Interventions: Behavioral: Acceptance and Commitment Therapy for Moral Injury (ACT-MI); Behavioral: Present Centered Therapy for Moral Injury (PCT-MI)
Sponsors: VA Eastern Colorado Health Care System; Denver Research Institute; Northern California Institute of Research and Education; Henry M. Jackson Foundation for the Advancement of Military Medicine; Palo Alto Veterans Institute for Research
Turmoil at the American Diabetes Association has taken a fresh turn, with leaders blocking editors at its flagship journal from publishing an opinion piece and first-person accounts detailing a high-profile controversy at the group’s own annual meeting just last month.
Nearly five weeks after five diabetes specialists were escorted out of a convention center in New Orleans for handing out reprints of an editorial expressing concern over cuts to federal research, the ADA’s flagship journal, Diabetes Care, was preparing to publish an editorial and several accounts detailing the episode, which drew national attention and prompted the ADA to both apologize for the evictions and pledge a formal review. But the organization says it delayed publication pending the outcome of that review — even as there is disagreement about how it is being carried out.
In the spiked editorial and personal accounts, now available on an open-access website, the diabetes specialists who were ejected in early June detail their treatment. Prominent ADA members, including past leaders and one who resigned in the wake of the confrontation, also express dismay over how the events were handled initially and afterward. All voice disappointment over the decision to suppress views opposing policies of the Trump administration while also disagreeing with how ADA’s leadership handled the episode and its aftermath.
A new paper published in Science describes using artificial intelligence (AI) to design functional synthetic RNA-guided nucleases whose activity matches or exceeds that of natural enzymes. In the paper, titled “Structure and evolution-guided design of minimal RNA-guided nucleases,” the scientists wrote that the results “establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.”
The team includes scientists from Innovative Genomics Institute and the California Institute for Quantitative Bioscience, both at the University of California, Berkeley, and collaborators at other institutions.The findings highlight AI’s ability to expand the CRISPR toolbox to include RNA-guided nucleases with novel properties beyond those found in nature. It is a task that has been challenging for protein design methods because of the complexity of multi-domain proteins, “whose activity depends on coordinated RNA and DNA recognition, activation, and cleavage by distinct conformational states,” the scientists wrote. As such, seemingly small changes can disrupt enzyme activity.
Sequence-based biological language models have been used to successfully design new nucleases by inferring sequence-function relationships, but they often produce versions of these proteins that closely resemble the reference sequences used to train them. Meanwhile, structure-guided rational design approaches, which “offer a robust strategy to sample highly divergent protein sequences” as well as “structures not found in nature” have been used to generate things like dynamic switches and DNA binders. However, designing complex proteins like RNA-guided nucleases with multiple functional domains and conformations has remained challenging for these methods.
In the Science paper, the scientists present an alternate strategy for generating novel functional proteins that combines the ESM Inverse Folding (ESM-IF1) model with evolution-informed residue constraints. As a test case, they used it to generate new variants for TnpB, a family of CRISPR-cas12-like nucleases that mediate RNA-guided DNA cleavage and regulate transcription among other tasks. Members of this enzyme family are “an attractive target for protein design because they couple programmable DNA targeting and a variety of natural functions to a minimal architecture,” the scientists explained in the paper.
The results showed that compared to sequence-based biological language models which generated proteins with binding domains with over 99% identity to natural homology, their approach created “DNA- and RNA-interacting lobes with AI-generated contacts that had 83% and 72% identity to their closest counterparts in nature.”
As part of the study, the scientists screened the activity of the designed proteins, dubbed SynTnpBs, first in the bacterial cells and then selected the most active ones for further testing in plant and human cells. They also used cryo-electron microscopy to determine the structures of the most divergent variants. Their analysis showed that many AI-designed nucleases either retained or surpassed the activity of natural TnpB in multiple cell types. Microscopy studies further revealed that the engineered proteins formed new electrostatic and hydrogen-bonding networks that stabilize interactions at the RNA-DNA interface across different conformations.
Medical experts are divided on Defense Secretary Pete Hegseth’s announcement that U.S. service members will undergo testosterone deficiency screenings with their annual physical exams.
“War fighters aged 30 and older are going to be tested annually as part of their periodic health assessment,” said Hegseth in a video, posted with the caption “The High-T Department of War.” Elective testosterone testing will be available to younger service members, too, and if recommended, testosterone replacement therapy would be at the individual’s discretion.
Results from one of the largest and diverse genetic studies of Parkinson’s disease to date reveal that genetics may play a much greater role in the condition than previously recognized, especially in some ancestries that have historically been underrepresented in clinical studies. Published in The Lancet Neurology, the findings highlight the importance of representative genetic data for the development of targeted treatments that are effective across diverse populations.
Parkinson’s disease is a progressive neurodegenerative condition that affects more than 10 million people worldwide. While decades of research have uncovered key genetic drivers, most cases arise from a complex combination of genetic and environmental factors that can vary widely across populations and individuals.
“The genetic architecture of Parkinson’s disease varies considerably across ancestries, yet most previous genetic studies have focused on individuals of European ancestry,” write the authors of the study, led by Christine Klein, MD, professor of neurogenetics at the University of Lübeck. “This large-scale, multi-ancestry genetic study offers crucial insights into the population-specific genetic architecture of Parkinson’s disease.”
Klein’s team analyzed genome and exome sequencing data from nearly 100,000 individuals across 11 ancestries, using retrospective data from the Global Parkinson’s Genetic Program (GP2). In particular, the study focused on 18 genes with a well-established link to Parkinson’s disease, including both causal and risk variants.
While some genetic contributors were shared across ancestries, the analysis revealed that certain ancestry-specific differences are larger than previously thought. For instance, risk variants of GBA1, the most common across all ancestries, were present in just about 4% of individuals with east Asian ancestry, compared to nearly 53% of those with African ancestry.
The study also identified the first carriers of causal variants in the LRRK2 gene of African ancestries, highlighting the need to include underrepresented populations in large-scale genetic studies. Overall, 2% of Parkinson’s patients were found to carry a single causal genetic variant across 16 genes, ranging from 0.4% among individuals from African ancestry to 10.7% for those with Ashkenazi jew ancestry.
These findings have important implications for ongoing clinical trials evaluating targeted therapies aimed at Parkinson’s patients carrying GBA1 and LRRK2 variants. Without representative data accounting for the broad differences seen across ancestries, precision medicine approaches will fail to be effective for the global population.
Standard genetic screening panels are mainly built using data from individuals of European ancestry, meaning certain variants more common in other populations might end up being overlooked. If key genetic drivers go undetected, patients from underrepresented populations are generally more likely to be locked out of targeted clinical trials evaluating the next generation of Parkinson’s therapeutics.
“Whereas clinical trials targeting GBA1 and LRRK2 variant carriers are primarily performed in Europe and the U.S.A., increased ancestral diversity in Parkinson’s disease research will be crucial to improve diagnostic accuracy, enhance our understanding of disease mechanisms across populations, and ensure equitable application of and access to emerging genetically informed therapies,” Klein and colleagues conclude.
A consortium led by scientists at the Institute for Bioengineering of Catalonia (IBEC) has developed a series of light-activated small molecule drugs that in preclinicial tests restored sight in blind mice. The team’s approach is based on photopharmacology, a technique for reversibly control drug activity using light.
The newly developed compounds, called prosthe6, mimic the function of light sensing photoreceptor cells, which degenerate in blinding diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
The prosthe6 compounds target ON-bipolar neurons and in tests were found to successfully restore saccadic eye movements (optokinetic reflex) in blinded zebrafish larvae, a widely used model for studying visual acuity. Even more strikingly, the researchers demonstrated recovery of innate light-avoidance behavior in mouse models of age-related macular degeneration and retinitis pigmentosa.
Test results suggest that the prosthe6 compounds may be administered by injecting them in the eye, or administered as eye drops. In animal studies the photoswitchable molecules also showed promising preliminary safety profiles, pointing to the development of potential drug candidates for restoring vision in patients with degenerative retinal diseases, without the need for genetic manipulation or implanted devices. Importantly, these compounds are designed to work under normal lighting conditions and do not require light-enhancing devices as optogenetics. They are small, water-soluble molecules that respond to ordinary visible or white light, such as indoor lighting or daylight, without requiring intense or specialized light sources.
“These molecules do not cure blindness, because they do not address the cause of photoreceptor degeneration,” said study co-lead Pau Gorostiza, PhD, ICREA Research Professor at IBEC, leader of the Nanoprobes and Nanoswitches group, member of CIBER-BBN. “But they are remarkably effective at restoring sight, and they do so using a very simple and potentially patient-friendly approach.”
Rosalba Sortino, former PhD student at the University de Barcelona, and currently post-doctoral researcher at Gorostiza’s group at IBEC, added, “Our goal was to restore vision using a molecular mechanism that is as close as possible to how the healthy retina works … Instead of bypassing retinal processing, we aimed to reactivate it right at the same level of the retinal circuit than the lost photoreceptor cells.”
Diseases such as age-related macular degeneration and retinitis pigmentosa affect 200 million people worldwide and are the leading causes of visual impairment and blindness. Beyond the personal impact on quality of life and independence, vision loss places a global economic burden estimated at over US$400 billion per year in healthcare costs and lost productivity.
Researchers Rosalba Sortino (left) and Joaquin Martinez Tambella (right) working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Sortino is a post-doctoral researcher at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC)]
In many of these conditions, photoreceptor (PhR) cells—the retina’s light detectors—progressively degenerate and die. Although the downstream retinal neuronal circuitry remains largely intact and functionally viable, it no longer receives the light signals needed to drive visual processing towards the brain. This opportunity has fueled intense research efforts to develop treatments capable of restoring light sensitivity to the eye. Current strategies include gene therapy—effective only for a very small subset of patients with specific mutations—and electronic retinal prostheses, which are invasive, expensive, and require extensive training for effective use.
More recently, optogenetics and light-responsive drugs have entered clinical testing, the latter with encouraging safety results. “Photopharmacology can develop photoswitchable small molecules to restore vision impairment by conferring light sensitivity to ion channels that are widely expressed in the remaining inner retinal neurons, and a first-in-human clinical trial is ongoing,” the team noted. However, achieving high-quality vision at ambient illumination levels remains a major challenge.
The (IBEC)-led consortium has now developed a new class of photoswitchable small-molecule drugs that are capable of restoring key visual functions in animal models of blindness. The team’s photopharmacology-based technique involves modifying a drug’s chemical structure by adding a light-activated molecular switch, enabling control of the pharmacological action using light. “Unlike (opto)genetic manipulation and surgically implanted retinal electronic prostheses, pharmacotherapy is noninvasive, readily reversible, and can be upgraded when new drugs are approved,” the authors noted. “Medicines are preferred by patients, clinicians, and public healthcare systems, they can be developed and manufactured at lower costs than other approaches and assessed by conventional regulatory procedures and clinical assays.”
The reported work builds on more than a decade of research and was carried out in collaboration with the team co-led by Pedro de la Villa at the University of Alcalá (UAH), as well as researchers from the Institut de Química Avançada de Catalunya (IQAC-CSIC), the University of Barcelona (UB), the Institute Ramón y Cajal of Health Research (IRYCIS), the Autonomous University of Barcelona (UAB), and the Fundació Eduard Soler.
Researcher Joaquin Martinez Tambella working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC)]
The prosthe6 compounds work by acting on a specific type of retinal cells called ON bipolar cells, which normally receive signals from the photoreceptors. “In healthy vision, ON bipolar cells play a key role in passing on information about the presence of light to the rest of the visual circuit,” explained study co-lead de la Villa. “In degenerative eye diseases, although the photoreceptors are lost, much of this underlying circuitry remains intact but inactive. This creates a major therapeutic opportunity.”
By targeting a protein (mGlu6) in this preserved part of the retina, prosthe6 compounds can take over the role of the missing photoreceptors. “… we have targeted metabotropic glutamate 6 (mGlu6) receptors, which are exclusively expressed in ON bipolar cells (OBCs) and localized postsynaptic to PhR cells, thereby leveraging a privileged position to drive physiological visual circuit,” the investigators explained. When light enters the eye, the molecules respond by changing their shape, triggering signals inside the retina in a way that closely resembles natural vision. In this way, the drugs effectively act as “molecular prostheses,” helping the eye process light again without the need for implants or genetic modifications.
Healthy mice naturally prefer to remain in dark environments and instinctively avoid brightly lit areas, a behavior that relies entirely on a functional visual system. Blind mice, by contrast, lose this preference and move indistinctly between light and dark spaces, as they are unable to perceive light. The team showed that after treatment with prosthe6, blind mice once again showed a clear and spontaneous preference for dark areas, indicating that they could perceive light and use this information to guide their behavior.
This recovery occurred without any training and under light levels comparable to those found indoors or on an overcast day, demonstrating that the treatment restores functional light perception capable of driving natural, visually guided behavior.
Two lead compounds, prosthe6-12 and prosthe6-15, showed particularly promising results. The restored behaviors were observed not only after intraocular injection, but also after topical administration as eye drops. “… at least two compounds (prosthe6-12 and -15) appear to be devoid of adverse effects and restore sight by topical administration, which is linked to higher overall clinical success rate than systemic routes for neurological drugs, and to stronger patient adherence,” the investigators pointed out.
The prosthe6 technology is protected by patent and the researchers are now evaluating its safety and formulation to extend the duration of visual rehabilitation. The team is working with Eyelumina, a spin-off company in formation to secure investments that support translational development and future clinical trials.
“Turning this into a therapy is a long and laborious process,” says Gorostiza. “But the results show that there is a realistic possibility of restoring high-quality vision with drugs, non-invasively, reversibly and with a mechanism that is independent of the specific retinal disorder or genetic mutation to reach a majority of patients.”
If successful in humans, the drug-based approach would offer a widely accessible and affordable alternative to existing vision restoration technologies, especially relevant for patients with advanced retinal degeneration for whom no effective treatments currently exist.
In their paper the team further stated, “From a fundamental perspective, prosthe6 constitute new tools for ophthalmology to study the physiopathology of mGlu6 receptors and retinal circuits in vitro and in vivo and contribute to the medicinal chemistry of allosteric modulators. They also achieve the prediction that upstream targeted photopharmacology can deliver nearly native output signals, taking full advantage of the retinal circuit for high-quality vision restoration.”
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.
Meet GPT-Red: an LLM super-hacker OpenAI built to make its models safer
OpenAI has built an LLM super-hacker called GPT-Red that it uses as a sparring partner to help its other models boost their defenses against cyberattacks.
It automates a type of safety evaluation for software systems known as red-teaming, which is typically done by a team of human testers. The aim is to find as many different ways to break or hijack a system as possible.
It feels as if it should be illegal to even think about heating appliances during the height of summer, but we need to talk about heat pumps.
The appliances use electricity for heating, they’re incredibly efficient, and they’re on the rise. In the US, their sales have doubled over the past 15 years, according to a new report. They’re also winning the heating race against fossil fuels, outpacing natural-gas furnaces by 32% during the first quarter of 2026.
These stats are especially striking at this moment, because a key tax credit for heat pumps just ended. So why are heat pumps still so hot? Read the full story for the answer.
This article is from The Spark, our weekly climate tech newsletter. Sign up to receive it in your inbox every Wednesday.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Elon Musk discreetly bought a $1 billion gas turbine firm to power Grok He acquired fossil fuel company APR Energy in May. (Electrek) + The most likely application will be powering AI data centers. (Engadget) + The deal was revealed through an FTC filing. (Gizmodo) + What will power AI’s growth? (MIT Technology Review)
2 A hack shows the Suno AI music generator scraped YouTube, Deezer It scraped decades’ worth of music to train its models. (404 Media) + The hacked is a unique look into the black boxes powering GenAI. (CNET) + AI is coming for music, too. (MIT Technology Review)
3 Thinking Machines has launched an open-weight AI model Inkling offers a US alternative to China’s open-source models. (Reuters $) + It’s the first AI model built by Thinking Machines. (WSJ $) + The startup was founded by former OpenAI CTO Mira Murati. (Axios)
4 Europe is narrowing its ambitions for tech independence Manufacturing and research show promise, but funding is a problem. (NYT $) + Earnings are strong, but an AI gap persists. (Reuters $) + India is also scrambling for AI independence. (MIT Technology Review)
5 Earth is absorbing energy at a rate that’s alarming climate scientists The planet is taking in more heat than models predicted. (Economist $) + The legal case for climate justice is growing. (MIT Technology Review)
6 The AI backlash has tech executives fearing for their lives Violent threats against AI firms are spilling into the real world. (WSJ $) + An anti-AI movement is growing globally. (MIT Technology Review)
7 A Moroccan intelligence insider exposed widespread Pegasus use Including to target journalists, activists, and foreign politicians. (Guardian)
8 AI is powering citizen-led disaster relief from afar for Venezuela It’s helping to locate missing people and coordinate relief. (Rest of World)
9 Thermodynamic computers could turn noise into useful calculations They may offer a cooler, more efficient way to process information. (Quanta)
10 An engineer has explained every ’90s computer in Jurassic Park Fans have debated the technology in the film for decades. (Ars Technica)
Quote of the day
“We hit pause because the communities powering AI should share in its success. Maybe that’s a novel concept in Washington.”
—New York Gov. Kathy Hochul responds on X to President Donald Trump’s criticism of her state’s new data center moratorium.
One More Thing
Will we ever trust robots?
Robotics firm Prosper is developing a humanoid called Alfie to perform tasks in homes, hospitals, and hotels. The company’s founder, Shariq Hashme, has identified trustworthiness as the top design priority—and first hurdle to clear before humanoids can live up to their hype.
Hashme believes one essential tactic to get people to put their trust in Alfie is to build a detailed character from the ground up—something humanlike but not too human. But the robot’s reliance on remote human operators raises broader questions about privacy, labour, and whether society will truly accept humanoids in our private spaces.
It feels as if it should be illegal to even think about heating appliances during the height of summer—seriously, these heat waves in New York have been brutal—but we need to talk about heat pumps.
The appliances use electricity for heating, they’re incredibly efficient, and they’re on the rise. (For what it’s worth, many heat pumps can also be run in reverse to cool buildings.) In the US, heat pump sales have doubled over the past 15 years, according to a new report. And they’re winning the heating race against fossil fuels, outpacing natural-gas furnaces by 32% during the first quarter of 2026.
These stats are especially striking at this moment, because a key tax credit for heat pumps just ended with the close of 2025. But you wouldn’t know it from looking at the data. Why are heat pumps still so hot?
In case you need a quick refresher, heat pumps use electricity to essentially move heat from one spot to another. A refrigerant moves around a loop in the device, expanding and compressing, gathering and releasing heat at different points in the cycle. (For a more in-depth look at the thermodynamics, this explainer I wrote in 2023 still holds up.)
The result is an appliance that can be incredibly efficient. Once you pay for and install a heat pump, it’s generally significantly cheaper to run than a gas or oil furnace or other types of electric heating systems. And because they’re more efficient and don’t involve burning fossil fuels, heat pumps can be a major help in decarbonizing buildings.
One of the major hurdles to wider use of heat pumps is the appliances’ cost: They tend to be more expensive to buy and install than gas furnaces. For this reason, many governments offer incentives to encourage their adoption. In the US, people who installed heat pumps between 2023 and 2025 were eligible for up to $2,000 in tax credits.
Last year, though, the Trump administration slashed those tax credits, along with many of the other incentives that were part of the 2022 Inflation Reduction Act. Effective January 1, 2026, no more financial help for heat pumps.
I think I’ve seen this film before, and I didn’t like the ending. Tax credits of up to $7,500 for new EVs ended on September 30, 2025. In the quarter leading up to that deadline, sales spiked as people rushed to take advantage of the incentive. Then they fell off a cliff. Things are starting to normalize now, but clearly the tax credit’s sunset had a major effect.
But as it turns out, heat pumps are an entirely different story. In the first few months of 2026, sales have actually gone up, as Lucas Davis, an energy economist and UC Berkeley professor, points out in a new analysis.
Heat pump shipments were flat from December to January and have seen a gradual rise since then, according to data from the Air Conditioning, Heating, and Refrigeration Institute, a trade group that represents about 90% of the US market. This increase from winter into spring follows a seasonal trend seen in previous years—and it’s actually a bit stronger in 2026.
This data isn’t what you’d expect to see if losing the tax credit were hurting demand. As Davis lays out in his post, it seems the credit wasn’t really convincing people to install heat pumps, or at least the case for doing so was sufficient without the added incentive.
“It appears that the U.S. market for heat pumps is strong enough that it does not depend on tax credits,” Davis writes.
In 2024, MIT Technology Review put heat pumps on our annual list of breakthrough technologies. “We’ve entered the era of the heat pump,” I wrote at the time.
While heat pump sales have been up and down over the last few years, the era is going strong. The appliances have outsold gas furnaces in the US for the last four years. It’s not just the US, either. Countries including China and Germany have seen strong movement to heat pumps in recent years.
There’s rarely a straight path to adoption for new technology, especially something that requires so many individual households to make a significant change. But it’s encouraging that a major decarbonization tool is going strong, even when roadblocks pop up.
This article is from The Spark, MIT Technology Review’s weekly climate newsletter. To receive it in your inbox every Wednesday, sign up here.
Scientists have identified a compound that could improve the benefits of levodopa treatment for patients with Parkinson’s disease while delaying or preventing side effects that commonly develop with long-term use. The discovery was made at Sinopia Biosciences, a spinout of the University of California San Diego that analyzes large biological datasets to identify novel therapeutic approaches for preventing and managing side effects of existing drugs.
Preclinical findings published today in Science Translational Medicine suggest the drug candidate could significantly enhance the performance of the most effective and widely used treatment for Parkinson’s. If confirmed in clinical trials, the approach could represent a major advancement in the treatment of this increasingly prevalent neurodegenerative condition.
Levodopa can dramatically improve Parkinson’s symptoms, especially during the early stages of the disease. Over time, however, its effects start wearing off between doses, and within five years of treatment, about 40% of patients develop dyskinesia—a complication involving erratic and involuntary movements. Amantadine is currently the only approved drug to treat dyskinesia induced by levodopa, but its psychiatric and vascular side effects significantly limit its use.
“Virtually every Parkinson’s patient takes levodopa,” said Aarash Bordbar, PhD, chief executive officer, chief scientific officer and co-founder of Sinopia Biosciences. “But patients face two major problems with the drug: the reappearance of Parkinson’s symptoms and dyskinesia. There is no drug that can be added to levodopa to address both simultaneously in a robust manner, and that’s what our drug candidate is doing.”
Bordbar’s team analyzed transcriptomics data to understand how levodopa changes gene expression patterns in the striatum, a brain region involved in movement control. The results were compared with a dataset of gene expression changes induced by existing drugs, allowing the researchers to identify compounds that activated the same transcriptional programs responsible for levodopa’s motor benefits while opposing gene expression programs linked to dyskinesia side effects.
“Maximizing clinical benefits of therapeutics while minimizing adverse effects is a central challenge in drug development,” said Bordbar. “By focusing on the pharmacology of an effective drug rather than disease biology alone, the approach prioritizes pathways with demonstrated clinical relevance, increasing translational potential.”
The team identified a promising candidate in trapidil, a drug that has been used for over 50 years in Japan to treat angina. The drug targets PKA-III, a protein involved in movement and dopamine responses within the brain. The researchers then designed a new compound based on trapidil and tested it in mouse and macaque models of Parkinson’s disease.
Results showed that the drug candidate could offer a dual benefit to Parkinson’s patients, simultaneously improving the motor benefits of levodopa while delaying or preventing treatment-related complications—potentially benefiting both long-term users and patients who are newly starting levodopa therapy.
Based on these findings, Bordbar believes there’s a high chance Sinopia’s drug candidate will succeed in clinical trials. This is further supported by the fact the compound is based on a drug that has been safely used for decades. The company is currently completing the toxicology studies required ahead of the first-in-human clinical trial, which is expected to begin next year.
A study by the Alliance for Clinical Trials in Oncology has shown that completing a simple weekly electronic symptom check-in significantly improves quality of life and may reduce health disparities among people undergoing treatment for advanced cancer.
The PRO-TECT study, which is published in JCO Oncology Practice, showed that the biggest improvements occurred among patient groups that have historically faced greater symptom burden or barriers to effective communication with their care team, including Black patients, women, younger patients, and individuals with less formal education.
“Although we know from prior work that systematic symptom monitoring improves quality-of-life outcomes in patients with advanced cancer, the current analysis extends these findings by suggesting that some groups may experience greater benefit,” said first author Allison Deal, MS, a senior biostatistician at the UNC Lineberger Comprehensive Cancer Center.
Study chair Ethan Basch, MD, who is also from the UNC Lineberger Comprehensive Cancer Center explained that the use of remote symptom monitoring using patient-reported outcomes (PROs) in cancer care in increasing across the U.S., with more than 80 health systems and large practices currently implementing this approach. However, he added that “this is still an early time for this patient-centered approach to monitoring patients, and many practices are still learning how best to implement at their own sites.”
For the PRO-TECT study, 1191 adult patients with metastatic solid tumors receiving systemic therapy were randomly assigned to complete weekly electronic symptom monitoring (n=593) or usual care (n=598) for up to one year.
The weekly surveys included questions about symptoms from the National Cancer Institute’s PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) item library, oral intake, patient-reported performance status, and falls. The surveys took a few minutes to complete and patients could choose whether to complete them online (64%) or via telephone-based interactive voice response not requiring Internet access (36%).
If the answers passed a prespecified threshold (i.e., severity or worsening from previous assessment), the participant was sent a link to relevant patient-level materials for self-management of the reported symptom, and a nurse on the participant’s clinical care team was sent an automated email alert.
The researchers report that, during the study, 90% of surveys were completed and 41% of reports triggered an alert.
At three months, participants in the PRO arm had a mean 2.37-point improvement, from a baseline of 77.0 points, in the European Organisation for Research and Treatment of Cancer QLQ-C30 symptom control score, and a mean 1.54-point improvement, from a baseline of 73.9 points, in physical function score.
By comparison, participants given usual care reported a 0.20- and 0.93-point decline in symptom control and physical function, respectively.
Basch noted that the differences between the two arms were statistically significant and clinically meaningful, adding that there were also “substantial delays until symptom worsening” among people in the PRO arm relative to the usual care arm.
Deal and co-investigators also observed significant differences in outcome by race, education level, age, and sex.
Specifically, they found that the improvement in symptom control in the PRO arm was significantly larger in Black patients than in White patients, which essentially erased a baseline gap and brought symptom control among Black patients on par with that among patients by month 3. Black patients were also much more likely to report that the weekly surveys made them feel more in control of their own care and improved conversations with their care team.
Patients with a high school education or less who used the weekly surveys had significantly greater improvements in both symptom control and physical function than those with a college education. They also had higher rates of triggered alerts and reported that the weekly questions felt relevant to their daily lives.
Women and younger patients (<65 years), two groups that traditionally report higher distress and more severe side effects during cancer treatment, experienced substantial quality-of-life gains from the weekly check-ins compared with the usual care group, whereas men and older patients saw no significant improvement relative to usual care.
In addition, the weekly reporting tool was associated with significantly reduced or delayed emergency department visits for patients, which are known to cause financial and emotional stress for patients and their families.
“Our results suggest that remote monitoring may provide underserved cancer patients with a new avenue to communicate concerns that might go underrecognized in routine practice,” Basch told Inside Precision Medicine. “Broad implementation of these systems may represent an effective and highly practical strategy to advance health equity. Future studies should test technology with more general patient audiences.”
He added: “There is a follow-up initiative to this trial called OncoPRO which is supporting health systems across the country as they work to onboard these systems.”
![Researchers Rosalba Sortino (left) and Joaquin Martinez Tambella (right) working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Sortino is a post-doctoral researcher at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC).]](https://www.genengnews.com/wp-content/uploads/2026/07/RSortino-JMartinez-300x223.jpeg)
![Researcher Joaquin Martinez Tambella working in the laboratories of the Institute for Bioengineering of Catalonia (IBEC). Martinez is a PhD student at the Nanoprobes and Nanoswitches group at IBEC and co-first author of the study. [Institute for Bioengineering of Catalonia (IBEC).]](https://www.genengnews.com/wp-content/uploads/2026/07/JMartinez-300x225.jpeg)
