The findings were published in Science Advances on March 17, 2023.

“For non-small cell lung cancer cases with the LKB1 mutation, standard chemotherapy and immunotherapy treatments are not effective,” says Shaw, senior and co-corresponding author of the study, and director of Salk’s Cancer Center. “Our findings demonstrate there is a way to target these cases using drugs that are FDA-approved or already in clinical trials, so this work could easily be used for a clinical trial in humans.”

Roughly 20 percent of all NSCLCs have the LKB1 genetic mutation, which means there are no effective targeted therapies currently on the market for patients with this cancer type. To create a therapy that could target the LKB1 mutation, the researchers turned to histone deacetylases (HDACs). HDACs are proteins associated with tumor growth and cancer metastasis, with characteristic overexpression in solid tumors. Several HDAC-inhibitor drugs are already FDA-approved (safe for human use) for specific forms of lymphoma, but data on their efficacy in solid tumors or whether tumors bearing specific genetic alterations may exhibit heightened therapeutic potential has been lacking.

Based on previous findings connecting the LKB1 gene to three other HDACs that all rely on HDAC3, the team started by conducting a genetic analysis of HDAC3 in mouse models of NSCLC, discovering an unexpectedly critical role for HDAC3 in multiple models. After establishing that HDAC3 was critical for the growth of the difficult-to-treat LKB1-mutant tumors, the researchers next examined whether pharmacologically blocking HDAC3 could give a similarly potent effect.

The team was curious about testing two drugs, entinostat (an HDAC inhibitor in clinical trials known to target HDAC1 and HDAC3) and FDA-approved trametinib (an inhibitor for a different class of enzymes related to cancer). Tumors often become quickly resistant to trametinib, but co-treatment with a drug that inhibits a protein downstream of HDAC3 helps reduce this resistance. Because that protein relies on HDAC3, the researchers believed that a drug that targets HDAC3 — like entinostat — would help manage trametinib resistance, too.

After treating mice with LKB1-mutated lung cancer with variable treatment regimens for 42 days, the team found that mice given both entinostat and trametinib had 79 percent less tumor volume and 63 percent fewer tumors in their lungs than the untreated mice. Additionally, the team confirmed that entinostat was a viable treatment option in cases where a tumor was resistant to trametinib.

“We thought the whole HDAC enzyme class was directly linked to the cause of LKB1 mutant lung cancer. But we didn’t know the specific role of HDAC3 in lung tumor growth,” says first and co-corresponding author Eichner. “We’ve now shown that HDAC3 is essential in lung cancer, and that it is a druggable vulnerability in therapeutic resistance.”

The findings may lead to clinical trials to test the new regimen in humans, since entinostat is already in clinical trials and trametinib is FDA-approved. Importantly, Shaw sees this discovery as transformative for cancers beyond NSCLC, with potential applications in lymphoma, melanoma, and pancreatic cancer.

“Our lab has committed years to this project, taking small and meaningful steps toward these findings,” says Shaw, holder of the William R. Brody Chair. “This is truly a success story for how basic discovery science can lead to therapeutic solutions in the not-so-distant future.”

“My independent laboratory is fortunate to be part of the Lurie Cancer Center at the Feinberg School of Medicine at Northwestern University, which is very supportive of translational research. We hope that this environment will facilitate the initiation of a clinical trial based on these findings,” says Eichner.

Other authors include Stephanie D. Curtis, Sonja N. Brun, Joshua T. Baumgart, Elijah Trefts, Debbie S. Ross, and Tammy J. Rymoff of Salk; and Caroline K. McGuire and Irena Gushterova of Northwestern University.

The work was supported by the National Institutes of Health (R35CA220538, P01CA120964, K22CA251636, 5T32CA009370, 5F32CA206400, CCSG P30CA014195, and CCSG P30CA23100), Leona M. and Harry B. Helmsley Charitable Trust (#2012-PG-MED002), American Cancer Society (PF-15-037-01-DMC), and Chapman Foundation.

Appearing online March 17 in the journal Science Advances, the finding marks an important first step toward a clinical approach for classifying lesions on the pancreas that are at highest risk of becoming cancerous, potentially enabling their removal before they begin to spread.

If successful, the biomarker-based approach could address the biggest impediment to decreasing the chance of developing pancreatic cancer, which is on the rise and is notorious for silently growing before being discovered, often incidentally, during abdominal scans.

“Even when pancreas cancer is detected at its earliest stage, it almost always has shed cells throughout the body, and the cancer returns,” said senior author Peter Allen, M.D., chief of the Division of Surgical Oncology at in the Department of Surgery at Duke University School of Medicine.

“That’s why we shifted our focus to these precancerous cysts, known as intraductal papillary mucinous neoplasms, or IPMNs,” Allen said. “Most IPMNs will never progress to pancreas cancer, but by distinguishing which ones will progress, we are creating an opportunity to prevent an incurable disease from developing.”

Allen and colleagues used a sophisticated molecular biology tool called digital spatial RNA profiling to home in on specific areas of the cyst with high- and low-grade areas of abnormal cell growth.

Previous methods to characterize IPMNs have been less precise and have not been able to identify particularly accurate markers of cancer risk. Digital spatial profiling, however, allows researchers to choose individual groups of cells for analysis. This enabled the Duke researchers to identify a host of genetic mutations that both fuel and potentially suppress pancreatic cancer development.

The team also identified markers for discriminating between the two leading variants of IPMN and found distinct markers for defining a third common variant that generally results in less aggressive disease.

“We found very distinct markers for high-grade cell abnormalities, as well as for slow-growing subtypes,” Allen said. “Our work now is focusing on finding it in the cyst fluid. If we can identify these unique markers in cyst fluid, it could provide the basis for a protein biopsy that would guide whether we should remove the cyst before cancer develops and spreads.”

Allen said current diagnostic strategies — including clinical, radiographic, laboratory, endoscopic, and cytologic analysis — have an overall accuracy of approximately 60%.

“Pancreatic cancer is on the rise and, if the current trajectory continues, it will become the second-leading cause of cancer death in the United States in the next few years,” Allen said, noting it’s unknown what is driving the cancer’s increased prevalence.

He said some studies suggest inflammation plays a role. A clinical trial at Duke, led by Allen, is testing whether an anti-inflammatory therapy could reduce the development of cancer in patients with IPMN.

In addition to Allen, study authors include Matthew K. Iyer, Chanjuan Shi, Austin M. Eckhoff, Ashley Fletcher, and Daniel P. Nussbaum.

The study received funding support from the National Cancer Institute (RO1 CA182076).

Using the National Cancer Institute’s (NCI) common myths and misconceptions about cancer, Johnson and his team found that 97% of the answers were correct. However, this finding comes with some important caveats, including a concern amongst the team that some of the ChatGPT answers could be interpreted incorrectly. “This could lead to some bad decisions by cancer patients. The team suggested caution when advising patients about whether they should use chatbots for information about cancer,” says Johnson.

The study found reviewers were blinded, meaning they didn’t know whether the answers came from the chatbot or the NCI. Though the answers were accurate, reviewers found ChatGPT’s language was indirect, vague, and in some cases, unclear.

“I recognize and understand how difficult it can feel for cancer patients and caregivers to access accurate information,” says Johnson. “These sources need to be studied so that we can help cancer patients navigate the murky waters that exist in the online information environment as they try to seek answers about their diagnoses.”

Incorrect information can harm cancer patients. In a previous study by Johnson and his team published in the Journal of the National Cancer Institute, they found that misinformation was common on social media and had the potential to harm cancer patients.

The next steps are to evaluate how often patients are using chatbots to seek out information about cancer, what questions they are asking, and whether AI chatbots provide accurate answers to uncommon or unusual questions about cancer.

The study was supported by the National Institutes of Health/National Cancer Institute including P30 CA042014 and Huntsman Cancer Foundation.

The findings, published by University of Arizona researchers in the Journal of Geophysical Research, underscore the fragility of a very large glacial system that could lead to the loss of a significant volume of ice and National Park Service land and would contribute a measurable volume to global sea level rise.

“The loss of this glacier would likely be the largest loss of ice from an Alaskan glacier within this century,” said lead study author Brandon Tober, a doctoral student in the UArizona Department of Geosciences.

The area in front of Malaspina Glacier, a permafrost zone with pure ice beneath the surface, is “wasting away” in the face of rising global temperatures, Tober said. Permafrost refers to ground that remains frozen for two or more years.

“As this coastal barrier erodes and gives way to large lagoons, primarily through the collapse of ice cliffs, ocean water may eventually gain access to the glacier,” Tober said. “Once it gets to the front of the glacier, it may melt the ice even faster and initiate the glacier’s retreat.”

Forming an expansive ice sheet located right on the shore of southeast Alaska, Malaspina is the world’s largest piedmont glacier, a type of glacier that flows from steep mountains onto a broad plain, essentially forming a “pancake of ice” that spills out onto a broad coastal plain from the St. Elias Mountains. A thin land barrier separates the glacier from the relatively warm waters of the Gulf of Alaska. Historical satellite imagery shows these water bodies expanding over time, forming a lagoon system directly in front of the glacier over the past few decades.

Traditionally, researchers rely on mathematical models to gauge the thickness of glaciers, Tober said, but they vary widely in their ability to accurately predict the thickness of glaciers. These models often rely on measurements of how fast the glacier moves across the surface to make predictions about the glacier’s depth, similar to the way a river’s water flow rates are used to gain insights about its depth and the shape of its bed.

“We know that glaciers in Alaska are melting and thinning rapidly in many places, but we don’t accurately know how thick they are, and therefore we can’t accurately predict future mass loss,” Tober said. “If we don’t know the thickness and bed topography, we can’t accurately model their future evolution.”

To gain a better idea of Malaspina’s future, the researchers needed to get a detailed “body scan” of its shape and thickness. To do this, Tober’s research group used the Arizona Radio Echo Sounder, or ARES, an instrument designed and built by a team led by Jack Holt, a professor at the UArizona Lunar and Planetary Laboratory and Department of Geosciences, and one of the paper’s co-authors. Holt’s research group specializes in using geophysical research methods, primarily radar, to study features on Earth and Mars.

ARES was mounted in an airplane as part of Operation IceBridge, a NASA-funded mission tasked with measuring annual changes in the thickness of glaciers, sea ice and ice sheets in Greenland, Alaska and Antarctica from airplanes between 2009 and 2021.

While the plane crisscrossed the vast, icy expanse, its ice-penetrating radar “X-rayed” the glacier, resulting in a full “3D body scan” of the glacier and underlying bedrock. The measurements revealed that Malaspina glacier sits largely below sea level and is cut by several channels at its bed that extend at least 21 miles from where the glacier meets the shore up toward its source in the Saint Elias Mountains.

The combination of the glacier’s location with respect to the sea level and the continued loss of its coastal barrier may provide pathways for ocean waters to access large areas of the glacier’s bed along these channels, the researchers write in their paper. Assuming this leads to large-scale shedding of ice masses and the glacier’s retreat, the researchers conclude that Malaspina has the potential to contribute 560 cubic kilometers, or 134 cubic miles, of ice to the ocean. In other words, Malaspina alone could raise global sea level by 1.4 millimeters, or just under 1/16 of an inch.

“This might not sound like much, but to put this in perspective, all Alaskan glaciers combined contribute about 0.2 millimeters per year to global sea level rise — a rate that tops all other glaciated regions on Earth apart from the Greenland and Antarctic ice sheets,” Tober said.

The study makes Malaspina the most extensively radar-mapped glacier in Alaska, according to Tober’s team. While glaciers in other parts of the world have been mapped to similar levels of detail, their Alaskan counterparts have eluded accurate measurements because they consist of what is known as temperate or “warm” ice.

“The glacier’s crevasses often have water in them, and that makes it difficult to get radar energy down to the bed of the glacier and back up to the instrument,” Tober said.

Overcoming that challenge was part of the motivation to build ARES.

The radar scans revealed that glaciological models overestimate Malaspina’s volume by more than 30%. Still, the glacier, which was measured to be just over half a mile thick at its center, boasts 10 times the total volume of all the glaciers in the Swiss Alps.

“We can speculate that the channels, the big troughs beneath the glacier, are routing meltwater that comes out at the coast,” Tober said.

The observed expanse of lagoons across Malaspina’s foreland over the past few decades is largely what alerted a team of researchers including Holt to the fact that the coastal barrier in front of Malaspina Glacier is wasting away, raising questions about the glacier’s stability. The team, which consists of researchers from the UArizona, the University of Alaska Fairbanks, the University of Montana and the National Park Service, was awarded a grant by the National Science Foundation to further investigate the potential demise of the world’s largest piedmont glacier.

Sydney Mooneyham, a co-author on this paper who graduated from the UArizona School of Geography, Development and Environment, mapped the expanse of the lagoons across Malaspina’s foreland over the course of about 50 years’ worth of images taken by Landsat, a series of Earth-observing satellites launched to study and monitor Earth’s landmasses.

Another motivation to focus on Malaspina Glacier, Tober said, came from the fact that it is located in the largest national park in the U.S., the Wrangell Saint Elias National Park and Preserve. At 13.2 million acres, it is larger than Yellowstone National Park, Yosemite National Park and the country of Switzerland combined, according to the National Park Service.

“The potential loss of Malaspina and opening of a new bay along Alaska’s coastline may be the largest landscape transformation within the U.S. that we could witness during this century,” Tober said, “and it may lead to the loss of up to 500 square miles of park land.”

“With the help of a quantum annealer, we demonstrated a new way to pattern magnetic states,” said Alejandro Lopez-Bezanilla, a virtual experimentalist in the Theoretical Division at Los Alamos National Laboratory. Lopez-Bezanilla is the corresponding author of a paper about the research in Science Advances.

“We showed that a magnetic quasicrystal lattice can host states that go beyond the zero and one bit states of classical information technology,” Lopez-Bezanilla said. “By applying a magnetic field to a finite set of spins, we can morph the magnetic landscape of a quasicrystal object.”

“A quasicrystal is a structure composed by the repetition of some basic shapes following rules different to those of regular crystals,” he said.

For this work with Cristiano Nisoli, a theoretical physicist also at Los Alamos, a D-Wave quantum annealing computer served as the platform to conduct actual physical experiments on quasicrystals, rather than modeling them. This approach “lets matter talk to you,” Lopez-Bezanilla said, “because instead of running computer codes, we go straight to the quantum platform and set all the physical interactions at will.”

The ups and downs of qubits

Lopez-Bezanilla selected 201 qubits on the D-Wave computer and coupled them to each other to reproduce the shape of a Penrose quasicrystal.

Since Roger Penrose in the 1970s conceived the aperiodic structures named after him, no one had put a spin on each of their nodes to observe their behavior under the action of a magnetic field.

“I connected the qubits so all together they reproduced the geometry of one of his quasicrystals, the so-called P3,” Lopez-Bezanilla said. “To my surprise, I observed that applying specific external magnetic fields on the structure made some qubits exhibit both up and down orientations with the same probability, which leads the P3 quasicrystal to adopt a rich variety of magnetic shapes.”

Manipulating the interaction strength between qubits and the qubits with the external field causes the quasicrystals to settle into different magnetic arrangements, offering the prospect of encoding more than one bit of information in a single object.

Some of these configurations exhibit no precise ordering of the qubits’ orientation.

“This can play in our favor,” Lopez-Bezanilla said, “because they could potentially host a quantum quasiparticle of interest for information science.” A spin quasiparticle is able to carry information immune to external noise.

A quasiparticle is a convenient way to describe the collective behavior of a group of basic elements. Properties such as mass and charge can be ascribed to several spins moving as if they were one.

Though their rugged location once protected mountain forests from deforestation, they have been increasingly exploited since the turn of the 21^st century as lowland areas become depleted or subject to protection. A team of scientists led by Xinyue He (@xinyue_he), Dominick Spracklen and Joseph Holden at Leeds University in the United Kingdom, and Zhenzhong Zeng at the Southern University of Science and Technology in China wanted to investigate the extent and global distribution of mountain forest loss.

To do this, the team tracked changes in mountain forests on a yearly basis from 2001 to 2018. They quantified both losses and gains in tree cover, estimated the rate at which change is occurring, compared different elevations and types of mountain forests — boreal, temperate, tropical — and explored the impacts of this forest loss on biodiversity.

“Knowledge of the dynamics of forest loss along elevation gradients worldwide is crucial for understanding how and where the amount of forested area available for forest species will change as they shift in response to warming,” the authors write.

Logging was the biggest driver of mountain forest loss overall (42%), followed by wildfires (29%), shifting or “slash-and-burn” cultivation (15%), and permanent or semi-permanent agriculture (10%), though the importance of these different factors varied from region to region. Significant loss occurred in Asia, South America, Africa, Europe, and Australia, but not in North America and Oceania.

Worryingly, the rate of mountain forest loss seems to be accelerating: the annual rate of loss increased by 50% from 2001-2009 to 2010-2018, when we lost approximately 5.2 million hectares of mountain forests per year. The authors write that this acceleration is probably largely due to rapid agricultural expansion into highland areas in mainland Southeast Asia, as well as increased logging of mountain forests due to either depletion of lowland forests or because these lowland forests became protected.

Tropical mountain forests experienced the most loss — 42% of the global total — and the fastest acceleration rate, but also had a faster rate of regrowth compared to mountain forests in temperate and boreal regions. Overall, the researchers observed some signs of tree cover regrowth in 23% of the areas that lost forest.

Protected areas experienced less forest loss than unprotected areas, but the researchers caution that this might not be enough to preserve threatened species. “Regarding sensitive species in biodiversity hotspots, the critical issue extends beyond simply preventing forest loss,” the authors write. “We must also maintain the integrity of forests in large enough zones to allow natural movements and sufficient space for ranging species.”

The authors also emphasize the importance of considering human livelihoods and wellbeing when developing forest protection strategies and interventions. “Any new measures to protect mountain forests should be adapted to local conditions and contexts and need to reconcile the need for enhanced forest protection with ensuring food production and human wellbeing.”

This research was supported by the Southern University of Science and Technology, the University of Leeds, and the National Natural Science Foundation of China.

The invasive species has been calculated to cost more than £165 million to manage every year in the UK alone. Its presence can blight property purchases for households across the country.

This has led to the development of different ways of trying to control it but with sustainability becoming increasingly important, understanding the effect of these management methods is vital.

A new study, led by biosciences lecturer Dr Sophie Hocking and looking at the entire life cycle and long term impacts of different management approaches, has just been published in online journal Scientific Reports.

Dr Hocking said: “In light of the current climate emergency and biodiversity crisis, invasive species management and sustainability have never been so important.

“Both of these are intrinsically linked — we know that invasive species can cause substantial negative ecological, social and economic impacts, and the way we manage these species should mitigate against this in a sustainable way to ensure we are not doing more harm than good.

“Although there has been more research into how we can best manage the plant, little is known about how sustainable these approaches are.”

This study follows on from previous research which has put Swansea University at the forefront of Japanese knotweed expertise and understanding.

Back in 2012 Professor Dan Eastwood and Dr Dan Jones launched the world’s largest knotweed control field trial which tested the main physical, chemical and integrated methods of controlling the species. The research has been undertaken in close partnership with Complete Weed Control’s Managing Director Ian Graham and Advanced Invasives, a spinout company, headed by Dr Jones.

This field study provided valuable information for Dr Hocking’s work. Using a life cycle assessment (LCA) — a methodology for assessing environmental impacts associated with all the stages of the life cycle of a commercial process — to find out the relative environmental impacts of a range of chemical and physiochemical knotweed management methods.

The researchers went beyond a focus on the use and end-of life if these methods and assessed the environmental impacts of different management methods including the production of materials and herbicides required to achieve knotweed control; something that is often overlooked when we evaluate sustainability. For the study, the team selected methods commonly used for knotweed management and used real-world data on time consumption, amount of materials used and economic costs to evaluate their relative environmental impacts.

Of the methods tested, they found that the simplest approach — glyphosate-based foliar spray control methods — used the least materials, had the lowest environmental impacts, the lowest economic costs and is, therefore, the most sustainable approach to tackle knotweed management. The findings are of significance to those working with or are affected by the presence of Japanese knotweed on their land

Dr Hocking added: “Currently there is a big conversation around the sustainability of herbicides and the ecological and human-health impacts of this. Social perceptions of the ways we manage invasive plants are really important, but we need our understanding of sustainability to be rooted in empirical evidence.

“We hope that this research will contribute to our wider understanding of the sustainability of different approaches in invasive plant management and help to inform current knotweed management practice.”