Tag: Academic research

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The Download: NASA’s nuclear spacecraft and unveiling our AI 10

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

NASA is building the first nuclear reactor-powered interplanetary spacecraft. How will it work? 

Just before Artemis II began its historic slingshot around the moon, NASA revealed an even grander space travel plan. By the end of 2028, the agency aims to fly a nuclear reactor-powered interplanetary spacecraft to Mars. 

A successful mission would herald a new era in spaceflight—and might just give the US the edge in the race against China. But the project remains shrouded in mystery. 

MIT Technology Review picked the brains of nuclear power and propulsion experts to find out how the nuclear-powered spacecraft might work. Here’s what we discovered. 

—Robin George Andrews 

This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here. 

Coming soon: our 10 Things That Matter in AI Right Now 

Each year, we compile our 10 Breakthrough Technologies list, featuring our educated predictions for which technologies will change the world. Our 2026 list, however, was harder to wrangle than normal. Why? We had so many worthy AI candidates we couldn’t fit them all in!  

That got us thinking: what if we made an entirely new list all about AI? Before we knew it, we had the beginnings of what we’re calling 10 Things That Matter in AI Right Now.  

On April 21, we’ll unveil the list on stage at our signature AI conference, EmTech AI, and then publish it online later that day. If you want to be among the first to see it, join us at EmTech AI or become a subscriber to livestream the announcement.  

Find out more about the list’s methodology and aims here. 

—Niall Firth & Amy Nordrum 

MIT Technology Review Narrated: this company is developing gene therapies for muscle growth, erectile dysfunction, and “radical longevity” 

In January, a handful of volunteers were injected with two experimental gene therapies as part of an unusual clinical trial. Its long-term goal? To achieve radical human life extension.  

The therapies are designed to support muscle growth. The company behind them, Unlimited Bio, also plans to trial similar therapies in the scalp (for baldness) and penis (for erectile dysfunction). But some experts are concerned about the plans.  

Find out why the trial has divided opinion. 

—Jessica Hamzelou 

This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we publish each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released. 

The must-reads 

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology. 

1 Google, Microsoft, and Meta track users even when they opt out 
According to an independent audit, they may be racking up billions in fines. (404 Media)  
+ How our digital devices put our privacy at risk. (Ars Technica) 
+ Privacy’s next frontier is AI “memories.” (MIT Technology Review) 
 
2 OpenAI has a new cybersecurity model—and strategy 
GPT-5.4-Cyber is designed specifically for defensive cybersecurity work. (Reuters $) 
+ OpenAI has joined Anthropic in focusing on cybersecurity recently. (Wired $) 
+ Like Anthopic, its latest model is only available to verified testers. (NYT $) 
+ AI is already making online crimes easier. It could get much worse. (MIT Technology Review) 

3 Amazon is buying satellite firm Globalstar in a bid to rival Starlink   
The $11.6 billion deal targets the lucrative satellite internet market. (WSJ $)  
+ Apple has chosen Amazon satellites for iPhone. (Ars Technica) 
 
4 What it’s like to live with an experimental brain implant 
Early BCI users explain what the technology gives—and takes. (IEEE) 
+ A patient with Neuralink got a boost from generative AI. (MIT Technology Review) 
 
5 Dozens of AI disease-prediction models were trained on dubious data  
A few might already have been used on patients. (Nature) 

6 Uber is breaking from its gig economy model to avoid robotaxi disruption  
It’s spending $10 billion to buy thousands of autonomous vehicles. (FT $) 
 
7 xAI is being sued over data center pollution  
Musk’s AI venture stands accused by the NAACP of violating the Clean Air Act. (Engadget) 
+ No one wants a data center in their backyard. (MIT Technology Review) 
 
8 Apple could win the AI race without running  
It may reap the rewards of everyone else’s spending. (Axios) 
 
9 How 4chan set a precedent for AI’s reasoning abilities  
The notorious forum tested a feature called “chain of thought.” (The Atlantic $) 
 
10 The surprising emotional toll of wearing Meta’s AI sunglasses 
Their shortcomings are making users sad. (NYT $) 
 
 

Quote of the day 

“Everything got a whole lot worse once they rolled out AI.” 

—A copywriter tells the Guardian that they’re drowning in “workslop” — AI-generated work that seems polished but has major flaws 

One More Thing 

blocks of frozen carrots and peas

GETTY IMAGES

How refrigeration ruined fresh food 

Bananas may not be chilled in the grocery store, but they’re the ultimate refrigerated fruit. It’s only thanks to a network of thermal control that they’ve become a global commodity. And that salad bag on the shelf? It’s not just a bag but a highly engineered respiratory apparatus. 

According to Nicola Twilley—a contributor to the New Yorker and cohost of the podcast Gastropod—refrigeration has wrecked our food system. Thankfully, there are promising alternative preservation methods.  

Read the full story on her research. 

—Allison Arieff 

We can still have nice things 

A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.) 

+ Spotify only shows 10 popular songs per artist. This tool lists them all. 
+ These GIF animations are mesmerizing loops of nostalgia. 
+ This site beautifully visualizes Curiosity’s 13 years on Mars. 
+ A retro-futurist designer has turned a NES console into a working synthesizer. 

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[Comment] Youth mental health in central Asia: research needs

Little research has been published on mental health difficulties in young people (aged 10–24 years) living in central Asia,1 a region comprising Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. As researchers and representatives from academic, non-governmental, governmental, and UN organisations working in Kyrgyzstan and Uzbekistan and beyond, we are noting an increasing number of young people reporting emotional and behavioural symptoms in central Asia in published articles2 and from our own observations.

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Determinants of Digital Health Literacy Among Patients With Serious Mental Illness: Cross-Sectional Survey

Background: Individuals with serious mental illness increasingly use digital devices and the internet to access health information and services but often face challenges when navigating digital tools, which may limit the benefits they receive from online health resources and digital health care services. Objective: The objective of our study was to assess digital health literacy among individuals with serious mental illness and identify factors influencing this literacy. Methods: Participants were recruited, using convenience sampling, from 2 psychiatric clinics, 1 day-care center, and 4 halfway houses in Taipei, Taiwan, between May 2024 and February 2025. Self-reported data were collected using a survey that incorporated the eHealth Literacy Scale, the Attitudes Toward Computer/Internet Questionnaire, and the Mobile Device Proficiency Questionnaire. Generalized linear modeling was applied to identify factors associated with digital health literacy. Results: Among 255 participants included in the analysis, 83.5% (n=213) reported owning at least 1 digital device. Digital health literacy was significantly lower among individuals who reported greater perceived difficulty in using digital tools (=−1.533, 95% CI −2.350 to −0.717; <.001) and higher distrust in online information (=−0.986, 95% CI −1.916 to −0.056; =.04). By contrast, greater mobile device proficiency (=0.144, 95% CI 0.008‐0.281; =.04) and self-efficacy (=1.777, 95% CI 0.376‐3.177; =.01) were positively associated with digital health literacy. Conclusions: Despite widespread device ownership, digital health literacy was varied and generally suboptimal among patients with serious mental illness. Perceived difficulty and distrust emerged as major barriers; proficiency and self-efficacy facilitated higher literacy. These findings highlight the need for mental health professionals to integrate tailored digital skills training, confidence-building strategies, and ongoing support into digital health interventions for individuals with serious mental illnesses.
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Pregnancy Sickness Study Identifies New Genetic Links

The University of Southern California (USC) research team that identified the hormone-encoding gene GDF15 as a key driver of pregnancy sickness has identified nine additional genes linked to its most severe form, hyperemesis gravidarum (HG). Six of the identified genes had not been previously linked to the condition.

The Keck School of Medicine of USC team and international collaborators conducted a genome-wide association study (GWAS), scanning the entire genome for differences between women who developed HG during pregnancy and those who did not. They analyzed data from more than 10,000 women with the condition and more than 450,000 controls across European, Asian, African, and Latino ancestries. Their findings offer new clues about the condition and new hope for those affected.

Marlena Fejzo, PhD, a clinical assistant professor of population and public health sciences in the Center for Genetic Epidemiology at the Keck School of Medicine, led the present study and earlier research linking GDF15 to HG. Fejzo told GEN, “The study is much larger than previous studies and on a more diverse population allowing for identification of new genes associated with HG … The new genes give us new directions to explore for prediction, diagnosis, treatment, and response to therapies.”

Fejzo is first author of the team’s published report in Nature Genetics (“Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting”), in which the team stated, “Potential roles for candidate genes in appetite, insulin signaling, and brain plasticity provide pathways to explore etiological mechanisms and therapeutic avenues.”

HG, which affects about 2% of women, causes nausea and vomiting so severe that eating can become extremely difficult. “Most pregnancies are affected by nausea and vomiting (NVP), but in 0.3–10.8% of pregnancies the symptoms can be severe enough to cause maternal weight loss and adverse maternal and fetal outcomes,” the authors wrote. HG in its most severe form can even be life threatening.

HG was long misunderstood and often dismissed as psychological, growing evidence shows that it has a strong biological and genetic basis and can lead to severe malnourishment, putting both mother and baby at risk. Current treatments for HG are frequently ineffective in improving patient symptoms, the authors further pointed out, and so increase the risk of pregnancy termination, postpartum depression, and suicidal ideation, along with other maternal and offspring comorbidities. “Therefore, understanding of HG etiology is critical to begin to address the negative impact severe NVP has on maternal and child health.”

While historical hypotheses have previously centered around human chorionic gonadotropin (hCG), recent large-scale genetic studies have implicated the GDF15 gene encoding growth differentiation factor-15—a hormone associated with nausea and vomiting, the authors further pointed out. Earlier research by Fejzo and an international team had shown that the link between HG and GDF15 lies in women’s sensitivity to the hormone. They found that women exposed to lower levels of the hormone before pregnancy because of a mutation in the gene experience more severe symptoms, while women exposed to higher levels of the hormone before pregnancy have less severe nausea and vomiting symptoms.

“GDF15 was identified as the greatest genetic risk factor for HG in both a genome-wide and an exome-wide association study, and a rare mutation in GDF15 was associated with a greater than tenfold increased risk for HG,” the scientists noted in their newly reported study. Fejzo explained to GEN, “The mutation in GDF15 is rare. People who carry the mutation have abnormally low levels of GDF15 when they are not pregnant and that increases their risk of being hypersensitive to it during pregnancy when it is produced in massive amounts by the placenta.”

Commenting on their prior work implicating a role for GDF15 and HG, Fejzo further explained to GEN, “In our first GWAS study we found the association between the GDF15 gene and HG. Next, we published a whole-exome sequencing study that identified a mutation in GDF15 associated with HG. Then we published our study in Nature which provided strong evidence that hypersensitivity to the rise of GDF15 in pregnancy (due to low pre-pregnancy GDF15 in circulation) is the main driver of the condition.”

For their newly reported study the researchers carried out a multi-ancestry genome-wide association study of 10,974 HG/excessive vomiting in pregnancy cases and 461,461 controls across European, Asian, African, and Latino ancestries from nine contributing studies.

The results identified 10 genes that were linked to HG, including four that had previously been identified, and six new genes. “Because this is the largest study of HG ever conducted, we’ve been able to tease out important new details that were previously unknown,” said Fejzo. “The fact that we’ve studied women from multiple ancestry groups suggests that these results may be generalizable across a broad population.”

The four genes previously identified were growth differentiation factor 15 (GDF15), GFRAL, which produces the receptor for the GDF15 hormone of the same name, and IGFBP7 and PGR, both of which are involved in development of the placenta. The strongest link by far was to GDF15, which rises sharply during pregnancy. “We know that GDF15 and it’s receptor GFRAL are the main drivers and are in a signaling pathway that causes aversions, nausea, and vomiting,” Fejzo told GEN. “More work needs to be done to explore the other associations, but since studies suggest manipulating progesterone and/or IGFBP7 may not be safe in pregnancy, current studies are focusing on the GDF15 pathway.”

The six newly identified genes offer further clues that might help explain the basis of HG or point to new ways of treating it. They include FSHB, TCFL72 SLITRK1, SYN3, IGSF11, and CDH9. “Now that we’ve more than doubled the genes associated with HG, we can dig deeper into the biology behind this condition, as well as new possible pathways for treating it,” Fejzo said. Speaking to GEN, the researchers noted, “Because the new associations are novel, we need to understand the roles they may play in normal pregnancy and then compare that to pregnancies affected by HG.”

Of the newly identified genes, TCF7L2 stands out because it is one of the strongest genetic risk factors for type 2 diabetes and is also associated with gestational diabetes. “This is a brand-new target, and it’s not yet clear what it’s doing in pregnancy,” Fejzo said. In further commentary to GEN, Fejzo added, “The TCF7L2 gene is a type 2 diabetes-associated gene and a transcription factor that may control glucagon-like peptide-1 (GLP-1) expression and has been associated with liraglutide effects resulting in greater weight loss in obesity. So understanding its role in that rapidly evolving therapeutic arena has potential.”

Several of the other genes identified are involved in appetite and nausea, as well as brain plasticity, or how the brain learns and adapts to new information. Fejzo suggests the brain may learn to associate certain foods with feeling sick, leading to strong, lasting aversions during pregnancy. More research is needed to explore this possibility. “Other genes are associated with learning flexibility so we hypothesize that they may play a role in conditioned taste aversion and may provide new targets to alter or dampen learned aversions,” Fejzo told GEN. Historically, people believed the pregnancy hormone hCG was the cause, but we found no evidence to support that and instead, fascinatingly, we found a link to the follicle stimulating hormone receptor.”

Of the ten candidate genes six—GDF15, GFRAL, IGFBP7, PGR, TCF7L2 and SYN3—have been linked with cachexia—a wasting condition with similar symptoms to HG, including loss of appetite, weight loss and muscle wasting, the scientists noted. “Manipulation of GDF15, GFRAL, IGFBP7, PGR and TCF7L2 in animal models has shown effectiveness in reducing symptoms of cachexia. Thus, assuming analogous functions for these factors in HG, there is both genetic and biological support for causal and potentially reversible contributions for these genes in NVP.”

The researchers also found that some genes linked to HG were associated with other pregnancy outcomes. “This study also identified individual associations between risk genes and adverse outcomes including shorter pregnancy duration, pre-eclampsia, and birth weight,” they noted.

Several medications are available for treating HG, but even the most effective, Zofran, only partly relieves symptoms for about half of patients. The new findings reveal new potential treatment targets and could possibly also help match existing medications to patients based on their genetic profiles. “The ten genetic associations provide intriguing avenues to advance our understanding and pursue therapeutic pathways for a common pregnancy condition that in its most severe form is associated with substantial morbidity and even mortality for mothers and exposed offspring,” the scientists concluded.

Fejzo and her team just received approval to launch a clinical trial of metformin, a widely used diabetes medicine that increases GDF15 levels. The study will test whether taking metformin before pregnancy can desensitize women to the hormone, potentially reducing nausea and vomiting or preventing HG in women who have had it before. GEN was told, “We will be initiating a clinical trial to increase GDF15 prior to pregnancy in patients with a history of HG and planning to conceive to desensitize them to the hormone’s rapid rise in early pregnancy. We and others have shown preliminary evidence that this approach may work as in our retrospective study pre-pregnancy metformin use was associated with a significant reduction in HG risk.”

The post Pregnancy Sickness Study Identifies New Genetic Links appeared first on GEN – Genetic Engineering and Biotechnology News.

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Cancer Cell Apoptosis Avoided by Membrane Oligomerization

Apoptosis in cancer cells may be easier to unleash than previously thought, according to new research led by scientists at Umeå University and collaborators. That finding could open up more cancers to treatment with anti-apoptotic drugs. The team used neutron reflectometry (NR) and ATR-FTIR to detail communication between proteins in and around the mitochondrial outer membrane (MOM). 

“We use neutrons as a kind of ‘x-ray’ magnifying glass to study how various proteins talk to each other inside the cell,” Gerhard Gröbner, PhD, told Inside Precision Medicine. He is a professor at Umeå University and senior author of a new study that looks at the role of the Bax protein in apoptosis. The findings appear in ACS Chemical Biology.

Apoptosis is a form of programmed cell death that removes old or damaged cells, enabling the immune system to function properly. When apoptosis does not work as it should, as in many cancers, cells can divide uncontrollably and form tumors.

Many cancer therapies (e.g. drugs and radiation) are designed to trigger apoptosis in tumors. But there are also many aggressive and often incurable cancers that current anti-apoptotic therapies do not work on due to these tumors’ intensive use of survival proteins, such as Bcl-2 and its relatives, which can stop apoptotic death.

“Finding new drugs to inhibit Bcl-2 and its relatives in a wider sense would thus help treat more cancers. Currently only one Bcl-2 drug is available, and it is used for very specific leukemia,” said Gröbner.

“Going forward we will test a range of potential drug candidates to block Bcl-2 to release cell-killing proteins like Bax again to improve therapies,” he added.

The cell‑killing protein Bax protein is one of the most important proteins controlling apoptosis. Once activated, Bax can initiate apoptosis by forming pores in the membranes of mitochondria. Another key protein from the same family, the cell‑protective protein Bcl‑2, instead prevents Bax from killing tumor cells. In nearly half of all human cancers, one of the underlying problems is an increased production of Bcl‑2, which promotes tumor growth and often leads to poor response to therapy.

“In our research, we have used advanced neutron experiments to show how Bcl‑2 protects cancer cells by blocking the death‑inducing proteins that are most often activated by therapy,” said Gröbner.

The team used NR and ATR-FTIR to elucidate the molecular communication between those proteins in and around the mitochondrial outer membrane (MOM). The spatial and temporal changes across model MOM surfaces were resolved during the interaction of Bax with Bcl-2. The NR-derived membrane surface Bax distributions suggested that Bcl-2 mediated Bax sequestration through both Bcl-2/Bax heterodimerization and Bax/Bax oligomerization. Kinetic analysis revealed a two-step process: rapid formation of Bcl-2/Bax heterodimers, followed by slower Bax oligomerization on these complexes

The experiments show that Bcl‑2 can capture and bind several Bax proteins at the same time. This makes the inhibition of cell death more efficient than previously thought. Cancer cells do not need to produce extremely large amounts of Bcl‑2 to protect themselves—even a moderate increase can be sufficient.

The researchers also investigated how the composition of the mitochondrial membrane affects the interaction between the proteins. They found one particular lipid, cardiolipin, can promote apoptosis and help Bax form pores in the membrane. However, even in membranes containing cardiolipin, a sufficiently high level of Bcl‑2 can still prevent cell death.

“In the longer term, this type of knowledge could open up new opportunities for cancer treatment, for example by targeting Bcl‑2 and its protective function,” says Gröbner.

The study was carried out in collaboration between researchers from Umeå University, Lund University, the European Spallation Source (ESS) in Lund, the ISIS Neutron and Muon Source and Diamond Light Source in the United Kingdom, and the Institut Laue‑Langevin (ILL) in France.

 

The post Cancer Cell Apoptosis Avoided by Membrane Oligomerization appeared first on Inside Precision Medicine.

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Pivotal Phase III Pancreatic Cancer Trial Advances RAS-Targeting Daraxonrasib

This week, Revolution Medicines (RevMed) announced positive topline results from its global Phase III trial of RAS-targeting daraxonrasib in metastatic pancreatic ductal adenocarcinoma (PDAC) patients. In RASolute 302, patients on daraxonrasib showed improvements in progression-free survival (PFS) and overall survival (OS) compared with standard of care cytotoxic chemotherapy.

“With these unprecedented results, daraxonrasib has the potential to achieve our goal of bending the mortality curve in pancreatic cancer. Unlike chemotherapy, daraxonrasib is a RAS-targeted medicine that targets RAS in its active ‘ON’ state, shutting down a key signaling pathway that drives aggressive tumor growth. This is especially important in pancreatic cancer, which is among the most RAS-driven cancers, with more than 90% of tumors harboring a RAS mutation that is the driver of the cancer,”  Mark A. Goldsmith, MD, PhD, told Inside Precision Medicine. He is chief executive officer and chairman of Revolution Medicines.

Daraxonrasib patients achieved a median OS of 13.2 months versus 6.7 months for chemotherapy. The drug was generally well tolerated, with a manageable safety profile and with no new safety signals.

RAS is the key oncogenic driver of pancreatic cancer. Nearly all RAS mutations occur at KRAS position G12, but RAS mutations in other isoforms and at KRAS positions G13 and Q61 are also observed.  

RevMed now intends to submit the drug for approval by regulatory authorities, including the U.S. Food and Drug Administration as part of a future New Drug Application, and for presentation at the 2026 American Society of Clinical Oncology Annual Meeting. Information about current trials of the drug are available at  https://revmedclinicaltrials.com/.

“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” said Brian M. Wolpin, MD, MPH, professor of medicine at Harvard Medical School, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial. “The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy. I believe that this new approach is a very important advance for the field that I expect will be practice-changing for physicians and improve the care for patients with previously treated metastatic pancreatic cancer.”

Pancreatic cancer is the most RAS-addicted of all major cancers, with more than 90% of patients harboring tumors driven by mutations in RAS proteins. These mutations span a range of RAS variants that fuel aggressive tumor behavior. Daraxonrasib, a multi-selective inhibitor of RAS(ON) proteins, is the first investigational agent in a novel class of RAS inhibitors designed to address a diverse and broad spectrum of oncogenic RAS drivers.

The RASolute 302 trial enrolled patients with pancreatic tumors harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as those without an identified RAS mutation. The primary endpoints of the trial were PFS and OS in patients with tumors harboring RAS G12 mutations. Secondary endpoints assessed PFS and OS in all enrolled patients (the intent-to-treat population), including those with tumors with and without (wild type) an identified RAS mutation.

Daraxonrasib is an oral RAS(ON) multi-selective, non-covalent inhibitor. Cancers driven by a broad range of common RAS mutations include PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. The drug is currently being evaluated in four global Phase III registrational trials, including three in PDAC and one in NSCLC.

Daraxonrasib works by suppressing RAS signaling through inhibition of the interaction between both wild-type and mutant RAS(ON) proteins and their downstream effectors.

Pancreatic cancer is one of the deadliest malignancies, because of its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that each year approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from it.

The post Pivotal Phase III Pancreatic Cancer Trial Advances RAS-Targeting Daraxonrasib appeared first on Inside Precision Medicine.

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Fact-Checking Large Language Model Responses to a Health Care Prompt: Comparative Study

Background: Large language models use machine learning to produce natural language. These models have a range of potential applications in health care, such as patient education and diagnosis. However, evaluations of large language models in health care are still scarce. Objective: This study aimed to (1) evaluate the accuracy and efficiency of automated fact-checking by 2 large language models and (2) illustrate a process through which a large language model might support a patient in redrafting a prompt to include key information needed for patient safety. Methods: A parallel comparison of 2 large language models and 3 human experts was conducted. A clinical scenario was devised in which a woman aged 23 years questions the safety of retinoid treatment for acne by sending prompts to 2 large language models (GPT-4o and OpenBioLLM-70B). GPT-4o and OpenBioLLM-70B were asked to suggest improvements to the patient’s initial prompt to elicit key information for clinical decision-making. After the patient sent the revised prompt to the large language models, the models were then asked to fact-check the final response. To test the generalizability of automated fact-checking, a set of 20 clinical statements on disparate topics, mostly related to drug indications, contraindications, and side effects, was developed. The large language models also fact-checked these 20 medical statements. The results were compared against the evaluations of 3 clinical experts. The outcome measures were as follows: (1) percentage of accuracy of automated fact-checking, (2) time to complete fact-checking, and (3) a binary outcome for prompt redrafting (advising the patient to revise her prompt by naming her acne medication to address safety concerns). Results: For the scenario of a patient with acne, GPT-4o and OpenBioLLM-70B both had 86% agreement with the clinical experts’ fact-checking. The large language models did not consistently convey the urgency of discontinuing isotretinoin treatment when pregnancy is suspected. In addition, the models did not adequately convey the importance of folic acid supplementation during pregnancy. For the set of 20 medical claims, GPT-4o fact-checking had 100% agreement with that of human experts, whereas OpenBioLLM-70B had 95% agreement. OpenBioLLM-70B diverged from human experts and GPT-4o on 1 question related to pediatric use of antihistamines. The expert fact-checks took a mean time of 18 (SD 3.74) minutes, GPT-4o took 42 seconds, and OpenBioLLM-70B took 33 minutes. The GPT-4o responses for the acne scenario had some inconsistencies but zero fabrication and no obvious omissions. In contrast, OpenBioLLM-70B omitted 1 key information item needed for patient safety. Conclusions: GPT-4o can interact with patients to improve the quality and comprehensiveness of the information contained in health-related prompts. GPT-4o and OpenBioLLM-70B can conduct efficient fact-checking that is close to the level of accuracy of human experts. Human experts need to perform additional checks for accuracy and safety.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/35585a0a05dacf1d0cdf467d36579925" />

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Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer

A randomized Phase II trial offers a rare signal of progress in pancreatic cancer, a disease long marked by therapeutic stagnation, with investigators reporting that the experimental agent elraglusib (9-ING-41) improved survival when added to standard chemotherapy of gemcitabine plus nab-paclitaxel (GnP).

Published in Nature Medicine, the study evaluated the novel drug—developed within an academic setting at Northwestern University—in patients with metastatic pancreatic cancer. The findings suggest that targeting glycogen synthase kinase-3 beta (GSK-3β), a protein not previously exploited clinically in this disease, could open a new therapeutic avenue.

“This is one of the first trials in a randomized setting that has been positive in pancreatic cancer in the last decade,” said Devalingam Mahalingam, MD, PhD, a study leader at Northwestern University. “There was really a barren spell… many failed trials. So it’s nice to see a positive trial.”

A modest but meaningful survival gain

The multicenter trial enrolled 233 patients across North America and Europe, randomly assigning them to receive chemotherapy alone or in combination with elraglusib. Patients receiving the combination lived a median of 10.1 months compared with 7.2 months for chemotherapy alone, and the addition of elraglusib reduced the risk of death by 38%.

Perhaps more striking, survival at one year doubled in the experimental arm (44% vs. 22%), and approximately 13% of patients remained alive at two years—an uncommon outcome in metastatic pancreatic cancer.

Mahalingam emphasized that the benefit was not necessarily reflected in higher tumor response rates. Instead, patients appeared to derive prolonged disease control.

“We didn’t really see much more tumor shrinkage compared to chemo alone,” he said. “But patients stayed on the treatment arm longer… sometimes they would reduce or drop the chemo and just stay on the drug.”

This pattern, he added, points toward a mechanism beyond direct cytotoxicity.

A different mechanism of action

Unlike conventional chemotherapy, which primarily targets rapidly dividing cells, elraglusib appears to act on the tumor microenvironment—the complex ecosystem of immune cells, stromal tissue, and signaling molecules surrounding cancer cells.

The drug inhibits GSK-3β, a protein involved in multiple cellular processes, including metabolism, signaling pathways, and immune regulation. While broadly expressed in normal tissues, GSK-3β can be co-opted by tumors to promote growth and suppress immune responses.

“GSK-3 beta is expressed in many tumors,” Mahalingam said. “It’s part of a central regulator of normal cell functioning… but in cancer, this pathway is used to allow for tumor growth and proliferation.”

Preliminary analyses from the trial suggest that elraglusib may enhance antitumor immunity. Biopsies and blood-based markers indicated changes consistent with immune activation, supporting the hypothesis that the drug helps re-engage the immune system in a tumor type typically resistant to immunotherapy.

“We saw what we call immunomodulatory effects,” Mahalingam noted. “The immune cells might be driving some of the survival benefit we see.”

This is particularly notable given the long-standing failure of checkpoint inhibitors in pancreatic cancer, a tumor characterized by a highly immunosuppressive microenvironment.

Developed in academia

Elraglusib’s development trajectory also sets it apart. The compound originated in academic laboratories more than a decade ago, with early work spanning Northwestern University, the University of Illinois Chicago, and the Mayo Clinic.

“This is what not many drugs are—developed within an academic setting,” Mahalingam said. “It was founded in a chemistry lab… and then moved into a spin-off company to raise funding for trials.”

After preclinical development between 2010 and 2015, the drug entered early-phase trials around 2017 and has since been evaluated across multiple tumor types, with a recent focus on pancreatic cancer.

The randomized Phase II trial marks the first time a GSK-3β inhibitor has demonstrated efficacy beyond early-stage testing.

Broad eligibility, real-world relevance

Investigators designed the study with relatively broad inclusion criteria, enrolling patients with high tumor burden and poor nutritional status—characteristics common in real-world pancreatic cancer populations but often excluded from clinical trials.

“We allowed patients with very large volumes of disease,” Mahalingam said. “We did not restrict patients for albumin… we didn’t engineer the study to look better.”

This approach may partly explain the modest median survival difference, as some patients progressed too quickly to benefit. However, it also strengthens the generalizability of the findings.

Safety and next steps

Side effects associated with elraglusib were generally manageable and consistent with chemotherapy, including hematologic toxicities, fatigue, and reversible vision changes.

The next step will be a confirmatory Phase III trial, with discussions ongoing with regulators.

“We really need to confirm the studies in a large phase three trial,” Mahalingam said, adding that trial design considerations include how to integrate emerging therapies such as KRAS inhibitors.

Investigators are also exploring combination strategies, including pairing elraglusib with immunotherapy or alternative chemotherapy regimens. Early safety studies suggest such combinations are feasible, though efficacy data remain limited.

Potential beyond pancreatic cancer

Given the central role of GSK-3β in multiple cellular pathways, researchers are already investigating the drug’s potential in other malignancies, including hematologic cancers and pediatric tumors such as Ewing sarcoma and medulloblastoma.

“This is a new class of potential cancer therapeutics,” Mahalingam said. “Certainly, there would be excitement in seeing where this target can be applied to other tumors.”

While challenges remain, the trial’s results offer cautious optimism in a field where progress has been incremental at best.

“Even if it means that this class of drugs can be used for future drug development,” Mahalingam said, “it gives an opportunity to expand therapeutic potential—not just for pancreatic cancer, but beyond.”

The post Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer appeared first on Inside Precision Medicine.

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Public Perceptions of AI in Medicine and Implications for Future Medical Education: Cross-Sectional Survey

Background: The integration of artificial intelligence (AI) into clinical practice is contingent on public trust. This trust often depends on physician oversight, yet a significant gap exists between the need for AI-competent physicians and the current state of medical education. While the perspectives of students and experts on this gap are known, the views of the US general public remain largely unquantified. Objective: This study aimed to assess US public perceptions regarding AI in medicine and the corresponding emergent needs for medical education. We specifically sought to quantify public trust in different diagnostic scenarios, concerns about physician overreliance on AI, support for mandatory AI education, and priorities for the future focus of medical training. Methods: We conducted a cross-sectional, web-based survey of adults in the United States in November 2025. Participants (N=524) were recruited via SurveyMonkey Audience. We calculated descriptive statistics, frequencies, proportions (percentages), and 95% CIs for all main survey items. Results: A total of 524 participants completed the survey. Most (n=329, 62.8%; 95% CI 58.6%‐66.9%) placed the most trust in a physician’s diagnosis based on their expertise alone; only 7.8% (n=41; 95% CI 5.5%‐10.1%) trusted an AI-first diagnostic model. Trust was highly contingent on training: 93.9% (n=492) of participants rated formal physician training on AI limitations as “essential” or “very important.” Widespread concern about physician overreliance on AI was reported, with 81.1% (n=425) being “very concerned” or “extremely concerned.” Consequently, 85.1% (n=446) agreed or strongly agreed that training on AI use, ethics, and limitations should be mandatory in medical school. When asked about future educational priorities, 70.2% (n=368; 95% CI 66.3%‐74.1%) believed that medical education should focus on human-centered skills (eg, empathy and communication) over clinical skills. Conclusions: The US public expressed conditional trust in medical AI, strongly preferring physician-led and critically supervised models. These findings reveal a clear public mandate for medical education reform. The public expects future physicians to be mandatorily trained to appraise AI, understand its limitations, and refocus their professional development on the human-centered skills that technology cannot replace.
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ThermoCas9: Gene Editor Targets Cells with Disease-Related Hypomethylation

Research led by Wageningen University in the Netherlands and the Van Andel Institute (VAI) in Michigan has shown that ThermoCas9, a variant of CRISPR, can distinguish tumor DNA from healthy DNA and selectively cut only the former, marking a potential step toward a highly precise cancer therapy.

The method relies on DNA methylation, a process in which methyl groups are added to DNA to regulate whether genes are on or off. In cancer cells, DNA methylation is altered and can therefore act as a molecular “fingerprint” that differentiates tumor cells from healthy ones.

“ThermoCas9 is the first CRISPR-associated enzyme to respond to differences in the most abundant type of DNA methylation in human and other eukaryotic cells,” explained co-senior author John van der Oost, PhD, from Wageningen University. “This means we now have a system that we can target specifically toward tumor cells.”

The study, published in Nature, represents the first time a CRISPR-based method has relied on methylation to target human cancer cells.

“ThermoCas9 uses methylation like an address to precisely target cancer cells while leaving healthy cells untouched,” added co-senior author Hong Li, PhD, from VAI. “The findings could be a game changer.”

After analyzing ThermoCas9’s structure and finding that it can distinguish between unmethylated and methylated genes, Li and team introduced the enzyme into different types of healthy human cells with distinct methylation landscapes and into breast and colorectal cancer cells.

They found that ThermoCas9 cut DNA in the tumor cells while leaving healthy DNA intact, suggesting that the system can detect subtle chemical differences between healthy and tumor cells and act on them.

“ThermoCas9 is a perfect example of the value of fundamental research; you have to know how these individual pieces work together,” said Li. “We used biochemistry and structural biology to discover a mechanism that we one day hope will lead to more precise, effective cancer treatment.”

Although the study highlights the potential of ThermoCas9 as a cancer treatment, it does not show that the selective DNA damage it inflicts leads to tumor cell death. The researchers next steps will focus on damaging tumor DNA sufficiently to trigger cell death.

Of note, aberrant methylation patterns also play a role in diseases other than cancer, including autoimmune disorders. It is therefore possible that ThermoCas9 or a similar CRISPR tool could evolve into a versatile molecular strategy that recognizes diseased cells by their chemical “signature” and selectively disables them.

The post ThermoCas9: Gene Editor Targets Cells with Disease-Related Hypomethylation appeared first on Inside Precision Medicine.