Background: Completion of homework, defined as therapeutic activities assigned between sessions to reinforce skills and promote behavior change, is strongly linked to therapy outcomes. Yet, homework compliance remains low, potentially due to outdated delivery methods such as paper or email. Mobile health technologies may improve engagement by digitizing therapy tasks and tracking progress. Yosa is a mobile health app designed to facilitate homework delivery and enhance engagement between sessions for patients in therapy. Objective: The primary aim of this study was to evaluate the perceived acceptability of Yosa among licensed therapists and individuals currently receiving therapy. A secondary aim was to examine whether key Technology Acceptance Model (TAM) constructs predicted attitudes toward and intention to use Yosa. Qualitative feedback was also collected to inform iterative development and future deployment. Methods: Two cross-sectional surveys were conducted: study 1 with licensed therapists (N=45) and study 2 with current therapy patients (N=96). Participants viewed video demonstrations of Yosa, learned about Yosa’s features, and rated the app on TAM constructs, including perceived usefulness, perceived ease of use, perceived risk, attitude toward, and intention to use Yosa, using 0‐100 scales. For most constructs, higher scores reflected more favorable evaluations, whereas lower perceived risk scores reflected more favorable evaluations. Descriptive statistics and 95% CIs were generated for each construct in both samples, with scores interpreted relative to the neutral midpoint (50). Multiple regression analyses were conducted to examine predictors of attitude and intention to use. Qualitative feedback from the surveys was analyzed thematically. Results: Therapists and patients reported generally favorable perceptions of Yosa across TAM domains. Among therapists and patients, ratings of the perceived usefulness of the homework feature, therapy journal, and overall app; perceived ease of use; attitudes toward Yosa; and intention to use were all above the midpoint. Perceived risk scores were mild to moderate in patients and moderate in therapists, respectively. Regression analyses indicated that perceived usefulness was a positive predictor of both attitude toward and intention to use Yosa across therapists and patients, while perceived risk was negatively associated with these outcomes in several models. Qualitative themes included requests for additional features, usability enhancements, and data privacy concerns. Conclusions: Therapists and patients reported generally favorable perceptions of Yosa after reviewing descriptions and video demonstrations of the platform, particularly in terms of usefulness and ease of use, supporting favorable perceptions of its potential acceptability as a digital tool for between-session therapy support. Qualitative feedback informed refinements aimed at reducing perceived risks and enhancing the intention to use.
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Temporal Patterns of Engagement and Sentiment in a Suicide Prevention Mobile App: Three-Year Observational Study
Background: Temporal fluctuations in distress and suicidal ideation across daily, weekly, and seasonal cycles may influence the use and effectiveness of digital suicide prevention tools. Understanding patterns of app engagement, perceived suffering, and affective expression can inform the design of proactive, personalized digital interventions, thereby impacting adherence and efficacy. Objective: This study aimed to examine temporal patterns of engagement with 2 core components of the suicide prevention app SERO (Suicide Prevention: a Uniform Effort, Resource-Oriented; BFH, Lucerne Psychiatry), specifically the safety plan and the PRISM-S (Pictorial Representation of Illness and Self-Measure—Suicidality) self-assessment, using 3 years of interaction log data, assessing variations across circadian, weekly, and seasonal cycles, and evaluating the sentiment of free-text responses submitted immediately after PRISM-S self-assessments. Methods: We analyzed anonymized interaction logs from the SERO app collected over 3 years (November 2022 to December 2025). Engagement metrics included the frequency of use of the safety planning functionality and PRISM-S self-assessment entries. Free-text responses provided after PRISM-S assessments were analyzed using automated sentiment classification. Temporal analyses examined variations by the hour of the day, day of the week, and season. One-way ANOVAs, post hoc tests, and Pearson correlations were used to examine patterns and associations between perceived suffering and sentiment. Results: A total of 1076 users engaged with the safety planning functionality of the SERO app, generating 3502 entries, with coping strategies and warning signs showing the highest mean interactions and personal beliefs the lowest. Separately, 1212 app users accessed the PRISM-S self-assessment, producing 2329 entries (mean distance 12.91, 95% CI 12.39‐13.42 cm), with most app users recording only 1 or 2 registrations. Safety planning engagement showed clear diurnal patterns, peaking in the afternoon (2 PM to 3 PM) and being lowest at night (midnight to 3 AM), whereas PRISM-S scores were stable across time. Sentiment analysis revealed predominantly negative affect (mean score of −0.41, SD 0.51, 95% CI −0.44 to −0.39), correlated with PRISM-S distance, and was most negative at night (specifically at 11 PM) and during the afternoon (2 PM to 5 PM). Seasonal effects were small but significant for PRISM-S, with the lowest perceived suffering in summer. Conclusions: Digital suicide prevention tools can support routine patterns of coping behavior, but periods of increased reported distress, particularly at night, may be underaddressed. Integrating automated sentiment analysis alongside self-assessments could potentially enable personalized, time-adaptive interventions that detect changes in emotional state and deliver timely, tailored support, thereby strengthening proactive engagement and resilience.
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STAT+: Fresh turmoil roils American Diabetes Association following controversy at conference
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.
Immunotherapy More Effective in Colorectal Tumors with Active DR5 Pathway
Response to cancer therapies is highly variable. While some cancers that have genomic defects, including microsatellite instability (MSI) and deficient DMA mismatch repair (dMMR) are understood to be more likely to activate the immune system, the mechanism underlying this response is still unclear.
Researchers from the Keck School of Medicine of USC have identified a genetic feedback loop in colorectal cancers that may explain one such mechanism. They recently published their work in Gastroenterology.
The team, led by Lin Zhang, PhD, professor and chair of oncology at the Keck School of Medicine, and Heinz-Josef Lenz, MD, associate director for clinical research at the USC Norris Comprehensive Cancer Center, focused on identifying the “role and mechanism of MSI-induced antitumor immunity and immunogenic cell death response.”
To do this, they used a combination of methods including createing a mouse model with transplanted tumor cells, immune cell assays and organoid data to elucidate the mechanism of action for the dMMR derived antitumor immune response.
Mice injected with tumor cells lacking a functional Mlh1, a gene that is involved with DNA repair, showed increased immune response that was tracked for cell signaling, behavior, and gene activity. Researchers identified Death Receptor 5 (DR5) and Ligase 3 (Lig3) as immune response mediators.
“We found that inactivating Mlh1 causes endoplasmic reticulum stress and Dr5–mediated apoptosis in syngeneic colorectal tumors,” the authors wrote. “Sustained immune response against Mlh1-deficient tumors requires nuclear Lig3–mediated release of extrachromosomal circular DNAs from apoptotic cells. A feedback Dr5/Lig3 amplification loop perpetuates apoptosis and immune cell activation in Mlh1-deficient syngeneic tumors.”
This continued immune response to dying tumor cells is critical for effective response to immune checkpoint inhibitor therapy, but it is not the complete story.
“We’ve gathered enough evidence to suggest that this feedback loop is an important piece of the puzzle,” said co-lead author Zhang. “Our hope is that these findings can someday help make cancers more visible to the immune system and more responsive to immunotherapy treatment.”
Validation of these results in humans is a necessary next step to get closer to the clinic. The team analyzed data from human patients, examining gene expression in colorectal cancers. They found that in patients with higher levels of DR5 and Lig3 activity, immune checkpoint inhibitor therapies were move effective at treating the cancer, and those patients were more likely to respond better to treatment.
“One of the most encouraging parts of the study was seeing that the same signals showed up in patient tumors,” Zhang said. “That suggests we’re uncovering a mechanism that could be clinically relevant.”
Moving forward, the team plans to explore the effectiveness of drugs that activate the DR5 pathway and investigate alternative methods for how to incorporate DR5 and Lig3 into personalized colorectal cancer therapies. They also note that, “Our results reveal a functional link between dMMR and antitumor immunity, which may be useful for improving immune checkpoint inhibitor therapy in tumors with different MMR statuses.”
The post Immunotherapy More Effective in Colorectal Tumors with Active DR5 Pathway appeared first on Inside Precision Medicine.
Predicting biotech clinical trials and a new Alzheimer’s drug controversy
On this week’s episode of “The Readout LOUD”: The Kalshi prediction markets are coming for biotech, plus the controversy over an experimental Alzheimer’s disease treatment from Biogen.
Kalshi, the maker of prediction markets, announced this week that it is expanding into biotech. Soon, you’ll be able to make bets on the outcomes of clinical trials and FDA drug reviews. Is that a good thing? We’ll discuss the issues with Jonathan Kimmelman, a bioethicist at McGill University who has researched prediction in clinical trials.
<![CDATA[Oral THC/CBD combo rapidly eases severe dementia agitation in phase 2 trial, with sustained 12-week benefit and similar safety to placebo.]]>
<![CDATA[New review links lithium and Alzheimer disease treatment, fueling calls for biomarker-guided, low-dose clinical trials testing lithium’s multi-target disease-modifying potential.]]>
Sweet Caroline: BCIs That Restore Sensation of Touch Show Long-Term Safety
“Touching hands, reaching out, touching me, touching you.”
The lead up to the chorus of Neil Diamond’s “Sweet Caroline” has become a ritual in stadiums and bars across America, celebrating one of the most universal human experiences: reaching out to touch another person.
For people living with paralysis after a spinal cord injury, that experience often disappears. Damage to the spinal cord not only interrupts movement but also severs the flow of sensory information from much of the body, leaving many unable to feel touch below the site of their injury.
While brain-computer interfaces (BCIs) already restore a measure of independence by translating thoughts into movement, allowing people to control robotic limbs, computers, and other assistive devices, they have long lacked something fundamental: touch. Now researchers report the strongest evidence yet that restoring artificial touch can be done safely over the long term.
In a study published in Science Translational Medicine, scientists followed five people with cervical spinal cord injuries who received tiny electrical pulses directly to the brain’s somatosensory cortex for periods ranging from nearly three years to a decade. Across more than 173 million stimulation pulses delivered over a combined 27 years of implanted use, the researchers found no serious stimulation-related adverse events while consistently restoring sensations of touch to participants’ hands.
One participant in the study described the difference after researchers restored an artificial sense of touch by stimulating his brain.
Instead of merely watching a hand grasp another person’s hand, he said, it felt as though he were shaking it himself. “It’s the difference between ‘I told a robotic arm to shake your hand’ and ‘I am shaking your hand,’” Charles Greenspon, PhD, assistant professor of neurological surgery at the University of Chicago and the study’s lead author, told Inside Precision Medicine. “That degree of embodiment is completely impossible without sensory feedback because you just don’t believe it’s yours.”
Creating touch
That sense of ownership—of a prosthetic becoming part of the body—is one of the biggest remaining challenges in neurotechnology. Companies including Neuralink, Precision Neuroscience, and Paradromics have largely focused on reading signals from the brain. Today’s most advanced BCIs excel at reading neural activity, decoding a person’s intentions to move a robotic arm or computer cursor. But they are largely one-way systems, sending nothing back to the brain.
Without sensory feedback, users must rely almost entirely on vision, making movements slower, less natural, and more mentally demanding. Restoring sensation by writing information back into the nervous system has remained a much greater challenge—not because the concept is new, but because evidence that repeated brain stimulation is safe over many years has been limited.
Although involving only five participants, the study is the largest and longest safety evaluation of intracortical microstimulation in humans. The findings address a major obstacle to the next generation of BCIs: proving that the brain can safely receive artificial sensory information over many years. If confirmed in larger clinical trials, the work could accelerate the development of truly bidirectional BCIs that both decode a person’s intentions and restore the sensory feedback that makes movement feel natural.
The researchers’ approach bypasses the damaged spinal cord entirely. Participants received two tiny microelectrode arrays implanted in the region of the somatosensory cortex responsible for hand sensation. Brief electrical pulses delivered through individual electrodes produced sensations that participants perceived as coming from specific locations on their hands.
“Once that device is in, we deliver tiny electrical pulses to the brain directly, and that creates the sensations,” Greenspon said. “The brain cannot functionally tell the difference between something that occurs at your hand and travels up your arm to the brain or directly stimulates the brain.”
Built to last
The researchers also wanted to know whether the implants would continue working after years of repeated use. Like any implanted medical device, microelectrode arrays gradually degrade.
The results suggest repeated stimulation does not accelerate that process. Detection thresholds increased only gradually, and even after a decade, about 60% of the electrodes in one participant could still reliably evoke touch sensations, while about two-thirds remained functional throughout the study. Researchers also found no relationship between how heavily individual electrodes were used and how quickly they deteriorated. “No company is claiming that these implants last forever,” Greenspon said. “It’s the same as a knee replacement.”
The study’s primary goal was straightforward: determine whether years of repeated stimulation would trigger seizures, damage brain tissue, or accelerate deterioration of the implanted electrodes. Across 623 hours of stimulation, participants experienced no seizures and no serious adverse events related to the stimulation itself.
Researchers also found no evidence that the electrical pulses damaged participants’ remaining natural sensation. The only stimulation-related side effects consisted of 53 brief episodes of lingering tingling or buzzing after stimulation ended, most resolving within seconds. “It’s one of the few times where you want a null result,” Greenspon said. “We just wanted to say, ‘Look, we didn’t find anything bad.’”
That absence of problems may ultimately be the study’s most important finding, providing the evidence regulators and device developers need before sensory feedback can become a standard feature of future BCIs.
Closing the brain’s feedback loop
For people who may eventually rely on BCIs outside the laboratory, restoring touch could prove just as important as restoring movement. Without sensory feedback, every movement requires constant visual attention. Greenspon compares the experience to leaving the dentist after a local anesthetic: “You can speak perfectly… It’s because you don’t know where your tongue is.”
Artificial touch changes something more subtle as well. Rather than operating a machine, users begin to experience a prosthetic as part of themselves. Researchers believe that sense of embodiment could make future prosthetic limbs not only more dexterous but also less mentally exhausting to use.
The next major challenge is restoring proprioception—the internal sense that tells us where our limbs are without looking. Current sensory BCIs cannot reproduce that ability. Researchers also hope future systems will deliver richer sensory information, allowing users to distinguish whether an object is soft or hard, rough or smooth, or beginning to slip from their grasp.
The findings arrive as brain-computer interfaces transition from academic laboratories to commercial development. Before sensory neuroprostheses become routine treatments, researchers will still need to conduct larger clinical studies.
For decades, BCI research has focused on teaching machines to understand the brain. The next generation may depend just as much on teaching the brain to understand the machine. If that happens, the most important advance may not be giving people the ability to control a prosthetic hand. It may be giving them the feeling that the hand is their own.
That is what made the participant’s handshake remarkable. The breakthrough wasn’t that a hand closed around another person’s. It was that, for the first time, it felt like their own handshake.
The post Sweet Caroline: BCIs That Restore Sensation of Touch Show Long-Term Safety appeared first on Inside Precision Medicine.
STAT+: GOP blocks effort to end Medicare test of AI prior authorization
WASHINGTON — A Senate vote to halt a Medicare pilot that uses artificial intelligence to approve or deny care failed along party lines on Thursday.
Republicans voted to block consideration of a Democratic-led measure, which would have stopped the Trump administration from employing prior authorization in original Medicare, where the practice is rarely allowed. The vote was 46 to 50.
The White House had pushed back against the Democratic bill. Medicare officials gave a handout to lawmakers’ offices on Tuesday outlining what they say are the benefits of the test, known as WISeR.
AI-Designed Synthetic CRISPR-Like Nucleases Show Activity in Cells
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.
The post AI-Designed Synthetic CRISPR-Like Nucleases Show Activity in Cells appeared first on GEN – Genetic Engineering and Biotechnology News.