposure to these ads among young adult men.
“For years, the tobacco industry has targeted marketing toward traditionally marginalized groups, whether in clubs, bars, Pride events, or through magazines,” says Tan, who is also director of the Health Communication & Equity Lab. “Sexual, racial, and ethnic minority youth are more likely to report engaging with online tobacco advertising including e-cigarette ads on social media.”
Tan says he hopes the findings from this study can jumpstart further research and interventions to prevent teen vaping at the intersections of sexual orientation, race, and ethnicity. He is currently leading research to develop and test the effectiveness of anti-vaping campaigns on social media tailored for sexual and gender minority youth.
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Materials provided by University of Pennsylvania. Original written by Hailey Reissman. Note: Content may be edited for style and length.

COVID-19 has had an enormous health impact on societies all over the world. In Denmark, a total of 30,000 healthy years of life were lost as a direct result of the disease, according to calculations of the burden of disease from the DTU National Food Institute and the SSI.
The study measured the direct burden of COVID-19 at the population level, taking into account the number of healthy years lost due to premature mortality and disability due to living with acute symptoms of the disease.
“The estimated burden of disease would be even higher if we had included the long-term effects and indirect costs, such as postponed treatments or mental health problems caused by the lockdown. These figures were not available when the study was carried out,” says senior researcher Sara Monteiro Pires at the DTU National Food institute.
The researchers have used a protocol for calculating the disease burden of COVID-19, which was developed under the auspices of the European Burden of Disease Network. The DTU National Food Institute and the SSI are part of the network.
High mortality among the elderly but low among the young
To estimate the health impact of a disease, researchers used the metric ‘disability adjusted life years’ (DALY), an overall measure of reduced quality of life and premature death. This metric makes it possible to compare how diseases affect populations in relation to e.g. geography, age and mortality.
One pattern that clearly stood out for COVID-19 was a high mortality rate in the 70+ age group and especially among men, while the consequences among the younger part of the population were very small. 447 deaths were registered among the 80-89-year-olds during the period and zero deaths among the 20-29-year-olds.
Important knowledge for authorities
Burden of disease studies provide authorities with comparable estimates of the health impact of various diseases. This is important knowledge to support decisions on e.g., health care spending and which efforts will have the maximum impact.
“The calculations we present here are only based on the first year of the COVID-19 pandemic. In the meantime, vaccines, better treatments, and a higher immunity in the population in general have been developed. We therefore expect that we will be able to see a decrease in the burden of disease when we look at the figures for the second year with COVID-19 ,” says Senior Researcher Steen Ethelberg from SSI.
Researchers in other countries have also used the protocol to calculate the health impact of COVID-19. These data make it possible to compare the burden of disease across countries that calculate the disease burden in the same way.
The data show that disease burden for COVID-19 in Denmark amounted to 520 DALYs per 100,000, while the figures for Germany and the Netherlands were 368 and 1570 per 100,000, respectively.
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Materials provided by Technical University of Denmark. Original written by Charlotte Aagaard Knudsen. Note: Content may be edited for style and length.

Researchers at Baylor College of Medicine and the Broad Institute of MIT and Harvard and clinicians at Washington University in St. Louis have identified biological markers in triple negative breast cancer (TNBC) that are associated with resistance to chemotherapy treatment. The study is published in the journal Cancer Discovery and was funded by the National Cancer Institute’s Clinical Proteomics Tumor Analysis Consortium (CPTAC).
“TNBC is the most difficult to treat form of breast cancer, with standard treatment requiring multiple chemotherapy drugs that unfortunately often fail to cure the patient,” said first and co-corresponding author Dr. Meenakshi Anurag, assistant professor of medicine at the Lester and Sue Smith Breast Center at Baylor. “It is imperative that we develop approaches to predict response so that only effective treatments are given. Furthermore, patients who don’t respond to standard drugs need entirely new treatment approaches. The discovery of therapeutic alternatives will depend on new insights into how TNBC arises.”
The research team used an innovative analytic approach called “microscaled proteogenomics” that they previously developed (Satpathy et al, 2020) to analyze tumor biopsies taken from TNBC patients prior to treatment with carboplatin and docetaxel combination chemotherapy. Data from standard DNA and RNA sequencing approaches were integrated with mass spectrometry-based proteomics and phosphoproteomic analyses to derive more complete molecular portraits of treatment-responsive versus treatment-resistant tumors.
“The proteomic analysis of pretreatment biopsies uniquely revealed metabolic pathways that were associated with resistance to treatment, including fatty acid metabolism,” said Anurag, also a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. When the team considered both proteomics and gene expression data together, they observed that sensitivity to chemotherapy was marked by higher DNA repair signatures, interferon gamma signaling and immune checkpoint components. These data suggest a multi-omics predictor for chemotherapy response is within reach.
The team then conducted analyses that triangulated treatment response, chromosomal deletion or gain and concordant decreases or increases in mRNA and protein expression. This led the team to determine that a deletion on chromosome 19, located in a region called 19q13.31-33, was associated with resistance to chemotherapy treatment. Of the hundreds of genes deleted in this location, expression of the DNA ligase gene LIG1 was one of the mostly consistently suppressed genes at both the mRNA and protein level. In model systems, and in other TNBC data sets, loss of expression and/or deletion of LIG1 was associated with selective carboplatin resistance and poor clinical outcome.
“LIG1 loss was also associated with poor prognosis in other cancer types, showing that this deletion has broader clinical significance,” Anurag said. The researchers are currently working on clinical grade assays to confirm that LIG1 loss can be safely used to direct carboplatin chemotherapy in TNBC.
Dr. Matthew Ellis, a McNair Scholar at Baylor and director of the Lester and Sue Smith Breast Center at the time of this research, and Dr. Steve Carr, senior director of the Proteomics Platform and an institute scientist at Broad, who together orchestrated the analysis, said, “This groundbreaking study clearly reveals the power of combining microscaled proteogenomic analyses with careful clinical research to produce new insights into the nature of cancer.”
LIG1 is a critical component of lagging strand DNA synthesis that connects Okazaki fragments (small DNA segments that must be connected to complete the synthesis reaction). Interestingly, the lagging stand DNA polymerase POLD1 is frequently co-deleted with LIG1, suggesting a multigenic mechanism is in play. Lagging-strand synthesis components are generally considered essential to cellular survival but here reductions in the levels of these enzymes are associated with marked chromosomal instability in multiple cancer types and selective carboplatin resistance in TNBC. Mechanistic studies are underway to determine how the genome is destabilized and how tumors with LIG1 deletion can be more effectively treated.
“This is an exciting result that is a testament to the remarkably close collaboration between patients, oncology care teams and laboratory scientists. In our view, proteogenomic analyses should be routine in clinical trials to discover clinically useful biomarkers, new biological insight and therapeutic hypotheses,” said Dr. Shankha Satpathy, co-corresponding author of the study and senior group leader at in the Proteomics Platform at Broad.
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Materials provided by Baylor College of Medicine. Original written by Molly Chiu. Note: Content may be edited for style and length.

Finnish and French scientists have revealed how the actin cytoskeleton in cells is controlled in an evolutionarily distant, pathogenic Leishmania parasite. The results also provide tools to fight leishmaniasis and trypanosomiasis.
Leishmania are flagellated protozoan parasites that rely on both sandfly and mammalian hosts. Leishmania species cause severe diseases, especially in tropical countries. Due to their peculiar life cycle and their more than one billion years of evolutionary distance from humans, the cell biology of Leishmania parasites exhibits notable differences compared to human cells.
Leishmania parasites have an actin cytoskeleton, which is a complex, dynamic network of filaments composed of a protein called actin. In humans, the actin cytoskeleton mediates many of the processes in the cells, such as migration, morphogenesis and the uptake of nutrients. In Leishmania parasites, the actin cytoskeleton appears to drive nutrient uptake only. Both the Leishmania actin itself and the proteins regulating the actin cytoskeleton of the parasite are very different from those of humans.
A new study carried out at the University of Helsinki, Finland and at Université Paris Cité, CNRS, Institut Jacques Monod, France revealed how the actin cytoskeleton is regulated in the Leishmania major parasite. According to the study, actin filaments of this evolutionarily distant parasite are much more dynamic compared to the actin filaments in human cells. Through determining the atomic structures of parasite actin filaments, the study also reveals the molecular basis of the remarkably rapid turnover of Leishmania actin filaments.
By focusing on the most divergent actin studied so far, this work sheds light on the evolutionary origins of the actin cytoskeleton.
“Our study suggests that the actin filaments of ancient eukaryotes were very dynamic. Through evolution, the actin cytoskeleton became more complex and more involved in a larger number of cellular functions. We propose that this was accompanied by the stabilization of actin filaments and the simultaneous appearance of a wide array of proteins, which accelerate and control the dynamics of actin filaments,” says the lead author of the study, Tommi Kotila, from the University of Helsinki.
The structural differences between the Leishmania parasite and human actins can be also exploited to generate specific inhibitors against parasite actins.
“Currently available anti-leishmanial drugs have toxicity issues, and parasites have developed ways to achieve drug resistance. Thus, we need new and more specific drugs for treating leishmaniasis, and compounds against actin could be good candidates,” says Academy Professor Pekka Lappalainen from the University of Helsinki.
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Materials provided by University of Helsinki. Note: Content may be edited for style and length.

In the war against cancer, one of the most critical battles is waged on a cellular level as T cells from the immune system are altered in the lab to attack cancer cells. This form of immunotherapy, called chimeric antigen receptor (CAR) T-cell therapy, can be a life-saving treatment resulting in tumor control lasting ten years or longer.
Now an engineer at the University of Houston has found a way to determine which patients are likely to respond to CAR T-cell therapy, saving precious time in treating lymphoma, which is most responsive to this form of immunotherapy. It’s valuable knowledge to have since not all patients respond to the therapy, and some experience severe side effects.
To determine the best patient prospects, Navin Varadarajan, M.D. Anderson Professor of chemical and biomolecular engineering, studied the dynamic interactions between T cells and tumor cells. His findings, reported in the Journal of Clinical Investigation, point to the relationship between a ligand molecule on a cancer cell (CD58) and a protein on a T cell (CD2) which work together to communicate and activate the CD2, turning it into a cancer cell killer.
“The ligand for CD2, CD58 is expressed at higher levels in the tumors of lymphoma patients who respond better to CAR T-cell treatment. We identified that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing,” reports Varadarajan.
Varadarajan and his partners at The University of Texas MD Anderson Cancer Center profiled the dynamic interactions between T cells that comprise patient infusion products and tumors, using the TIMING (Timelapse Imaging Microscopy In Nanowell Grids) method, developed in Varadarajan’s lab at UH. TIMING is high-throughput single-cell technology that merges artificial intelligence with a nanowell imaging platform to simultaneously evaluate how individual cells move, activate, interact, kill and survive.
By interrogating thousands of individual interactions between T cells and tumor cells, the research team identified the important interaction between CD2 and CD58. To translate the results back to the clinic, Varadarajan and Dr. Sattva Neelapu from MD Anderson, stained the tumors obtained before initiation of treatment. That’s how the group was able to show that patients whose tumors expressed CD58 are much more likely to respond to CAR T cell therapy compared to patients whose tumors did not express CD58.
Growing and incubating at Technology Bridge
The University of Houston has obtained a patent on the TIMING process and Varadarajan co-founded the company, CellChorus, to commercialize it. CellChorus is housed at the UH Technology Bridge, which provides space to startup and spin out companies from UH and nurtures their growth.
“We are so lucky to have the Technology Bridge as our incubator space in Houston, near the greatest medical center in the country, with unique access to the centers of medicine difficult to replicate in most other places in the country,” said Varadarajan.
Currently, CellChorus receives target cells from customers and conducts TIMING tests, providing comprehensive dynamic analysis of single cells. Eventually they will be able to send the technology to clinicians, in a piece of equipment like a box so they can perform their own assessments.
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Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

It’s a figure that stands out. Black women have a 36% higher breast cancer mortality rate than other races in spite of having a similar incidence to White women. Black women also are both more likely to be diagnosed with breast cancer at a younger age than White women and have double the rate of the aggressive, harder-to-treat triple negative breast cancer.
There’s ongoing debate about how much of these disparities is due to social determinants of health, such as access to health care, and how much is caused by biology, notes MUSC Hollings Cancer Center researcher Peggi Angel, Ph.D. One hypothesis is that chronic social and economic stressors result in ancestry-dependent molecular changes that create a tumor permissive tissue microenvironment in normal breast tissue, she said, citing findings of her team’s recent study published in Frontiers in Oncology
Angel, an analytical chemist by training, is interested in what’s happening at the molecular level. Her recent study with her graduate student Denys Rujchanarong looked at normal breast tissue tagged as at-risk for breast cancer, according to the Gail Model, which assigns an estimated risk of breast cancer based on personal factors, such as age, the age at start of menstruation and age at birth of first child, and saw associations between socioeconomic stressors and specific N-glycosylation patterns in Black and White women.
N-glycosylation is a metabolic process of creating a sugar modification on a protein structure. The research was an initial step toward linking molecular markers to socioeconomic stress, Angel said.
“We tried to look at differences in social status among Black women and White women and compare that to molecular factors that might be predictive,” she said. “I think this is such a needed area of research because it is really complicated, and there’s clearly some molecular changes that could be linked to geographical origin.”
She noted that it’s important to start looking at differences in breast tissue before cancer arises.

Older adults who participate weekly in many different types of leisure time activities, such as walking for exercise, jogging, swimming laps, or playing tennis, may have a lower risk of death from any cause, as well as death from cardiovascular disease and cancer, according to a new study led by researchers at the National Cancer Institute, part of the National Institutes of Health.
The findings suggest that it’s important for older adults to engage in leisure time activities that they enjoy and can sustain, because many types of these activities may lower the risk of death, the authors wrote.
The findings appear August 24 in JAMA Network Open.
Using data from 272,550 adults between the ages of 59 and 82 who had completed questionnaires about their leisure-time activities as part of the NIH-AARP Diet and Health Study, the researchers looked at whether participating in equivalent amounts of seven different exercise and recreational activities — including running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise — was associated with lowered risk of death.
The researchers found that achieving the recommended amount of physical activity per week through any combination of these activities was associated with a 13% lower risk of death from any cause compared with no participation in these activities. When they looked at the role of each activity individually, playing racquet sports was associated with a 16% reduction in risk and running with a 15% reduction. However, all the activities investigated were similarly associated with lower risks of death.
The second edition of the Physical Activity Guidelines for Americans recommends that adults engage in 2.5 to 5 hours of moderate-intensity aerobic physical activity, or 1.25 to 2.5 hours of vigorous-intensity aerobic physical activity, each week.
The levels of activity by the most active individuals (those who exceeded the recommended levels of physical activity) were associated with even greater reductions in the risk of death, but there were diminishing returns as activity levels increased. Even people who did some recreational activity, though less than the recommended amount, had a 5% reduction in risk of death than those who did not participate in any of the activities studied.
These activities were also associated with a lower risk of death from cardiovascular disease and cancer. Playing racquet sports was associated with the greatest reduction in risk of cardiovascular deaths (27% reduction), while running was associated with the greatest reduction in risk of cancer deaths (19% reduction).
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Materials provided by NIH/National Cancer Institute. Note: Content may be edited for style and length.

Researchers at Washington University School of Medicine in St. Louis have found a new druggable pathway that potentially could be used to help prevent Alzheimer’s dementia.
Amyloid beta accumulation in the brain is the first step in the development of Alzheimer’s dementia. Scientists have poured countless hours and millions of dollars into finding ways to clear amyloid away before cognitive symptoms arise, with largely disappointing results.
In this study, published Aug. 24 in the journal Brain, researchers found a way to increase clearance of waste products from the brains of mice by ramping up a genetic quirk known as readthrough. This same strategy also may be effective for other neurodegenerative diseases characterized by the buildup of toxic proteins, such as Parkinson’s disease, the researchers said.
Every once in a while, the brain protein aquaporin 4 is synthesized with an extra little tail on the end. At first, Darshan Sapkota, PhD — who led this study while a postdoctoral researcher at Washington University but is now an assistant professor of biological sciences at the University of Texas, Dallas — thought this tail represented nothing more than an occasional failure of quality control in the protein-manufacturing process.
“We were studying this very wonky basic science question — ‘How do proteins get made?’ — and we noticed this funny thing,” said senior author Joseph D. Dougherty, PhD, a Washington University professor of genetics and of psychiatry, and Sapkota’s former mentor. “Sometimes the protein-synthesizing machinery blew right through the stop sign at the end and made this extra bit on the end of aquaporin 4. At first, we thought it couldn’t possibly be relevant. But then we looked at the gene sequence, and it was conserved across species. And it had this really striking pattern in the brain: It was only in structures that are important for waste clearance. So that’s when we got excited.”
Scientists already knew that the cell’s protein-building machinery occasionally fails to stop where it should. When the machinery doesn’t stop — a phenomenon known as readthrough — it creates extended forms of proteins that sometimes function differently than the regular forms.

Two doses of psilocybin, a compound found in psychedelic mushrooms, reduces heavy drinking by 83% on average among heavy drinkers when combined with psychotherapy, a new study shows.
Led by researchers at NYU Grossman School of Medicine, the investigation involved 93 men and women with alcohol dependence. They were randomly assigned to receive either two doses of psilocybin or an antihistamine placebo. Neither the researchers nor the study participants knew which medication they received. Within an eight-month period from the start of their treatment, those who were given psilocybin reduced heavy drinking by 83% relative to their drinking before the study began. Meanwhile, those who had received antihistamine reduced their drinking by 51%.
Among the other key findings, the study showed that eight months after their first dose, almost half (48%) of those who received psilocybin stopped drinking altogether compared with 24% of the placebo group.
“Our findings strongly suggest that psilocybin therapy is a promising means of treating alcohol use disorder, a complex disease that has proven notoriously difficult to manage,” says study senior author and psychiatrist Michael Bogenschutz, MD, director of the NYU Langone Center for Psychedelic Medicine.
The U.S. Centers for Disease Control and Prevention reports that excessive alcohol use kills roughly 95,000 Americans every year, often due to binge drinking or liver disease. It is also linked to enormous economic and workplace losses, injury accidents, and impaired learning, memory, and mental health, says Bogenschutz, also a professor in the Department of Psychiatry at NYU Langone Health. Current methods to prevent excessive alcohol use and dependency include psychological counseling, supervised detoxification programs, and certain drug regimens that dampen cravings.
According to study investigators, previous research had already identified psilocybin treatment as an effective means of alleviating anxiety and depression in people with the most severe forms of cancer. And earlier research by Bogenschutz and others suggested that psilocybin could serve as a potential therapy for alcohol use disorder and other addictions.