Science, Volume 392, Issue 6798, Page 584-584, May 2026.
Data-driven decisions in a fast-and-loose world
Science, Volume 392, Issue 6798, Page 585-585, May 2026.
Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration
Science, Volume 392, Issue 6798, May 2026.
Ferrimagnetism of ultracold fermions in a multiband Hubbard system
Science, Volume 392, Issue 6798, Page 612-616, May 2026.
Realization of a spin glass in a two-dimensional van der Waals material
Science, Volume 392, Issue 6798, Page 624-628, May 2026.
Digital Therapeutic Content for Substance Use Disorder Treatment: Development and Evaluation Study
Background: Substance use disorders (SUDs) are a major public health concern, contributing to significant individual and societal costs. Despite this, the uptake of evidence-based pharmacologic and behavioral interventions remains limited. The digital delivery of SUD treatment has emerged as a potentially scalable way to reduce access barriers and increase treatment use. Existing digital therapeutic interventions are often created without clinician involvement, evidence-based materials, interdisciplinary input, or content review. The implementation of a structured and methodologically rigorous development process is needed across digital health interventions to help ensure patient-facing materials are validated, understandable, and actionable for the end user. Objective: This early report seeks to describe and evaluate an iterative, interdisciplinary, platform-agnostic process for adapting and refining existing print materials for digital therapeutic modules in SUD treatment. The a priori goal was to evaluate if a structured, human-centered approach would generate digital modules that were rated as understandable and actionable based on a validated assessment for written materials. Methods: Fourteen therapeutic modules were adapted from existing Mayo Clinic–written, patient-facing education materials originally developed by a board-certified addiction psychiatrist and a doctoral-level education specialist for clinical use. A team of 4 purposively recruited licensed alcohol and drug counselors with lived experience with a SUD, all in recovery, and a doctoral-level therapeutic specialist met weekly for one hour over a 6-month period to iteratively adapt this existing content for smartphone delivery (2‐3 hours per module). The process flow included selecting source material, restructuring content for viewing on a phone screen, simplifying language, improving organization and flow to promote understanding, and including specific actions users could take based on the content. The counselors then independently evaluated the modules using the Patient Education Materials Assessment Tool for printable materials (PEMAT-P). PEMAT-P scores for understandability and actionability were calculated as percentages, and descriptive statistics were used to summarize scores in aggregate and across modules. A target of >70% was set for each PEMAT-P domain, consistent with accepted benchmarking standards. Results: Mean understandability and actionability for all modules were 87.2% (SD 4.8%; range 81.4%‐96.9%) and 75.1% (SD 12.3%; range 57.1%‐95.0%), respectively, exceeding the recommended threshold. While all modules were adequately understandable, 35.7% (5/14) scored below the actionability threshold. Conclusions: This early report highlights the value of a human-centered, iterative process for adapting therapeutic materials for digital delivery in SUD treatment. Although the modules performed well overall on PEMAT-P benchmarks, actionability was less consistent than understandability, and aggregate scores masked weaknesses in several individual modules. This indicates that a standardized process does not guarantee actionable material across all content types. Involving current patients in this process may improve the end product by incorporating a perspective that was previously missed.
Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study
<strong>Background:</strong> An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. <strong>Objective:</strong> A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. <strong>Methods:</strong> A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. <strong>Results:</strong> The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. <strong>Conclusions:</strong> A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. <strong>Trial Registration:</strong> Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp
Fraudulent citations, blamed on AI hallucinations, are becoming more common in research papers
Citations in academic papers are intended to ground research in the work that preceded it, over time creating something of a family tree explaining the roots of ideas, protocols, and studies.
But a growing number of these citations lead to dead ends. “Fabricated” citations that do not reference real papers are spreading in the literature, polluting the public record of science, a new study published Thursday in the Lancet shows. Tools using generative AI are likely to blame, say the Columbia University researchers who authored the paper.
Key takeaways from WHO briefing on hantavirus cruise ship outbreak
The MV Hondius, the cruise ship that has garnered global attention because of an apparent outbreak of person-to-person spread hantavirus infections, is on the move. At the request of Tedros Adhanom Ghebreyesus, the World Health Organization’s director-general, Spain has agreed to let the ship dock off Tenerife, in the Canary Islands. The ship is expected to arrive on Sunday.
This outbreak — the first time hantavirus has been suspected of transmitting on a cruise ship — is an evolving situation. It’s also one that is going to take weeks to resolve, because of the long incubation period of hantaviruses. And it could be months before scientists piece together how the virus got on the boat and whether all the subsequent cases were people infected through contact with other people or whether rodents — which are known to carry hantaviruses — that were on board played any part.
Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice
Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.
Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.
Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025.
Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.
The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding.
“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”
Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder.
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