Controlling prostheses with the power of thought

 A neuroprosthesis. Artificial hands, arms, or legs can restore mobility to people with disabilities. The study investigated how the brain learns to control such prostheses via brain-computer interfaces.
Image Credit: © Sebastian Lehmann

Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have discovered that the brain reorganizes itself extensively across several brain regions when it learns to perform movements in a virtual environment with the help of a brain-computer interface. The scientists were thus able to show how the brain adapts when controlling motor prostheses. The findings not only help to advance the development of brain-computer interfaces, but also improve our understanding of the fundamental neural processes underlying motor learning.

In order to perform precise movements, our brain's motor system must continuously recalibrate itself. If we want to shoot a basketball, this works well with a familiar basketball, but requires extra practice with a lighter or heavier ball. Our brain uses the deviations from the expected (throw) result as an error signal to learn better commands for the next throw. The brain must also perform this task when it wants to control a movement via a brain-computer interface (BCI), for example, that of a neuroprosthesis. Until now, it was unclear which regions of the brain reflect the expected result of the movement (the trajectory of the ball), which reflect the error signal, and which reflect the corrected movement command that aims to compensate for the previous error.

In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

MIT experiments have revealed the existence of “microcompartments,” shown in yellow, within the 3D structure of the genome. These compartments are formed by tiny loops that may play a role in gene regulation.
Illustration Credit: Ed Banigan, edited by MIT News
(CC BY-NC-ND 4.0)

Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”

Researchers use nanotubes to improve blood flow in bioengineered tissues

Assistant Professors Ying Wang (Department of Biomedical Engineering) and Yingge Zhou (School of Systems Science and Industrial Engineering) collaborated on research about engineered tissues.
Photo Credit: Jonathan Cohen.

When biomedical researchers need to test their latest ideas, they often turn to engineered human tissue that mimics the responses in our own bodies. It’s become an important intermediary step before human clinical trials.

One limiting factor: The cells need blood circulation to survive, and achieving that can be difficult in three-dimensional cell structures. Without proper vascular systems — even primitive ones — engineered tissue faces restricted size and functionality, even developing necrotic regions of dead cells.

New research from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science offers a possible solution to the problem. In a paper recently published in the journal Biomedical Materials, Assistant Professors Ying Wang and Yingge Zhou show how the latest nanomanufacturing techniques can create a better artificial vascular system.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Lung-on-a-Chip Defends Itself

Ankur Singh and Rachel Ringquist point to the microscopic lung-on-a-chip that has a built-in immune system.
Photo Credit: Courtesy of Georgia Institute of Technology

On a clear polymer chip, soft and pliable like a gummy bear, a microscopic lung comes alive — expanding, circulating, and, for the first time, protecting itself like a living organ. 

For Ankur Singh, director of Georgia Tech’s Center for Immunoengineering, watching immune cells rush through the chip took his breath away. Singh co-directed the study with longtime collaborator Krishnendu “Krish” Roy, former Regents Professor and director of the NSF Center for Cell Manufacturing Technologies at Tech and now the Bruce and Bridgitt Evans dean of engineering and University Distinguished Professor at Vanderbilt University. Rachel Ringquist, Roy’s graduate student, and now a postdoctoral fellow with Singh, led the work as part of her doctoral dissertation. 

“That was the ‘wow’ moment,” Singh said. “It was the first time we felt we had something close to a real human lung.”

Lung-on-a-chip platforms provide researchers a window into organ behavior. They are about the size of a postage stamp, etched with tiny channels and lined with living human cells. Roy and Singh’s innovation was adding a working immune system — the missing piece that turns a chip into a true model of how the lung fights disease.

Now, researchers can watch how lungs respond to threats, how inflammation spreads, and how healing begins.

Visualisation of blood flow sharpens artificial heart

To be able to observe the blood flow in the artificial heart in real time, the researchers had to build a full-scale model of the human circulatory system.
Photo Credit:Emma Busk Winquist

Using magnetic cameras, researchers at Linköping University have examined blood flow in an artificial heart in real time. The results make it possible to design the heart in a way to reduce the risk of blood clots and red blood cells breakdown, a common problem in today’s artificial hearts. The study, published in Scientific Reports, was done in collaboration with the company Scandinavian Real Heart AB, which is developing an artificial heart.

“The heart is a muscle that never rests. It can never rest. The heart can beat for a hundred years without being serviced or stopping even once. But constructing a pump that can function in the same way – that’s a challenge,” says Tino Ebbers, professor of physiology at Linköping University.

Nearly 9,000 heart transplants are performed worldwide per year, and the number keeps increasing. So does the number of people queuing for a new heart, with some 2,800 on the waiting list in the EU alone, and around 3,400 in the US.

Most of the patients whose heart does not work at all are currently connected to a machine that takes care of their blood circulation for them. It is a large device, and the patient is confined to their hospital bed. For those patients, an artificial heart could be an option while waiting for a donor heart.

New Diagnostic Tool Developed at Dana-Farber Revolutionizes Acute Leukemia Diagnosis

Volker Hovestadt, PhD
Assistant Professor, Pediatrics, Harvard Medical School Independent Investigator/Assistant Professor, Department of Pediatric Oncology, Dana-Farber Cancer Institute
Photo Credit: Courtesy of Dana-Farber Cancer Institute

Researchers at Dana-Farber Cancer Institute have developed a groundbreaking diagnostic tool that could transform the way acute leukemia is identified and treated. The tool, called MARLIN (Methylation- and AI-guided Rapid Leukemia Subtype Inference), uses DNA methylation patterns and machine learning to classify acute leukemia with speed and accuracy. This tool has the potential to significantly improve patient care by allowing faster and more precise treatment decisions.

Acute leukemia is an aggressive blood cancer that requires accurate diagnosis to guide treatment. Current diagnostic methods, which rely on a combination of molecular and cytogenetic tests, often take days or even weeks to complete. MARLIN, however, can provide results in as little as two hours from the time of biopsy. By providing rapid and detailed insights into leukemia subtypes, MARLIN could enable clinicians to make treatment decisions sooner and with more complete information.

Possible breakthrough in the development of effective biomaterials

Professor Dr. Shikha Dhiman from the Department of Chemistry of JGU
Photo Credit: © Ankit Sakhuja

When model cell membranes bind to biomaterials, it is not the binding strength but the speed of the receptors in the membranes that is crucial

Many hopes rested on so-called tissue engineering: With the help of stem cells, skin and other organs could be grown, thereby enabling better wound healing and better transplants. Although some of this is already a reality, the level expected around 20 years ago has not yet been achieved because the stem cells do not always bind to the required host material as they should in theory. An international research team led by chemist Professor Shikha Dhiman from Johannes Gutenberg University Mainz (JGU) has now found the reason for this: "Whether an interaction between model cell membrane and matrix material occurs depends not only on the strength of the interaction but also on the speed at which the binding partner molecules move. The understanding of this interaction that we have now gained is crucial for the development of effective biomaterials," says Dhiman. The team's results were recently published in the renowned scientific journal PNAS.

Shining a light on germs

Microbe hunters: Empa researchers Paula Bürgisser and Giacomo Reina from the Nanomaterials in Health laboratory in St. Gallen.
Photo Credit: Empa

Light on – bacteria dead. Disinfecting surfaces could be as simple as that. To turn this idea into a weapon against antibiotic-resistant germs, Empa researchers are developing a coating whose germicidal effect can be activated by infrared light. The plastic coating is also skin-friendly and environmentally friendly. A first application is currently being implemented for dentistry.

Antibiotic-resistant bacteria and emerging viruses are a rapidly increasing threat to the global healthcare system. Around 5 million deaths each year are linked to antibiotic-resistant germs, and more than 20 million people died during the COVID-19 virus pandemic. Empa researchers are therefore working on new, urgently needed strategies to combat such pathogens. One of the goals is to prevent the spread of resistant pathogens and novel viruses with smart materials and technologies.

Surfaces that come into constant contact with infectious agents, such as door handles in hospitals or equipment and infrastructure in operating theaters, are a particularly suitable area of application for such materials. An interdisciplinary team from three Empa laboratories, together with the Czech Palacký University in Olomouc, has now developed an environmentally friendly and biocompatible metal-free surface coating that reliably kills germs. The highlight: The effect can be reactivated again and again by exposing it to light.

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice.
Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University

Collagen, the body’s most abundant protein, has long been viewed as a predictable structural component of tissues. However, a new study led by Rice University’s Jeffrey Hartgerink and Tracy Yu, in collaboration with Mark Kreutzberger and Edward Egelman at the University of Virginia (UVA), challenges that notion, revealing an unexpected confirmation in collagen structure that could reshape biomedical research.

The researchers used advanced cryo-electron microscopy (cryo-EM) to determine the atomic structure of a packed collagen assembly that deviates from the traditionally accepted right-handed superhelical twist. Published in ACS Central Science, the study suggests collagen’s structural diversity may be greater than previously believed.

“This work fundamentally changes how we think about collagen,” said Hartgerink, professor of chemistry and bioengineering. “For decades, we have assumed that collagen triple helices always follow a strict structural paradigm. Our findings show that collagen assemblies can adopt a wider range of conformations than previously thought.”

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

First atlas of the human ovary with cell-level resolution is a step toward artificial ovary

University of Michigan BME graduate student Jordan Machlin shows to prof. Ariella Shikanov and fellows grad student Margaret Brunette the images of oocytes in ovarian tissue she collected using RNA-fluorescence in situ hybridization.
Photo Credit: Marcin Szczepanski/Lead Multimedia Storyteller, Michigan Engineering

A new “atlas” of the human ovary provides insights that could lead to treatments restoring ovarian hormone production and the ability to have biologically related children, according to University of Michigan engineers.

This deeper understanding of the ovary means researchers could potentially create artificial ovaries in the lab using tissues that were stored and frozen before exposure to toxic medical treatments such as chemotherapy and radiation. Currently, surgeons can implant previously frozen ovarian tissue to temporarily restore hormone and egg production. However, this does not work for long because so few follicles—the structures that produce hormones and carry eggs—survive through reimplantation, the researchers say.

The new atlas reveals the factors that enable a follicle to mature, as most follicles wither away without releasing hormones or an egg. Using new tools that can identify what genes are being expressed at a single-cell level within a tissue, the team was able to home in on ovarian follicles that carry the immature precursors of eggs, known as oocytes.

Rapid, simultaneous detection of multiple bacteria achieved with handheld sensor

Marking bacteria electrochemically for rapid detection   
From left: Image of bacteria labeled with electrochemical markers, an electrochemical instrument to measure the data, and an image of the data displayed on a smartphone.     
Image Credit: Hiroshi Shiigi, Osaka Metropolitan University

Hearing the words E. coli or salmonella and food poisoning comes to mind. Rapid detection of such bacteria is crucial in preventing outbreaks of foodborne illness. While the usual practice is to take food samples to a laboratory to see the type and quantity of bacteria that forms in a petri dish over a span of days, an Osaka Metropolitan University research team has created a handheld device for quick on-site detection.

Led by Professor Hiroshi Shiigi of the Graduate School of Engineering, the team experimented with a biosensor that can simultaneously detect multiple disease-causing bacterial species within an hour.

“The palm-sized device for detection can be linked to a smartphone app to easily check bacterial contamination levels,” Professor Shiigi explained.

His team synthesized organic metallic nanohybrids of gold and copper that do not interfere with each other, so that electrochemical signals can be distinguished on the same screen-printed electrode chip of the biosensor. These organic−inorganic hybrids are made up of conductive polymers and metal nanoparticles. The antibody for the specific target bacteria was then introduced into these nanohybrids to serve as electrochemical labels.

Airy cellulose from a 3D printer

Complexity and lightness: Empa researchers have developed a 3D printing process for biodegradable cellulose aerogel.
Photo Credit: Empa

Ultra-light, thermally insulating and biodegradable: Cellulose-based aerogels are versatile. Empa researchers have succeeded in 3D printing the natural material into complex shapes that could one day serve as precision insulation in microelectronics or as personalized medical implants.

At first glance, biodegradable materials, inks for 3D printing and aerogels don't seem to have much in common. All three have great potential for the future, however: "green" materials do not pollute the environment, 3D printing can produce complex structures without waste, and ultra-light aerogels are excellent heat insulators. Empa researchers have now succeeded in combining all these advantages in a single material. And their cellulose-based, 3D-printable aerogel can do even more.

The miracle material was created under the leadership of Deeptanshu Sivaraman, Wim Malfait and Shanyu Zhao from Empa's Building Energy Materials and Components laboratory, in collaboration with the Cellulose & Wood Materials and Advanced Analytical Technologies laboratories as well as the Center for X-ray Analytics. Together with other researchers, Zhao and Malfait had already developed a process for printing silica aerogels in 2020. No trivial task: Silica aerogels are foam-like materials, highly open porous and brittle. Before the Empa development, shaping them into complex forms had been pretty much impossible. "It was the logical next step to apply our printing technology to mechanically more robust bio-based aerogels," says Zhao.

The researchers chose the most common biopolymer on Earth as their starting material: cellulose. Various nanoparticles can be obtained from this plant-based material using simple processing steps. Doctoral student Deeptanshu Sivaraman used two types of such nanoparticles – cellulose nanocrystals and cellulose nanofibers – to produce the "ink" for printing the bio-aerogel.

The Rotisserie-Inspired Device That Could Revolutionize Cancer Surgery

The Zavaleta Lab’S Raman Rotisserie Device Creates a Map of the Surface of a Resected Tumor to Aid Surgeons in the Operating Room.
Photo Credit: Alex Czaja

Like many Texans, Cristina Zavaleta grew up enjoying the culinary delights of the state’s famous smokehouse BBQs. She couldn’t have imagined that those humble rotisseries of her childhood would one day inspire a game-changing device for the operating room that could help surgeons prevent tumor recurrence.

On a team excursion to Disneyland, the WiSE Gabilan Assistant Professor of Biomedical Engineering and her students were reminded of rotisseries when they encountered a food vendor at the Star Wars-themed land, Galaxy’s Edge. It was a lightbulb moment. The rotisserie configuration was a perfect way of intricately scanning excised tumors, with the help of the Zaveleta Lab’s unique nanoparticles, to light up where the cancerous tissue may not have been entirely removed from the patient. Surgeons could then be guided to precisely remove the remaining tumor, all while the patient is still under anesthesia. The result would reduce the need for traumatic repeat surgeries and potential cancer recurrence and metastasis.

Zavaleta and her team built the device, which they dubbed the Raman Rotisserie. It physically rotates a tumor specimen and works in conjunction with an imaging technique known as Raman spectroscopy, which scans the surface of the excised tumor. Their research, which aims to improve the success rate of breast cancer lumpectomies, has now been published in NPJ Imaging.

Discovery could end global amphibian pandemic

Panamanian golden frog
Photo Credit: Brian Gratwicke/U.S. Fish & Wildlife Service

A fungus devastating frogs and toads on nearly every continent may have an Achilles heel. Scientists have discovered a virus that infects the fungus, and that could be engineered to save the amphibians.

The fungus, Batrachochytrium dendrobatidis or Bd, ravages the skin of frogs and toads, and eventually causes heart failure. To date it has contributed to the decline of over 500 amphibian species, and 90 possible extinctions including yellow-legged mountain frogs in the Sierras and the Panamanian golden frog. 

A new paper in the journal Current Biology documents the discovery of a virus that infects Bd, and which could be engineered to control the fungal disease.

The UC Riverside researchers who found the virus are excited about the implications of their discovery. In addition to helping them learn about how fungal pathogens rise and spread, it offers the hope of ending what they call a global amphibian pandemic. 

“Frogs control bad insects, crop pests, and mosquitoes. If their populations all over the world collapse, it could be devastating,” said UCR microbiology doctoral student and paper author Mark Yacoub. 

“They’re also the canary in the coal mine of climate change. As temperatures get warmer, UV light gets stronger, and water quality gets worse, frogs respond to that. If they get wiped out, we lose an important environmental signal,” Yacoub said. 

Pollen is a promising sustainable tool in the bone regeneration process

Scientists have used pollen to grow hydroxyapatite capsules, so the mineral can better support bone regeneration
Photo Credit: Alex Jones

A study has shown pollen grains can be used as green templates for producing biomaterials, showcasing their potential to support drug delivery and bone regeneration.

With an increasingly ageing population, bone fractures are becoming more common. Bone is generally able to self-repair but if the fracture is too big or the person affected too fragile, as for example people with osteoporosis, the use of bone fillers can help.

Hydroxyapatite (HAp) is an inorganic mineral present in human bone and teeth, which can be used to support bone regeneration. It makes up somewhere between 65 per cent and 70 per cent of the weight of human bone. Healthcare professionals often use synthetic and natural HAp when carrying out bone repair treatments.

A team at the University of Portsmouth has worked with international colleagues to explore sustainable ways to improve the process. 

They examined the feasibility of using pollen grains as bio-templates for growing calcium phosphate minerals in the lab - particularly hydroxyapatite (HAp) and β-tricalcium phosphate (TCP), which are types of calcium phosphate used for bone repair.

Scientists identify Achilles heel of lung cancer protein

Researchers have shown for the first time that a crucial interface in a protein that drives cancer growth could act as a target for more effective treatments.

The study, led by the Science and Technology Facilities Council (STFC) Central Laser Facility (CLF) with support from the Imaging Therapies and Cancer Group at King's, used advanced laser imaging techniques to identify structural details of a mutated protein which help it to evade drugs that target it.

The study was published in the journal Nature Communications and lays the groundwork for future research into more effective, long-lasting cancer therapies.

The Epidermal Growth Factor Receptor (EGFR) is a protein that sits on the surface of cells and receives molecular signals that tell the cell to grow and divide. In certain types of cancer, mutated EGFR stimulate uncontrolled growth, resulting in tumors.

Various cancer treatments block and inhibit mutant EGFR to prevent tumor formation, but these are limited as eventually cancerous cells commonly develop further EGFR mutations that are resistant to treatment.

Until now, how exactly these drug-resistant EGFR mutations drive tumor growth was not understood, hindering our ability to develop treatments that target them.

Purdue researchers create biocompatible nanoparticles to enhance systemic delivery of cancer immunotherapy

Purdue University researchers are developing and validating patent-pending nanoparticles (left) to enhance immunotherapy effects against tumors. The nanoparticles are modified with adenosine triphosphate, or ATP, to recruit dendritic cells (right), which are immune cells that recognize tumor antigens and bring specialized immune cells to fight off tumors.
Image Credit: Yoon Yeo

Purdue University researchers are developing and validating patent-pending poly (lactic-co-glycolic acid), or PLGA, nanoparticles modified with adenosine triphosphate, or ATP, to enhance immunotherapy effects against malignant tumors.

The nanoparticles slowly release drugs that induce immunogenic cell death, or ICD, in tumors. ICD generates tumor antigens and other molecules to bring immune cells to a tumor’s microenvironment. The researchers have attached ATP to the nanoparticles, which also recruits immune cells to the tumor to initiate anti-tumor immune responses. 

Yoon Yeo leads a team of researchers from the College of Pharmacy, the Metabolite Profiling Facility in the Bindley Bioscience Center, and the Purdue Institute for Cancer Research to develop the nanoparticles. Yeo is the associate department head and Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics and Biomedical Engineering; she is also a member of the Purdue Institute for Drug Discovery and the Purdue Institute for Cancer Research.

The researchers validated their work using paclitaxel, a chemotherapy drug used to treat several types of cancers. They found that tumors grew slower in mice treated with paclitaxel enclosed within ATP-modified nanoparticles than in mice treated with paclitaxel in non-modified nanoparticles.

“When combined with an existing immunotherapy drug, the ATP-modified, paclitaxel-loaded nanoparticles eliminated tumors in mice and protected them from rechallenge with tumor cells,” Yeo said.