Posts Tagged ‘science’

by EMILY MAKOWSKI

Plants pollinated by nectar-drinking bats often have flowers that reflect ultrasonic waves, making it easier for the animals to locate flowers through echolocation. But one cactus does the opposite—it absorbs more ultrasound in the area surrounding its flowers, making them stand out against a “quieter” background, according to a preprint published on bioRxiv last month.

Espostoa frutescens is a type of column-shaped cactus found only in the Ecuadorian Andes mountains. It has small flowers on its side that open at night, attracting bats as they fly from flower to flower in search of nectar. One of its main pollinators is Geoffroy’s tailless bat (Anoura geoffroyi).

“Bats are really good pollinators,” Ralph Simon, a postdoc in Wouter Halfwerk’s lab at Vrije Universiteit Amsterdam and the lead author of the preprint, tells The Scientist. “They carry a lot of pollen in their fur, and they have a huge home range so they can transport pollen from plants that grow far apart. For plants with a patchy distribution pattern like this cactus, it’s especially beneficial to rely on bats for pollination,” he says.

For bats to find the flowers at night, they use echolocation, emitting ultrasonic calls too high for humans to hear that bounce off objects and allow the bats to form a mental map of their surroundings. Some plants have evolved techniques that take advantage of this sonar system and allow bats to better detect flowers, such as making their petals more concave, forming a more reflective surface that can bounce more echolocation back to the bat. But E. frutescens takes a different approach.

Each of E. frutescens’s flowers are surrounded by an area of wooly hairs called the cephalium. Simon and colleagues knew from past measurements that the hairs were sound-absorbent, and were interested in seeing whether this part of the cactus could be involved in helping bats find the flowers. They attached a microphone and speaker to a device resembling the shape and size of a bat head in order to mimic a bat, and played prerecorded echolocation calls to the cacti and measured how much sound was reflected back to the bat replica.

The team found that the hairy cephalium absorbed ultrasound, and that the greatest absorption occurred above 90 kHz, in the range of the frequency of Geoffroy’s tailless bat’s echolocation call. The sound that bounced back to the microphone from the cephalium area was about 14 decibels quieter than the sound that bounced off the non-hairy part of the cacti.

It’s a “totally different mechanism” than the reflection method other cacti use, says Simon. “Instead of making the flowers conspicuous, it dampens the background. The background absorbs the ultrasound, and the flowers show up in [the middle of] this absorbent fur.”

This mechanism makes sense from a communication standpoint, writes May Dixon, a graduate student studying bat behavior in Mike Ryan’s lab at the University of Texas at Austin who was not involved with the study, in an email to The Scientist. “If you are trying to send a message, you have to think not only about the message itself but also the context. For example, if you are calling someone, you should be loud enough for them to hear, sure, but you should also call from a quiet place,” she says.

“There is something wonderful about the ways that plants have found to communicate with animals through evolution,” Dixon notes. “A cactus has no sense of what it is to be a bat—it can’t see, smell, or echolocate—but here it is, sending a bat a message in a language that a bat can understand.”

The cephalium appears to have originally evolved to protect flowers from environmental stressors such as UV rays, drying out, getting too cold, or being eaten, but “during evolution, it co-opted another function, and it functions as a sound absorbing structure as well,” says Simon. The evolution of this mechanism benefits both cactus and bat. “From the bat point of view, with this mechanism, they save time. And for them, it’s important to save time, because they have to visit several hundred flowers each night to get enough energy,” he says.

The current study did not look at whether sites on the plants with the highest sound absorption in the bats’ echolocation range “indeed resulted in the highest detection and visitation rates by bats,” says Jan Komdeur, an evolutionary ecologist at University of Groningen in the Netherlands who did not participate in the research, in an email to The Scientist. In the future, researchers could investigate how often real-life bats approach hairy versus experimentally manipulated hairless flowers, he suggests.

Jorge Schondube, an ecologist at the Universidad Nacional Autónoma de México who was not involved with the study, agrees that research on real-life bats is needed. “The pattern’s very clear, but now [researchers] need to show how the mechanism is actually changing the behavior of the bats,” he says.

Still, he’s impressed by the findings so far. “Nature is very creative. And by being creative, it allows the origin of completely new and unimaginable things. It’s really surprising that something like this can happen, and the paper shows it really, really beautifully. . . . What we’re seeing here is something that has not been seen before in terms of sound.”

https://www.the-scientist.com/news-opinion/ecuadorian-cactus-absorbs-ultrasound–enticing-bats-to-flowers-66981?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=82166272&_hsenc=p2ANqtz-9in3Tqjl731fVW0JE_k3Ht2NOEvCOnql7E5ADhmEp4j43Rrs5Q6gxTipSPvHXAs-8C6MvOvVFdBpktnFeyya1pvZPF2A&_hsmi=82166272


Dr. Moir’s radical and iconoclastic theories defied conventional views of the disease. But some scientists were ultimately won over.

By Gina Kolata

Robert D. Moir, a Harvard scientist whose radical theories of the brain plaques in Alzheimer’s defied conventional views of the disease, but whose research ultimately led to important proposals for how to treat it, died on Friday at a hospice in Milton, Mass. He was 58.

His wife, Julie Alperen, said the cause was glioblastoma, a type of brain cancer.

Dr. Moir, who grew up on a farm in Donnybrook, a small town in Western Australia, had a track record for confounding expectations. He did not learn to read or write until he was nearly 12; Ms. Alperen said he had told her that the teacher at his one-room schoolhouse was “a demented nun.” Yet, she said, he also knew from age 7 that he wanted to be a scientist.

Dr. Moir succeeded in becoming a researcher who was modest and careful, said his Ph.D. adviser, Dr. Colin Masters, a neuropathologist at the University of Melbourne. So Dr. Masters was surprised when Dr. Moir began publishing papers proposing an iconoclastic rethinking of the pathology of Alzheimer’s disease.

Dr. Moir’s hypothesis “was and is a really novel and controversial idea that he alone developed,” Dr. Masters said.

“I never expected this to come from this quiet achiever,” he said.

Dr. Moir’s theory involved the protein beta amyloid, which forms plaques in the brains of Alzheimer’s patients.

Conventional wisdom held that beta amyloid accumulation was a central part of the disease, and that clearing the brain of beta amyloid would be a good thing for patients.

Dr. Moir proposed instead that beta amyloid is there for a reason: It is the way the brain defends itself against infections. Beta amyloid, he said, forms a sticky web that can trap microbes. The problem is that sometimes the brain goes overboard producing it, and when that happens the brain is damaged.

The implication is that treatments designed to clear the brain of amyloid could be detrimental. The goal would be to remove some of the sticky substance, but not all of it.

The idea, which Dr. Moir first proposed 12 years ago, was met with skepticism. But he kept at it, producing a string of papers with findings that supported the hypothesis. Increasingly, some of the doubters have been won over, said Rudolph Tanzi, a close friend and fellow Alzheimer’s researcher at Harvard.

Dr. Moir’s unconventional ideas made it difficult for him to get federal grants. Nearly every time he submitted a grant proposal to the National Institutes of Health, Dr. Tanzi said in a phone interview, two out of three reviewers would be enthusiastic, while a third would simply not believe it. The proposal would not be funded.

But Dr. Moir took those rejections in stride.

“He’d make a joke about it,” Dr. Tanzi said. “He never got angry. I never saw Rob angry in my life. He’d say, ‘What do we have to do next?’ He was always upbeat, always optimistic.”

Dr. Moir was supported by the Cure Alzheimer’s Fund, and he eventually secured some N.I.H. grants.

Dr. Moir first came to the United States in 1994, when Dr. Tanzi was looking for an Alzheimer’s biochemist to work in his lab. Working with the lab as a postdoctoral fellow and later as a faculty member with his own lab, Dr. Moir made a string of major discoveries about Alzheimer’s disease.

For example, Dr. Moir and Dr. Tanzi found that people naturally make antibodies to specific forms of amyloid. These antibodies protect the brain from Alzheimer’s but do not wipe out amyloid completely. The more antibodies a person makes, the greater the protection against Alzheimer’s.

That finding, Dr. Tanzi said, inspired the development of an experimental drug, which its manufacturer, Biogen, says is helping to treat some people with Alzheimer’s disease. Biogen plans to file for approval from the Food and Drug Administration.

Robert David Moir was born on April 2, 1961, in Kojonup, Australia, to Mary and Terrence Moir, who were farmers. He studied the biochemistry of Alzheimer’s disease at the University of Western Australia before joining Dr. Tanzi’s lab.

Once he learned to read, Ms. Alperen said, he never stopped — he read science fiction, the British magazine New Scientist and even PubMed, the federal database of scientific publications.

“Rob had an encyclopedic knowledge of the natural world,” she said.

He shared that love with his family, on frequent hikes and on trips with his young children to look for rocks, insects and fossils. He also played Australian-rules football, which has elements of rugby as well as American football, and helped form the Boston Demons Australian Rules Football Team in 1997, his wife said.

In addition to his wife, with whom he lived in Sharon, Mass., Dr. Moir’s survivors include three children, Alexander, Maxwell and Holly Moir; a brother, Andrew; and a sister, Catherine Moir. His marriage to Elena Vaillancourt ended in divorce.

Even on land, crocodiles are no fish out of water. While these reptiles might look lazy and slow sunning on the bank, they can easily pick up speed when necessary, and a scary number can gallop or bound like a horse or a dog.

Bounding is when an animal’s forelimbs hit the ground at the same time, with the back legs pushing off soon after; meanwhile, a gallop is a four-beat sequence whereby the fore and hindlimbs take turns landing.

Freshwater crocodiles from Australia (Crocodylus johnstoni) were historically thought to be the only species capable of doing both. But that’s not actually true. Not even close.

It turns out even scientists have underestimated these creatures. Past research suggested only a handful of croc species were able to gallop, but a new study now adds five more to the mix, suggesting it’s a whole lot more common than we ever thought.

Setting up video cameras around a zoological park in Florida, veterinary scientists analysed the gaits and speeds of 42 individuals from 15 species of crocodylia, which includes true crocodiles (family Crocodylidae), alligators and caimans.

While alligators and caimans were only able to trot on land, the team noticed eight species of crocodile capable of galloping or bounding.

They claim their study is the first to properly document galloping in the Philippine crocodile (Crocodylus mindorensis), the Cuban crocodile (C. rhombifer), the American crocodile (C. acutus), the West-African slender-snouted crocodile (Mecistops cataphractus) and the dwarf crocodile (Osteolaemus tetraspis).

Judging by how common this skill appears to be, there might even be more species that can do the same. There have already been anecdotal reports of galloping in species such as the marsh crocodile (C. palustris) and the New Guinea crocodile (C. novaeguineae).

“We were really surprised at one major thing – despite the different gaits crocodiles and alligators use, they all can run about as fast,” John Hutchinson, a specialist in evolutionary biomechanics at the Royal Veterinary College (RVC), told PA.

No matter what their size, almost every species studied was able to reach nearly 18 kilometres per hour (11 mph), whether it be through trotting, galloping or bounding.

Only crocodiles, however, could use their legs asymmetrically, providing longer stride frequencies, especially among those with smaller body sizes. Why alligators cannot do this remains uncertain, but the researchers think this skill is probably ancestral and has less to do with speed than we thought.

“We suspect that bounding and galloping give small crocodiles better acceleration and manoeuvrability, especially useful for escaping from danger,” explains Hutchinson

“It seems like alligators and caiman stand their ground rather than run away with an extreme gait.”

Similar to other studies, the researchers think the crocodile’s unusual asymmetrical gait came from a long-lost ancestor that lived on the land and had longer legs.

If this is right, it could mean that the ancestors of the alligators somehow lost this ability or no longer express it.

But there’s also another possibility that is rarely acknowledged: the common ancestor of today’s 20 crocodile species may have actually evolved this asymmetrical gait as opposed to inheriting it.

Looking at related species could clear up some of the confusion – the gharial is an Asian fish-eating crocodile that lies outside the Crocodyloidea  and Alligatoroidea ancestry, so if they can be shown to have asymmetrical gaits, it could shed light on how this skill appeared.

But similar to crocodiles and alligators, the gaits of the gharial’s are not well documented, so there’s clearly a lot more research that needs to be done.

“Together, our new observations of asymmetrical gaits and our broader dataset on locomotor kinematics spanning the clade Crocodylia considerably expand our knowledge of their behaviours and natural history,” the authors conclude.

“Importantly, this combined evidence strongly refutes the popular notion that only a few crocodiles use asymmetrical gaits.”

The study was published in Scientific Reports.

https://www.sciencealert.com/approach-with-caution-more-crocodile-species-than-we-thought-can-reach-a-gallop

White House officials are working on an executive order that would boost public access to federally funded research, prompting publishers to panic about the future of their business models, according to people familiar with the plan.

Ostensibly, the order would follow longtime bipartisan interest in improving public access to research that is paid for by taxpayers.

It is expected to require that publicly funded science be obtainable for free immediately, building on an Obama initiative, multiple sources said.

A memo adopted in 2013 mandated that the results of such research be made available within one year of publication.

Though there is generally broad support for public access, publishing groups like the Association of American Publishers worry that a tougher order would upend their subscription-based business model.

Once it caught wind of the effort, AAP began drafting a sharply worded letter of concern to the White House, multiple sources said. The letter could be sent as early as tomorrow.

About a dozen sources told E&E News that they were aware the White House has been considering an executive order but the details remain murky. A senior administration official declined to comment on “internal deliberative processes that may or may not be happening.”

“President Trump’s Administration continues to be focused on scientific discovery and economic expansion,” the official added via email.

Michael Stebbins, who helped draft the Obama-era memo, generally expressed support for public access and noted that it could spur innovation. “But the devil is definitely in the details,” he said.

Many academic journals are funded by subscription fees collected in the first year of publication. The Trump mandate could force publishers to shift their model so authors pay hefty article processing charges, or APCs.

“Here’s the challenge: A world in which there is immediate open access will result in serious pain to a scientific society or small publisher who relies on subscription revenue,” Stebbins added. “That revenue will have to be made up somehow for them to survive.”

Some scientific experts, who are generally skeptical of the Trump team, are worried that the initiative parallels what they call the administration’s incessant attack on science and, by extension, provides favors to industry.

“What problem are we trying to solve?” asked Andrew Rosenberg, an advocate with the Union of Concerned Scientists.

Others noted that the order would give international competitors like China access to American research, which has been a concern of the Trump administration.

It’s also unusual, sources noted, that a Republican administration would adopt policies that could seriously affect business models.

Impacts to publishers could vary. A spokeswoman for the American Association for the Advancement of Science had no direct comment on the administration’s reported plans but obliquely expressed concerns about the potential financial impact.

The nonprofit association publishes a half-dozen journals. One offers immediate free access to its articles, and the other five allow open access to peer-reviewed articles after a year for registered users, the spokeswoman, Tiffany Lohwater, said in an email this week. Articles in those five journals are also available for free as soon as they are posted in university archives technically known as “institutional repositories.”

“High-quality scientific publishing, as AAAS does, requires considerable resource investment, including to identify the papers that have the potential to significantly impact the pace of science,” she said.

George Allen, chief scientist with Northeast States for Coordinated Air Use Management, a Boston-based consortium of air pollution agencies, did not doubt the Trump order would get huge pushback from publishers.

“If you completely take away their business model, then they have no incentive to exist,” he said. He thought allowing free access after a year would be “a reasonable compromise

https://www.eenews.net/stories/1061836761


This piglet had some cells from a monkey but died within a week of birth
Tang Hai

By Michael Le Page

Pig-primate chimeras have been born live for the first time but died within a week. The two piglets, created by a team in China, looked normal although a small proportion of their cells were derived from cynomolgus monkeys.

“This is the first report of full-term pig-monkey chimeras,” says Tang Hai at the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing.

The ultimate aim of the work is to grow human organs in animals for transplantation. But the results show there is still a long way to go to achieve this, the team says.

Hai and his colleagues genetically modified cynomolgus monkey cells growing in culture so they produced a fluorescent protein called GFP. This enabled the researchers to track the cells and their descendents. They then derived embryonic stem cells from the modified cells and injected them into pig embryos five days after fertilisation.

More than 4000 embryos were implanted in sows. Ten piglets were born as a result, of which two were chimeras. All died within a week. In the chimeric piglets, multiple tissues – including in the heart, liver, spleen, lung and skin – partly consisted of monkey cells, but the proportion was low: between one in 1000 and one in 10,000.

It is unclear why the piglets died, says Hai, but because the non-chimeric pigs died as well, the team suspects it is to do with the IVF process rather than the chimerism. IVF doesn’t work nearly as well in pigs as it does in humans and some other animals.

The team is now trying to create healthy animals with a higher proportion of monkey cells, says Hai. If that is successful, the next step would be to try to create pigs in which one organ is composed almost entirely of primate cells.

Something like this has already been achieved in rodents. In 2010, Hiromitsu Nakauchi, now at Stanford University in California, created mice with rat pancreases by genetically modifying the mice so their own cells couldn’t develop into a pancreas.

Pig-human chimeras

In 2017, Juan Carlos Izpisua Belmonte’s team at the Salk Institute in California created pig-human chimeras, but only around one in 100,000 cells were human and, for ethical reasons, the embryos were only allowed to develop for a month. The concern is that a chimera’s brain could be partly human.

This is why Hai and his team used monkey rather than human cells. But while the proportion of monkey cells in their chimeras is higher than the proportion of human cells in Belmonte’s chimeras, it is still very low.

“Given the extremely low chimeric efficiency and the deaths of all the animals, I actually see this as fairly discouraging,” says stem cell biologist Paul Knoepfler at the University of California, Davis.

He isn’t convinced that it will ever be possible to grow organs suitable for transplantation by creating animal-human chimeras. However, it makes sense to continue researching this approach along with others such as tissue engineering, he says.

According to a July report in the Spanish newspaper El País, Belmonte’s team has now created human-monkey chimeras, in work carried out in China. The results have not yet been published.

While interspecies chimerism doesn’t occur naturally, the bodies of animals including people can consist of a mix of cells. Mothers have cells from their children growing in many of their organs, for instance, a phenomenon called microchimerism.

Journal reference: Protein & Cell, DOI: 10.1007/s13238-019-00676-8

Read more: https://www.newscientist.com/article/2226490-exclusive-two-pigs-engineered-to-have-monkey-cells-born-in-china/#ixzz67RYaU5XS

by David Nield

Scientists researching a key aspect of biochemistry in living creatures have been taking a very close look at the tiny Caenorhabditis elegans roundworm. Their latest results show that when these nematodes get put under more biochemical stress early in their lives, they somehow tend to live longer.

This type of stress, called oxidative stress – an imbalance of oxygen-containing molecules that can result in cellular and tissue damage – seems to better prepare the worms for the strains of later life, along the same lines as the old adage that whatever doesn’t kill you, makes you stronger.

You might think that worm lifespans have no bearing on human life. And surely, until we have loads more research done in this field, it would be a big leap to say the same principles of prolonging one’s lifespan might hold true for human beings.

But there’s good reason to put C. elegans through the paces. This model organism has proven immensely helpful for researchers trying to better understand key biological functions present in worm and human alike – and oxidative stress is one such function.

The little wriggly creatures are known to have significant variations in their lifespan even when the whole population is genetically identical and grows up in the exact same conditions. So the team went looking for other factors that affect C. elegans’ longevity.

“The general idea that early life events have such profound, positive effects later in life is truly fascinating,” says biochemist Ursula Jakob from the University of Michigan.

Jakob and her colleagues sorted thousands of C. elegans larvae based on the oxidative stress levels they experienced during development – this stress arises when cells produce more oxidants and free radicals than they can handle. It’s a normal part of the ageing process, but it’s also triggered by exercise and a limited food supply.

One way to measure this stress is by the levels of reactive oxygen species (ROS) molecules an organism produces – simply put, this measurement indicates the biochemical stress an organism is under. In the case of these roundworms, the more ROS were produced during development, the longer their lifespans turned out to be.

To explain how this effect of ROS might come about, the researchers went looking for changes in the worms’ genetic regulation, specifically those genes that are known to be involved in dealing with oxidative stress.

While doing so, they detected a key difference – the nematodes exposed to more ROS during development appeared to have undergone an epigenetic change (a gene expression switch that can happen due to environmental influences) that increased the oxidative stress resistance of their body’s cells.

There are still a lot of questions to answer, but the researchers think their results identify one of the stochastic – or random – influences on the lifespan of organisms; it’s something that has been hypothesised in the field of the genetics of ageing. And down the line, it may turn out to be relevant for ageing humans, too.

“This study provides a foundation for future work in mammals, in which very early and transient metabolic events in life seem to have equally profound impacts on lifespan,” the researchers conclude.

The study has been published in Nature.

https://www.sciencealert.com/biological-stress-in-early-life-could-be-one-of-the-keys-to-a-long-lifespan?perpetual=yes&limitstart=1


Case Western Reserve researchers use AI with routine CT scans to predict how well lung cancer patients will respond to expensive treatment based off changes in texture patterns inside and outside the tumor.

Scientists from the Case Western Reserve University digital imaging lab, already pioneering the use of artificial intelligence (AI) to predict whether chemotherapy will be successful, can now determine which lung-cancer patients will benefit from expensive immunotherapy.

And, once again, they’re doing it by teaching a computer to find previously unseen changes in patterns in CT scans taken when the lung cancer is first diagnosed compared to scans taken after the first two to three cycles of immunotherapy treatment. And, as with previous work, those changes have been discovered both inside—and outside—the tumor, a signature of the lab’s recent research.

“This is no flash in the pan—this research really seems to be reflecting something about the very biology of the disease, about which is the more aggressive phenotype, and that’s information oncologists do not currently have,” said Anant Madabhushi, whose Center for Computational Imaging and Personalized Diagnostics (CCIPD) has become a global leader in the detection, diagnosis and characterization of various cancers and other diseases by meshing medical imaging, machine learning and AI.

Currently, only about 20% of all cancer patients will actually benefit from immunotherapy, a treatment that differs from chemotherapy in that it uses drugs to help your immune system fight cancer, while chemotherapy uses drugs to directly kill cancer cells, according to the National Cancer Institute.

Madabhushi said the recent work by his lab would help oncologists know which patients would actually benefit from the therapy, and who would not.

“Even though immunotherapy has changed the entire ecosystem of cancer, it also remains extremely expensive—about $200,000 per patient, per year,” Madabhushi said. “That’s part of the financial toxicity that comes along with cancer and results in about 42% of all new diagnosed cancer patients losing their life savings within a year of diagnosis.”

Having a tool based on the research being done now by his lab would go a long way toward “doing a better job of matching up which patients will respond to immunotherapy instead of throwing $800,000 down the drain,” he added, referencing the four patients out of five who will not benefit, multiplied by annual estimated cost.

Case Western Reserve researchers use AI with routine CT scans to predict how well lung cancer patients will respond to expensive treatment based off changes in texture patterns inside and outside the tumor
Scientists from the Case Western Reserve University digital imaging lab, already pioneering the use of artificial intelligence (AI) to predict whether chemotherapy will be successful, can now determine which lung-cancer patients will benefit from expensive immunotherapy.

And, once again, they’re doing it by teaching a computer to find previously unseen changes in patterns in CT scans taken when the lung cancer is first diagnosed compared to scans taken after the first two to three cycles of immunotherapy treatment. And, as with previous work, those changes have been discovered both inside—and outside—the tumor, a signature of the lab’s recent research.

“This is no flash in the pan—this research really seems to be reflecting something about the very biology of the disease, about which is the more aggressive phenotype, and that’s information oncologists do not currently have,” said Anant Madabhushi, whose Center for Computational Imaging and Personalized Diagnostics (CCIPD) has become a global leader in the detection, diagnosis and characterization of various cancers and other diseases by meshing medical imaging, machine learning and AI.

Currently, only about 20% of all cancer patients will actually benefit from immunotherapy, a treatment that differs from chemotherapy in that it uses drugs to help your immune system fight cancer, while chemotherapy uses drugs to directly kill cancer cells, according to the National Cancer Institute.

Madabhushi said the recent work by his lab would help oncologists know which patients would actually benefit from the therapy, and who would not.

“Even though immunotherapy has changed the entire ecosystem of cancer, it also remains extremely expensive—about $200,000 per patient, per year,” Madabhushi said. “That’s part of the financial toxicity that comes along with cancer and results in about 42% of all new diagnosed cancer patients losing their life savings within a year of diagnosis.”

Having a tool based on the research being done now by his lab would go a long way toward “doing a better job of matching up which patients will respond to immunotherapy instead of throwing $800,000 down the drain,” he added, referencing the four patients out of five who will not benefit, multiplied by annual estimated cost.

New research published
The figure above shows differences in CT radiomic patterns before and after initiation of checkpoint inhibitor therapy.

The new research, led by co-authors Mohammadhadi Khorrami and Prateek Prasanna, along with Madabhushi and 10 other collaborators from six different institutions was published in November in the journal Cancer Immunology Research.

Khorrami, a graduate student working at the CCIPD, said one of the more significant advances in the research was the ability of the computer program to note the changes in texture, volume and shape of a given lesion, not just its size.

“This is important because when a doctor decides based on CT images alone whether a patient has responded to therapy, it is often based on the size of the lesion,” Khorrami said. “We have found that textural change is a better predictor of whether the therapy is working.

“Sometimes, for example, the nodule may appear larger after therapy because of another reason, say a broken vessel inside the tumor—but the therapy is actually working. Now, we have a way of knowing that.”

Prasanna, a postdoctoral research associate in Madabhushi’s lab, said the study also showed that the results were consistent across scans of patients treated at two different sites and with three different types of immunotherapy agents.

“This is a demonstration of the fundamental value of the program, that our machine-learning model could predict response in patients treated with different immune checkpoint inhibitors,” he said. “We are dealing with a fundamental biological principal.”

Prasanna said the initial study used CT scans from 50 patients to train the computer and create a mathematical algorithm to identify the changes in the lesion. He said the next step will be to test the program on cases obtained from other sites and across different immunotherapy agents. This research recently won an ASCO 2019 Conquer Cancer Foundation Merit Award.

Additionally, Madabhushi said, researchers were able show that the patterns on the CT scans which were most associated with a positive response to treatment and with overall patient survival were also later found to be closely associated with the arrangement of immune cells on the original diagnostic biopsies of those patients.

This suggests that those CT scans actually appear to capturing the immune response elicited by the tumors against the invasion of the cancer—and that the ones with the strongest immune response were showing the most significant textural change and most importantly, would best respond to the immunotherapy, he said.

Madabhushi established the CCIPD at Case Western Reserve in 2012. The lab now includes nearly 60 researchers.

Some of the lab’s most recent work, in collaboration with New York University and Yale University, has used AI to predict which lung cancer patients would benefit from adjuvant chemotherapy based on tissue-slide images. That advancement was named by Prevention Magazine as one of the top 10 medical breakthroughs of 2018.

Other authors on the paper were: Germán Corredor, Mehdi Alilou and Kaustav Bera from biomedical engineering, Case Western Reserve University; Pingfu Fu from population and quantitative health sciences, Case Western Reserve University; Amit Gupta of University Hospitals Cleveland Medical Center; Pradnya Patil of Cleveland Clinic; Priya D. Velu of Weill Cornell Medicine; Rajat Thawani of Maimonides Medical Center; Michael Feldman from Perelman School of Medicine of the University of Pennsylvania; and Vamsidhar Velcheti from NYU-Langone Medical Center.

For more information, contact Mike Scott at mike.scott@case.edu.

Using artificial intelligence to determine whether immunotherapy is working