STAT+: Flawed study on the antidepressant Paxil came with a cautionary note — if you knew how to find it

File this under “hiding in plain sight.”

Last fall, the Journal of the American Academy of Child & Adolescent Psychiatry issued a so-called expression of concern about a controversial study that was published in 2001 about the widely prescribed antidepressant known as Paxil.

Such a step is taken when a study may have errors or include unreliable information. The notice, which followed a request for a retraction, indicated that a review was underway. Meanwhile, it served as a warning, of sorts, to health care providers who might consult the study when deciding whether to prescribe the medicine.

Continue to STAT+ to read the full story…

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

MIT Technology Review Explains: Let our writers untangle the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here.

Just before Artemis II began its historic slingshot around the moon, Jared Isaacman, the recently confirmed NASA administrator, made a flurry of announcements from the agency’s headquarters in Washington, DC. He said the US would soon undertake far more regular moon missions and establish the foundations for a base at the lunar south pole before the end of the decade. He also affirmed the space agency’s commitment to putting a nuclear reactor on the lunar surface.

These goals were largely expected—but there was still one surprise. Isaacman also said NASA would build the first-ever nuclear reactor-powered interplanetary spacecraft and fly it to Mars by the end of 2028. It’s called the Space Reactor-1 Freedom, or SR-1 for short. “After decades of study, and billions spent on concepts that have never left Earth, America will finally get underway on nuclear power in space,” he said at the event. “We will launch the first-of-its-kind interplanetary mission.”

A successful mission would herald a new era in spaceflight, one in which traveling between Earth, the moon, and Mars would—according to a range of experts—be faster and easier than ever. And it might just give the US the edge in the race against China—allowing the country to beat its greatest geopolitical rival to landing astronauts on another planet.

While experts agree the timeline is extremely tight, they’re excited to see if America’s space agency and its industry partners can deliver an engineering miracle. “You wake up to that announcement, and it puts a big smile on your face,” says Simon Middleburgh, co-director of the Nuclear Futures Institute at Bangor University in Wales.

Little detail on SR-1 is publicly available, and NASA’s own spaceflight researchers did not respond to requests for comment. But MIT Technology Review spoke to several nuclear power and propulsion experts to find out how the new nuclear-powered spacecraft might work.

Nuclear propulsion 101

Traditionally, spaceflight has been powered by chemical propulsion. Liquefied hydrogen and liquefied oxygen are mixed, and then ignited, within a rocket; the searingly hot exhaust from this explosion is ejected through a nozzle, which propels the rocket forth.

Chemical propulsion offers a significant amount of thrust and will, for the foreseeable future, still be used to launch spacecraft from Earth. But nuclear propulsion would enable spacecraft to fly through the solar system for far longer, and faster, than is currently possible. 

“You get more bang per kilogram,” says Middleburgh. A nuclear fuel source is far more energy-dense than its conventional cousin, which means it’s orders of magnitude more efficient. “It’s really, really, really high efficiency,” says Lindsey Holmes, an expert in space nuclear technology and the vice president of advanced projects at Analytical Mechanics Associates, an aerospace company in Virginia. 

The approach also removes one other element of the traditional power equation: solar. Spacecraft, including the Artemis II mission’s Orion space capsule, often rely on the sun for power. But this can be a problem, since it doesn’t always shine in space, particularly when a planet or moon gets in its way—and as you head toward the outer solar system, beyond Mars, there’s just less sunlight available. 

To circumvent this issue, nuclear energy sources have been used in spacecraft plenty of times before—including on both Voyager missions and the Saturn-interrogating Cassini probe. Known as radioisotope thermoelectric generators, or RTGs, these use plutonium, which radioactively decays and generates heat in the process. That heat is then converted into electricity for the spacecraft to use. RTGs, however, aren’t the same as nuclear reactors; they are more akin to radioactive batteries—more rudimentary and considerably less powerful.

So how will a nuclear-reactor-powered spacecraft work? 

Despite operational differences, the fundamentals of running a nuclear reactor in space are much the same as they are on Earth. First, get some uranium fuel; then bombard it with neutrons. This ruptures the uranium’s unstable atomic nuclei, which expel a torrent of extra neutrons—and that rapidly escalates into a self-sustaining, roasting-hot nuclear fission reaction. Its prodigious heat output can then be used to produce electricity.

Doing this in space may sound like an act of lunacy, but it’s not: The idea, and even a lot of the basic technology, has been around for decades. The Soviet Union sent dozens of nuclear reactors into orbit (often to power spy satellites), while the US deployed just one, known as SNAP-10A, back in 1965—a technological demonstration to see if it would operate normally in space. The aim was for the reactor to generate electricity for at least a year, but it ran for just over a month before a high-voltage failure in the spacecraft caused it to malfunction and shut down. 

Now, more than half a century later, the US wants its second-ever space-based nuclear reactor to do something totally different: power an interplanetary spacecraft.

To be clear, the US has started, and terminated, myriad programs looking into nuclear propulsion. The latest casualty was DRACO, a collaboration between NASA and the Department of Defense, which ended in 2025. Like several previous efforts, DRACO was canceled because of a mix of high experimentation costs, lower prices for conventional rocket propulsion, and the difficulty of ensuring that ground tests could be performed safely and effectively (they are creating an incredibly powerful nuclear reaction, after all).

But now external considerations may be changing the calculus. The Artemis program has jump-started America’s return to the moon, and the new space race has palpable momentum behind it. The first nation to deploy nuclear propulsion would have a serious advantage navigating through deep space. 

“I think it’s a very doable technology,” says Philip Metzger, a spaceflight engineering researcher at the Florida Space Institute. “I’m happy to see them finally doing this.”

One version of this technology is known as nuclear thermal propulsion, or NTP. You start with a nuclear reactor, one that’s cooking at around 5,000°F. Then “you’ve got a cold gas, and you squirt cold gas over the hot reactor,” says Middleburgh. “The gas expands, you shoot it out the back of a nozzle, and you have an impulse. And that impulse drives you forward.” 

Because the thrust depends on the speed of the gas being ejected, the propellant gas needs to be light, making hydrogen a popular choice. But hydrogen is a corrosive and explosive substance, so using it in NTP engines can make them precarious to operate. On top of this, NTP doesn’t necessarily have a very long operating life.

Alternatively, there’s nuclear electric propulsion, or NEP, which “is very low thrust, but very efficient, so you can use it for a long period of time,” says Sebastian Corbisiero, the US Department of Energy’s national technical director of space reactor programs. This method uses heat from a fission reactor to generate power. That power is used to electrify a gas and then  blast it out of the spacecraft, generating thrust.  

Both NTP and NEP have been investigated by US researchers, because both have the added benefit of making it easier and safer for human beings to explore the solar system. Astronauts in space are exposed to harmful cosmic radiation, but because nuclear propulsion makes spacecraft speedier and more agile, they’d spend less time in it. “It solves the radiation problem,” says Metzger. “That’s one of the main motivations for inventing better propulsion to and from Mars.”

How to build a nuclear-powered spaceship

For SR-1, NASA has opted for nuclear electric propulsion. NEP is “a much simpler affair” than its thermal counterpart, says Middleburgh. Essentially, you just need to plug a nuclear reactor into a power-and-propulsion system. Luckily for NASA, it’s already got one.

For many years, NASA—along with its space agency partners in Canada, Europe, Japan, and the Middle East—was preparing for Gateway, meant to be humanity’s first space station to orbit around the moon. Isaacman canceled the project in March, but that doesn’t mean its technology will go to waste; the power-and-propulsion element of the nixed space station will be used in SR-1 instead. This contraption was going to be powered by solar energy. It’ll now be attached to an in-development nuclear reactor custom built to survive in space.

What might the SR-1 look like? MIT Technology Review saw a presentation by Steve Sinacore, program executive of NASA’s Space Reactor Office, that offers some clues. So far, the concept art makes it look like a colossal fletched arrow. At the back will be the power-and-propulsion system, while its tip will hold a 20-kilowatt-or-greater uranium-filled nuclear reactor. (For context, a typical nuclear plant on Earth is 50,000 times more powerful, producing a gigawatt of power.) 

Annotated diagram of the key systems of SR-1 Freedom. Indicated at the front is the power and propulsion element, up to 48kw Advanced electric propulsion system. Panels at the middle are high performance, light weight composite and titanium heat rejection system. At the tail there is indicated an advanced closed Brayton cycle power conversion system and a .20kWe Reactor with HALEU UO2 fuel, heat pipe thermal transfer and boron carbide radiation shield. A small attachment at midcraft is labelled. :High Rate Direct to Earth Communications."

NASA

The “fletches” on SR-1 are large fins that allow the reactor to cool down. “You have to have really large radiators,” says Holmes, since the nuclear fission process produces so much heat that much of it has to be vented into space—otherwise, the reactor and spacecraft will melt.

According to that presentation, the spacecraft’s hardware development is due to start this June. By January 2028, SR-1’s systems should be ready for assembly and testing. And by that October, the spacecraft will arrive at the launch site, ready for liftoff before the year’s end. Will the nuclear reactor manage to hold itself together? “Going through the launch safely is going to be a challenge,” says Middleburgh. “You are being shaken, rattled, and rolled.” 

Then, he says, “once you’re up in space, once you’ve got through that few minutes of hell in getting there, it’s zero-gravity considerations you have to worry about.” The question then becomes: Will the mechanics of the reactor, built on terra firma, still work? 

For safety reasons, the nuclear reactor will be switched on around two days post-launch, when it’s comfortably in space. Uranium isn’t tremendously dangerous by itself, but that can’t be said of the nuclear waste products that emerge when the reactor is activated, so you don’t want any of that to fall back to Earth. 

If this schedule is adhered to, and SR-1 works as planned, it’s expected to reach Mars about a year after launch. “It’s an aggressive timeline,” says Holmes, something she suspects is being driven partly by China’s and Russia’s own deep-space nuclear ambitions. The two countries aim to place their own nuclear reactor on the moon’s surface to power the planned International Lunar Research Station—a jointly operated lunar base—by 2035. 

Whether it flies or fails in space, SR-1’s operations should help NASA with putting a nuclear reactor on the moon soon after. “All of the things we’d be learning about how that system operates in space [are] very helpful for a surface application, because basically it’s the same,” says Corbisiero. “There’s still no air on the moon.”

And if SR-1 does triumph, it will be a game-changing victory for NASA. It will also be “a massive win for the human race, frankly,” says Middleburgh. “It will be a marvel of engineering, and it will move the dial in humans potentially taking a step on Mars.” Like many of his colleagues, including Holmes, he remains thrilled by the prospect of the first-ever nuclear-powered interplanetary spacecraft—even with the incredibly ambitious timeline. 

“These are the things that get us up in the morning,” he says. “These are the sorts of things we will remember when we’re old.”

Popular AI Chatbots Can Provide Misleading Medical Information

Around half the outputs from five commonly used artificial intelligence (AI) chatbots could lead users to ineffective or harmful medical choices without professional guidance, suggests research led by the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.

As reported in BMJ Open, the researchers tested the free web versions of Gemini, DeepSeek, Meta AI, ChatGPT 3.5 and Grok available in 2024. They created 50 different adversarial prompts intended to test whether the AI models would give a problematic response or not.

The prompts were intended to realistically represent the kinds of queries members of the public might enter about health topics ranging from cancer to vaccines to stem cells, nutrition, and athletic performance. Some prompts required a specific answer and some were more open.

The researchers collected 250 responses to their prompts and categorized them as non-, somewhat, or highly problematic, using pre-defined criteria. Around 50% were problematic, 30% somewhat problematic and 19.6% highly problematic.  Open-ended prompts received the most problematic answers.

In terms of the specific models, Grok produced a disproportionate share of highly problematic answers, while Gemini produced the fewest highly problematic and the most non-problematic responses. Topic-wise, the chatbots appeared more accurate when asked about cancer and vaccines, but less so when asked about stem cells, athletic performance, and nutrition.

Reference lists provided to users by the models were limited or inaccurate and the answers required some knowledge to interpret properly and were aimed at college-educated users.

“Despite adversarial pressure, chatbots typically responded in a confident, authoritative tone. Refusals to answer and explicit caveats or disclaimers were rare, reflecting the models’ strong tendency to provide an output even when prompts steered toward contraindicated advice,” write lead author Nicholas Tiller, PhD, a research associate at the Lundquist Institute, Harbor-UCLA Medical Center, and colleagues.

“As the use of AI chatbots continues to expand, our data highlight a need for public education, professional training and regulatory oversight to ensure that generative AI supports, rather than erodes, public health,” they conclude.

The post Popular AI Chatbots Can Provide Misleading Medical Information appeared first on Inside Precision Medicine.

The Influence of the COVID-19 Pandemic on Current Teaching Methods, Training, and Perception Among Romanian Surgery-Oriented Students: Cross-Sectional Study

<strong>Background:</strong> The COVID-19 pandemic prompted rapid changes in medical education, accelerating the adoption of online and distance learning methods as alternatives to traditional teaching. While these approaches offered logistical advantages, students worldwide reported significant limitations, particularly in terms of motivation, clinical exposure, and hands-on skill acquisition. Despite the increased use of digital teaching during the pandemic, core educational objectives and the mission of medical training remained unchanged, emphasizing the continued importance of practical experience. <strong>Objective:</strong> This study aims to investigate the impact of the COVID-19 pandemic on current teaching methods in medical education and to explore students’ perceptions of online learning, telemedicine, artificial intelligence, and other modern educational alternatives. <strong>Methods:</strong> This observational, cross-sectional multicentric study surveyed a cohort of Romanian medical students using a self-developed 48-item online questionnaire distributed via social media. Data were collected over 6 weeks (February-March), yielding 451 responses, of which eligible participants included students in clinical years or preclinical students interested in surgical or orthopedic careers, with a heavy representation of the Medicine and Pharmacy University of Timisoara. Statistical analysis was performed using Microsoft Excel and JASP (University of Amsterdam; version 0.95.4). <strong>Results:</strong> A total of 436 responses were analyzed, with students favoring online or hybrid formats for lectures but preferring on-site teaching for practical training. Reduced patient interaction and limited skill acquisition were the main drawbacks of online practical education. Acceptance of hybrid learning correlated with more positive perceptions of teaching methods and a lower perceived desire to cheat. <strong>Conclusions:</strong> The COVID-19 pandemic brought significant changes to the way medicine is being taught in Romania, but it also brought a clearer picture for students and medical staff on how they want medical education to be done. Online cheating remains a significant challenge, but it is being tackled at the moment with different algorithms being tested.

Evaluating the Feasibility of Technology-Based Interventions in Disability and Rehabilitation: Definitions, Considerations, and Dimensions

Technology-based interventions in the field of disability and rehabilitation, which serve assistive, therapeutic, and/or service delivery functions, are considered complex due to the skills required of providers and recipients, degree of individual tailoring, and diversity of use settings. Feasibility studies are an important step in the evolution of complex interventions that can help refine the intervention, inform implementation, and prevent wasted resources. However, guidance is lacking regarding specific considerations for feasibility studies of technology-based interventions in disability and rehabilitation, which leaves researchers and developers reliant on resources from other fields that do not address important technology properties. To advance the field, context-specific definitions, considerations, and evaluation dimensions must be explicitly outlined to ensure that feasibility studies are constructively designed to meet the unique needs of these interventions. In this viewpoint article, we (1) propose a definition and framework for feasibility studies within the specific context of technology-based disability and rehabilitation interventions, (2) highlight important and unique imperatives for feasibility studies of these interventions, and (3) articulate relevant feasibility dimensions and associated evaluation criteria for these interventions. Building on previous work, we distinguish between feasibility studies, wherein we focus on iterative intervention refinement by addressing key development questions (eg, usability), and pilot studies, which are small-scale versions of a larger study that will evaluate intervention outcomes. Integrating previous typologies, we present 13 feasibility dimensions relevant to technology-based interventions and provide sample evaluation criteria, focusing on the intervention itself rather than study design considerations (eg, trial management). This information may be useful for research and development communities (academic, clinical, or industry) to inform comprehensive feasibility studies that examine unique aspects of technology-based interventions to promote real-world impact. This contribution encourages greater harmonization of terminology and evaluation methods to streamline interpretation and comparison across studies.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/ef7cfd105b7f0cb0debd92976a0ac50e" />

User Experience and Early Clinical Outcomes of a Mental Wellness Chatbot for Depression and Anxiety: Pilot Evaluation Mixed Methods Study

Background: Artificial intelligence–powered conversational agents (ie, chatbots) are increasingly popular outlets for users seeking psychological support, yet little is known about how users experience early-stage prototypes or which therapeutic processes contribute to clinical improvement. A transparent evaluation of emerging chatbot prototypes is needed to clarify if, how, and why artificial intelligence companions work and to guide their continued development. Objective: This mixed methods pilot study evaluated user experience, acceptability, and preliminary clinical signals for an early-stage mental wellness chatbot. We also examined whether baseline symptom severity moderated clinical improvement. Methods: Three sequential cohorts (n=125) completed a 2-week, incentivized chatbot exposure (approximately 60 min per week). Participants provided first-impression ratings, qualitative feedback, and pre–post assessments of depressive symptoms (PHQ-8 [Patient Health Questionnaire-8]), anxiety symptoms (GAD-7 [Generalized Anxiety Disorder-7]), psychological distress, well-being, and loneliness. Statistical models estimated symptom change and tested interactions with baseline symptom severity. Mixed methods analysis integrated quantitative outcomes with large language model–assisted qualitative content analysis of open-ended responses. Results: Participants described the chatbot as accessible, easy to use, and emotionally validating, while citing limitations in personalization and conversational depth. Qualitative responses consistently highlighted early therapeutic processes such as emotional validation, goal setting, and perceived attunement. Regression models showed significant pre–post reductions in depressive (Hedges =–0.32) and anxiety (=–0.32) symptoms, alongside modest improvements in distress and well-being. Baseline severity moderated improvement, with marginal effects indicating larger predicted reductions at higher PHQ-8 and GAD-7 baseline scores (eg, PHQ-8=15: =–0.84; GAD-7=15: =–0.62). Conclusions: This pilot provides a comprehensive view of early chatbot development and suggests promising user experiences and preliminary symptom improvements under structured pilot conditions. By integrating experiential and exploratory clinical data, the study identifies candidate process targets to inform ongoing refinement. Findings support continued development and demonstrate procedural feasibility for progression to larger, longer-term trials evaluating engagement and clinical outcomes under more naturalistic conditions.
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Development of Virtual Mental Health Stepped Care Service for a Heart Failure Remote Management Program: Qualitative Descriptive Study

Background: Depression is highly prevalent yet undertreated among people living with heart failure, indicating barriers to mental health services. Although various digital mental health interventions have been developed to detect, treat, and manage depression in this population, these interventions have seen limited integration into clinical care and a lack of implementation research. Stepped care is a service innovation that may promote the implementation of these technologies into clinical settings, but few studies have examined how these services are designed in clinical settings. Objective: This study aimed to identify strategies to address health system barriers to accessing mental health care from the perspective of people living with heart failure, clinicians, and researchers, and to incorporate these strategies into the design of a virtual mental health stepped care service within a heart failure remote management program. Methods: A qualitative description study was conducted using purposive recruitment of people living with heart failure, clinicians, and researchers from a heart failure remote patient management program. As part of a service design approach, semistructured interviews explored potential strategies to address barriers to accessing mental health services. Two researchers coded the data descriptively and constructed themes to guide the development of a virtual stepped care service. Results: A total of 22 participants were interviewed, comprising 13 people living with heart failure and 9 clinicians and researchers. Six themes were identified, comprising 4 requirements and 2 foundational principles. The requirements were to (1) adopt a collective approach to identify distress across methods, people, and time points; (2) maintain a referral-based approach; (3) rely on existing mental health human resources; and (4) offer patient choice among various mental health care options. These requirements were supported by two principles: (1) building on organizational strengths and (2) reducing treatment burden. Based on these findings, a virtual stepped care service was developed, incorporating a depression screening module, referral-based workflows, and, where clinically appropriate, patient choice in treatment selection. Conclusions: The stakeholder-informed design of this virtual stepped care service contributes to the limited literature on stepped care service design and demonstrates how such models can be tailored to their intended contexts. Although each component was designed to address health system barriers to mental health care for people living with heart failure, resource limitations may constrain the balance between feasibility and quality of care. Future research should evaluate the acceptability of this model among people living with heart failure and clinicians.
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Coverage, Traits, and Geographic Distribution of Online Surgeon Reviews: Large-Scale Cross-Sectional Analysis

Background: The use of online physician rating platforms has significantly increased and has been shown to influence physician selection. There are limited data on the use of these platforms for rating surgeons. Objective: In this study, we sought to assess the geographic distribution of and patterns in rating scores of surgeons in the United States. Additionally, we examined rating volumes across different surgical specialties and the association between peer-nominated and patient-initiated ratings on online rating platforms in the United States. Methods: We conducted a cross-sectional study by identifying 201,154 surgeons in the United States via the National Plan and Provider Enumeration System records and Doctors and Clinicians downloadable file. We assessed surgeon coverage on 3 online rating platforms and their geographic use patterns. We described the rating scores and volumes across different surgical specialties and assessed the relationship between rating platforms by comparing peer-nominated and patient-initiated online ratings. Results: A total of 78.86% (158,630/201,154) of the surgeons had ratings on at least 1 of the 3 patient-initiated websites across 11 specialties. Plastic surgeons, neurosurgeons, and orthopedic surgeons had the highest mean number of patient-initiated ratings. Surgeons with “Top Doctor” recognition from peers (23,171/201,154, 11.52%) were associated with an increased median patient-initiated rating (Healthgrades: 4.36, IQR 3.88-4.71 vs 4.20, IQR 3.64-4.64, <.001, and =0.09; Vitals: 4.30, IQR 4.00-4.60 vs 4.20, IQR 3.80-4.50, <.001, and =0.09; RateMDs: 4.20, IQR 3.80-4.50 vs 3.80, IQR 3.60-4.60, <.001, and =0.16). Geographic analysis indicated that 91.06% (295,816,471/324,870,510) of the US population lives in a county with a surgeon rated 10 times or more. Conclusions: Both patient-initiated and peer-nominated rating platforms have a comprehensive coverage of surgeons in the United States, but this coverage differs significantly between surgical specialties. Further work should assess how publicly available online ratings drive surgeon selection and their association with patient experience and postoperative outcomes.

GLP-1 Drug Improves Liver Health Independent of Weight Loss, Mouse Study Finds

Studying mice, researchers at Toronto’s Sinai Health have found that semaglutide—the active ingredient in popular weight loss drugs that mimic the gut hormone GLP-1—acts directly on a subset of liver cells to improve organ function, and does so independently of weight loss. The finding challenges long-held assumptions about how GLP-1 medicines work in the liver and could reshape how physicians treat metabolic liver disease.

Headed by Daniel Drucker, MD, a senior investigator at the Lunenfeld-Tanenbaum Research Institute, the team reported on their findings in Cell Metabolism, in a paper titled “The weight-loss-independent hepatoprotective benefits of semaglutide are orchestrated by intrahepatic sinusoidal endothelial GLP-1 receptors.”

For years, the liver benefits of semaglutide have puzzled scientists. “Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions,” the authors wrote. The drug was known to lower blood sugar and promote weight loss, but patients’ livers were improving in ways that those effects alone could not explain. And as the authors further noted, “The therapeutic scope of GLP-1 medicines extends beyond glycemic control and weight loss, with benefits evident in people with atherosclerotic heart disease, heart failure with preserved ejection fraction (HFpEF), peripheral artery disease, diabetic kidney disease, knee osteoarthritis, and obstructive sleep apnea (OSA).” However, as the team further pointed out, “… the mechanisms by which GLP-1 medicines improve organ dysfunction remain incompletely understood.”

Drucker has been at the forefront of GLP-1 research since the 1980s when his pioneering discoveries helped lay the groundwork for the development of GLP-1 medicines. After transforming treatment of type 2 diabetes and obesity, semaglutide and other GLP-1 medicines have been approved for other conditions including MASH (metabolic dysfunction-associated steatohepatitis). MASH is a severe form of fatty liver disease in which fat build-up, inflammation, and tissue scarring can lead to cirrhosis and liver failure. It affects about 25% Canadian adults and because it is closely linked with obesity and type 2 diabetes, treatment typically includes lifestyle interventions to reduce weight. “The approval of semaglutide for MASH highlights the importance of understanding the hepatoprotective mechanisms of GLP-1 action,” the investigators stated.

Drucker and colleagues have now found that semaglutide acts directly on the liver to reduce inflammation and scarring and improve organ function in a way that is independent of weight loss. Their finding overturns a prevailing assumption in the field that liver cells do not carry the receptor that semaglutide binds to, meaning the drug had no direct route to the organ.

Postdoctoral researcher Maria Gonzalez-Rellan, PhD, spearheaded the work that combined sophisticated mouse models of MASH with deep molecular analyses of liver cells. Her work identified two cell types carrying semaglutide receptors: liver sinusoidal endothelial cells (LSECs) and immune T cells. Although LSECs account for only about 3% of liver cell volume, they proved to be the key driver of semaglutide’s liver benefits.

A pioneer in GLP-1 biology Dr. Daniel Drucker has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today's widely popular medications for type 2 diabetes and obesity. Dr. Drucker's ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]
A pioneer in GLP-1 biology, Daniel Drucker, MD, has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today’s widely popular medications for type 2 diabetes and obesity. Drucker’s ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]

LSECs line the tiniest blood vessels in the liver and are studded with pores that allow them to act as a molecular sieve, filtering substances passing between the liver and the bloodstream. Gonzalez-Rellan showed that semaglutide reversed MASH in mice that lacked the brain receptors controlling appetite, demonstrating that weight loss is not required for liver benefits. “Unexpectedly. semaglutide improves hepatic inflammation, fibrosis, and immune remodeling through actions on Glp1r+ pericentral liver sinusoidal ECs (LSECs) independent of changes in body weight (BW),” the team reported. “… we leveraged a unique model of GLP-1R deficiency, Glp1rWnt1-/- mice, which are resistant to GLP-1RA-induced weight loss. Remarkably, semaglutide markedly improved hepatic steatosis, fibrosis, and immune remodeling in the absence of weight reduction.”

In a further test, mice lacking LSEC receptors showed no liver improvement on semaglutide even after losing 20% of their body weight. Detailed molecular analyses of liver cell types showed that semaglutide shifts gene activity in LSCEs, prompting them to release anti-inflammatory molecules that act on the broader liver environment, pushing it toward a state more closely resembling a healthy, disease-free liver. “Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health,” the scientists said.

“It turns out that the receptor responsible for these benefits is in a very specialized population of liver cells,” commented Drucker, who is also a professor of medicine at the University of Toronto. “And this receptor orchestrates the production of molecules that talk to many different types of liver cells to calm down the inflammatory environment that is the problem in metabolic disease.”

The findings carry practical implications. GLP-1 medicines have become widely prescribed, yet their mechanism of action in the body, beyond appetite suppression and blood sugar control, have remained incompletely understood. Knowing that semaglutide improves liver health independently of weight loss could influence prescribing decisions. “We’ve seen in clinical trials that patients who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why,” Drucker pointed out. In their paper the team concluded “Hence, semaglutide produces a broad proteomic remodeling of the liver, enabling restoration of metabolic homeostasis and suppression of fibrogenic and inflammatory programs. The strong concordance between single-cell transcriptional changes, bulk tissue proteomics, and biomarker signatures underscores the breadth of GLP-1R-mediated hepatic reprogramming.”

Physicians may choose lower doses that avoid the side effects associated with the higher doses needed for significant weight loss, potentially also lowering costs for patients, Drucker suggested adding “We’re not saying weight loss isn’t important because many things improve when patients lose weight. But we now know that weight shouldn’t be the only measure of success, because GLP-1 medicines will improve liver health whether or not the patient loses weight.”

The post GLP-1 Drug Improves Liver Health Independent of Weight Loss, Mouse Study Finds appeared first on GEN – Genetic Engineering and Biotechnology News.

AACR Warns Congress of Cancer Care Setbacks from Proposed NIH Cuts, Again

Cancer researchers in the United States are once again bracing for a high-stakes funding battle in Washington, as a proposed $6 billion cut to the National Institutes of Health (NIH) for fiscal year 2027 threatens to derail years of scientific progress.

For advocates like Jon Retzlaff, Chief Policy Officer and Vice President for Science Policy and Government Affairs at the American Association for Cancer Research (AACR), the situation feels strikingly familiar and deeply consequential. That sense of déjà vu is shaping the response from the cancer research community, which is now urging Congress to once again reject the administration’s proposal just as it did last year.

To understand the urgency of the current moment, Retzlaff points back to the turmoil of the previous budget cycle. “A year ago, the president had proposed a 40% cut to NIH,” Retzlaff told Inside Precision Medicine. “Things looked pretty bleak.” The consequences were immediate and unsettling: grants were stuck and there were cutbacks on committees and staff.

But Congress ultimately intervened decisively. “We engaged with Congress, who has the power of the purse,” Retzlaff said. “They summarily rejected the president’s proposal for the 40% cuts and instead provided a $450 million increase for NIH.” Lawmakers also delivered a significant boost to the National Cancer Institute (NCI), reinforcing what Retzlaff described as a clear signal of bipartisan support for biomedical research. “What we saw for the current fiscal year… is they summarily rejected the president’s proposal,” Retzlaff said. “So now we are going through the exercise all over again.”

Despite the renewed threat, Retzlaff sees reasons for hope rooted in last year’s outcome. “People asked, ‘How can you be so optimistic?’” He recalled the earlier funding fight. “At least this year, I’m going to be able to tell them why I can be optimistic,” he said. “Because it was Congress that stood up.”

Still, he cautioned against complacency. “We can’t rest on our laurels. We can’t take it for granted,” Retzlaff said. “We will be continuing to press the issue.”

Holding down the precision oncology fort

For AACR, the renewed funding fight underscores a central truth: cancer research depends on long-term, uninterrupted investment. “You need this sustained funding over time,” Retzlaff said. “You go where the science is showing opportunities and also where there might not be opportunities right now.”

He emphasized that scientific progress is rarely linear or predictable. “Even though people can’t necessarily say it’s clear-cut that if we do research in this, we’re going to make some progress,” he said, “for some of the cancers, we just need to do research to try to have that knowledge discovery going on.”

Retzlaff added, “Basic biology is so important,” stressing that foundational science underpins every future breakthrough and the continued growth of precision medicine as the new standard of healthcare. “It’s about identifying the biomarkers that are important,” Retzlaff explained.

Meanwhile, emerging areas such as cancer vaccines are generating both excitement and urgency. “Cancer vaccines are now a big issue,” he said. “AACR is very interested in pushing that kind of research forward.”

Yet all of this progress depends on stable funding. Without it, Retzlaff warned, research priorities could narrow dangerously. “If you start cutting back, the next thing you know, we’re just funding breast cancer and lung cancer,” he said, “whereas the rare cancers need to be investigated. We need to give those people hope.”

Sustained national commitment to health

Funding cuts would also ripple through the clinical research pipeline. Retzlaff, who has become more involved in clinical trials in recent years, noted their complexity and cost.

While pharmaceutical companies often support later-stage development, early and exploratory studies depend heavily on NIH funding. “We rely on pharmaceutical companies… once you get into the translational part,” he explained, but without federal investment at the front end, fewer discoveries will ever reach that stage.

For AACR, protecting NIH funding is about more than preserving scientific momentum; it’s about sustaining a national commitment to health. “We’ve got 50,000 members,” Retzlaff said. “Two-thirds of them are from the U.S., and probably two-thirds of them are completely reliant in many ways on NIH funding.” That dependence drives the organization’s advocacy efforts. “Our number one priority is inspiring excitement on Capitol Hill and from lawmakers for robust, sustained and predictable funding for the NIH,” he said.

AACR’s outreach spans everything from congressional briefings to large-scale advocacy events. “It’s working with the entire community,” Retzlaff said, noting collaborations with hundreds of organizations and initiatives, such as Medical Research Hill Day. “We’re constantly looking at drum[ming] up conversations with the media,” he added. “It’s things like that—briefings, reports, letters—you name it.”

At the same time, AACR is navigating broader policy and public health challenges. Retzlaff highlighted ongoing engagement with the Food and Drug Administration (FDA) on issues ranging from clinical trial efficiency to tobacco regulation.

Backing cancer vaccines

Prevention, too, remains a critical priority. “HPV prevention is very important,” he said, though he acknowledged that misinformation has slowed progress. “The anti-vaccine movement is a huge concern.”

Retzlaff said that the cancer vaccine issue is rooted in communication and not the regulators. According to Retzlaff, the director of the National Cancer Institute has had some meetings with Secretary Kennedy, who was supportive of moving cancer vaccines forward. “We have to figure out what it is that people will accept about cancer vaccines that they’re not accepting about vaccines overall,” Retzlaff said. “That’s a communication issue… trying to combat the misinformation out there.”

AACR has even debated trying new names for the modality. Retzlaff elaborated, “There was some discussion about whether we can change the name of this from ‘cancer vaccines’ to something else.”

As Congress weighs the proposed cuts, AACR is calling on researchers, patients, and advocates to speak out once again. The message, Retzlaff said, is simple but urgent: “We definitely want to get the information out… about the importance of NIH medical research… and inspire people to take action.”

The outcome will determine not only the trajectory of cancer research but also the pace at which new discoveries can translate into treatments and, ultimately, save lives.

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