Background: Motivational interviewing (MI) is an effective approach for supporting health behaviorchange, but face-to-face delivery is resource-intensive and difficult to scale. Rule-based conversational agents (CAs) can improve access; however, their scripted interactions and limited language flexibility constrain MI delivery. While large language models (LLMs) are increasingly being used for MI coaching, their conversational fidelity and quality compared with human coaches and rule-based CAs remain understudied. Objective: This study aimed to describe the development of an LLM-based CA, Artificially Intelligent Motivational Interviewing (Aimi), orchestrated with structured workflows, and to evaluate its feasibility, conversational fidelity, and user perceptions during MI coaching interactions. Methods: We developed Aimi using structured LLM workflows designed to enhance MI fidelity. We conducted a within-participants study, where 18 adults interacted with (1) Aimi, (2) a novice MI-trained human coach, and (3) a rule-based CA during live text-based role-play coaching sessions. Transcripts were independently evaluated by an MI expert using the Motivational Interviewing Skill Code, Version 2.0 (MISC-2), to assess MI competency and fidelity. Participants completed a user experience questionnaire to provide general feedback and to assess session alliance, dialogue relevance, empathy, engagement, linguistic quality, and perceived motivation to change. Feedback from users was thematically summarized and categorized under strengths and weaknesses for each approach. Results: Aimi achieved fidelity scores comparable to those of the novice human coach and higher than those of the rule-based CA on summary metrics, including higher reflection-to-question ratios (median 0.84, IQR 0.62-0.92 vs 0.62, IQR 0.42-0.74 vs 0.25, IQR 0.17-0.38), more complex reflections (median 66.67%, IQR 46.97%-76.92% vs 50%, IQR 34.38%-61.88% vs 0.00%, IQR 0%-50%), and greater elicitation of client change talk (median 90.83%, IQR 85.89%-100% vs 73.21%, IQR 63.10%-83.19% vs 66.67%, IQR 57.86%-81.94%). User experience ratings showed no significant differences across conditions. User feedback revealed distinct strengths and limitations across the coaching interactions. Participants described Aimi’s interactions as personalized, fluid, and adaptive, though sometimes overly reflective and lengthy. The novice human coach was viewed as empathetic and supportive but slow to respond, whereas the rule-based coach was viewed as efficient and structured yet limited in depth and personalization. Conclusions: This study demonstrates the technical feasibility of structured LLM-workflows for MI coaching and their capacity to maintain conversational fidelity comparable to that of a novice MI-trained human coach. Given the role-play paradigm, single-rater coding, and small convenience sample, these comparative findings should be interpreted as exploratory. Our findings serve as a foundational baseline for the development of scalable behavior change interventions in clinical settings.
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Structural Biology Reveals New Drug Targets for Rare Neuromuscular Disease
Researchers at the University of California San Diego have uncovered the structural mechanisms that cause congenital myasthenic syndromes (CMS), revealing mutation-specific treatment strategies and identifying an existing antidepressant as a promising candidate for drug repurposing.
The study, published in Nature, explains how disease-causing mutations alter the human acetylcholine receptor (AChR), the protein responsible for converting nerve signals into muscle contraction. The findings also provide a framework for developing precision medicines tailored to the specific mutation carried by individual patients.
CMS is a rare inherited group of neuromuscular disorders that typically appears at birth or early childhood. Mutations in the AChR impair communication between nerves and muscles, leading to muscle weakness, difficulty walking, breathing problems, and, in severe cases, paralysis or death. Although more than 50 disease-causing mutations have been identified, the molecular mechanisms underlying these disorders have remained largely unknown.
To address this question, the investigators determined 12 high-resolution structures of representative mutant AChRs with and without therapeutic compounds. By combining these structural data with functional studies, they identified common mechanisms that explain the two major forms of CMS.
Fast-channel CMS is caused by loss-of-function mutations that reduce receptor opening and weaken neuromuscular transmission. The researchers discovered a previously unknown allosteric binding pocket that can be targeted by positive allosteric modulators (PAMs), compounds that enhance receptor activity without directly activating the channel.
Notably, different PAMs restored receptor function in different patient mutations rather than producing a universal effect. The authors write that this “mutation-specific activity underscores the capability and necessity of tailoring therapies to individual patient genotypes.”
The study also showed that the newly identified drug-binding pocket is largely absent until a PAM binds, creating an opportunity to design more effective compounds that stabilize receptor function. The authors conclude that these findings point to “a new class of allosteric drugs” with potential applications not only in fast-channel CMS but also in disorders such as myasthenia gravis, in which acetylcholine receptor function is compromised.
The team also investigated slow-channel CMS, a gain-of-function disorder in which receptors remain open too long, causing excessive calcium influx and progressive damage at the neuromuscular junction.
Structural analyses revealed that the current therapies quinidine and fluoxetine act through a shared mechanism, blocking the receptor pore despite their distinct chemical structures.
The investigators also evaluated reboxetine, an antidepressant already approved in several countries. Unlike the existing drugs, reboxetine selectively inhibited abnormal receptor activity across multiple slow-channel mutations while largely sparing normal receptor function.
The authors believe that reboxetine’s ability to suppress pathological receptor activity, together with its established clinical safety profile, “positions it as a potential candidate for slow-channel CMS therapy,” although they caution that its known adverse effects warrant careful evaluation in future clinical studies.
Beyond identifying therapeutic opportunities, the study establishes unifying principles of CMS pathogenesis. The researchers found that fast-channel mutations weaken the coupling between acetylcholine binding and channel opening, whereas slow-channel mutations stabilize an abnormally widened, desensitized-like pore. These shared structural mechanisms explain why genetically diverse mutations produce similar clinical symptoms while requiring different therapeutic strategies.
The work also revises understanding of receptor biology. The authors write that their findings “overturn the traditional view of the β subunit as merely a structural scaffold,” instead demonstrating that it plays “a central role in the gating cycle.”
Overall, the researchers conclude that their integrated structural and functional analyses define how CMS mutations disrupt receptor gating, reveal the molecular basis of current and candidate therapies, and identify new druggable sites for intervention. They conclude that the work provides “a roadmap towards the development of safer and more effective, mutation-specific treatments for both fast-channel and slow-channel CMS.”
The post Structural Biology Reveals New Drug Targets for Rare Neuromuscular Disease appeared first on Inside Precision Medicine.
Why Long, Uninterrupted Sitting May Matter for Cancer Prevention
Public health advice has long emphasized exercise: move more, meet weekly activity targets, reduce time spent sitting. But a growing body of evidence suggests that the pattern of inactivity may also matter. Sitting for long, uninterrupted periods may not carry the same health implications as the same amount of sedentary time broken up by movement.
A new study published in PLOS Medicine adds cancer outcomes to that discussion. Researchers analyzed accelerometer data from 91,292 UK Biobank participants who wore wrist activity monitors for seven days and were then followed for a median of more than 12 years. The study found that prolonged sedentary behavior was associated with higher risk of cancer mortality and cancer incidence, while interrupted sedentary behavior showed the opposite pattern.
Beyond “sit less, move more”
Sedentary behavior includes waking activities such as sitting, reclining, or lying down that require very low energy expenditure. Most guidelines and public health messages focus on total sedentary time. That is understandable: total sitting time is easy to communicate and has been repeatedly linked to poor cardiometabolic outcomes.
But the new study asks a more precise question: does it matter whether sedentary time happens in long blocks or is regularly interrupted?
The researchers defined prolonged sedentary behavior as bouts lasting at least 30 minutes in which at least 90% of the time was sedentary. Interrupted sedentary behavior included shorter bouts or sedentary periods broken up by movement. This distinction allowed the team to examine not only how much time people spent inactive, but how that inactivity was distributed throughout the day.
Long, unbroken sedentary bouts linked to higher risk
Each additional hour per day of prolonged sedentary behavior was associated with a 9% higher risk of cancer death. Prolonged sedentary time was also associated with higher overall cancer incidence, obesity-related cancers, and type 2 diabetes-related cancers.
Interrupted sedentary behavior showed an inverse association across the same outcomes. In other words, sedentary time that was broken up by activity was not linked to the same pattern of risk as long, uninterrupted bouts.
The authors summarize the implication clearly: “These findings suggest that not only the total amount of sedentary time, but also how sedentary time is accumulated, may be important for cancer risk.”
This matters because sedentary behavior is widespread and often built into modern work, transport, and leisure routines. For many people, the practical question is not whether they can avoid sitting altogether, but whether they can interrupt long sitting periods often enough to reduce risk.
Light movement should not be ignored
The study also used substitution models to estimate what might happen if sedentary time were replaced with different types of activity. Replacing one hour per day of prolonged sedentary behavior with light physical activity was associated with a 12% lower risk of cancer death. Replacing 30 minutes per day with moderate physical activity was also associated with lower cancer mortality risk.
That finding is important because light activity is more achievable for many people than structured exercise. Standing up, walking slowly, doing household tasks, or taking brief movement breaks may not feel like “exercise,” but they may still interrupt metabolically harmful patterns of prolonged inactivity.
As the authors note, “light movement shouldn’t be ignored.”
The biological rationale is plausible. Experimental studies have shown that breaking up sitting with short activity bouts can improve glucose and insulin responses compared with uninterrupted sitting. Prolonged sedentary time may also contribute to low-grade inflammation, impaired immune function, insulin dysregulation, and ectopic fat accumulation—pathways that have all been discussed in relation to cancer risk.
A public health signal, not proof of causation
The study has important strengths. It used device-measured activity rather than self-reported sitting time, reducing recall bias. It also followed participants for more than a decade and included multiple cancer outcomes.
Still, the findings should be interpreted carefully. This was an observational study, so it cannot prove that prolonged sitting directly causes cancer or cancer death. UK Biobank participants are also known to be healthier and more physically active than the general UK population, which may limit generalizability. Activity was measured over only seven days, and the monitors could not capture the context of sedentary behavior, such as whether someone was sitting at work, watching television, driving, or resting because of underlying illness.
The authors also note that residual confounding cannot be ruled out. People who sit for long uninterrupted periods may differ from others in ways that are difficult to fully measure, including occupation, frailty, health status, or broader lifestyle patterns.
Rethinking cancer prevention in everyday terms
Cancer prevention is often framed around smoking, alcohol, diet, body weight, vaccination, screening, and exercise. Sedentary behavior is increasingly part of that picture, but this study suggests the message may need to become more specific.
The goal may not only be to reduce total sitting time, but to avoid accumulating that time in long, uninterrupted blocks. For public health, that is a potentially actionable target: movement breaks at work, walk-and-talk meetings, standing transitions, household activity, or brief light-intensity movement after long periods of sitting.
The study does not suggest that movement breaks replace established cancer prevention measures. Nor does it mean that every hour of sitting carries the same risk for every person. But it does support a more nuanced view of inactivity: the body may respond differently to sedentary time that is regularly interrupted than to sedentary time accumulated in prolonged bouts.
As activity monitors become more common and prevention science becomes more personalized, cancer prevention advice may eventually move beyond broad exercise targets toward daily behavior patterns. For now, the message is simple enough: long sitting spells may be worth breaking, even with light movement.
The post Why Long, Uninterrupted Sitting May Matter for Cancer Prevention appeared first on Inside Precision Medicine.
Mining Association Rules From a Multimodal Dataset of a Digital Therapeutics Application for Sleep Improvement Through a Healthy Lifestyle: Quantitative Study
Background: The demand for sleep interventions is high and steadily growing. Digital therapeutics (DTx) can help individuals improve their sleep remotely, over an extended period, and with less effort from medical professionals. Obstructive sleep apnea (OSA), one of the most prevalent and consequential sleep disorders, can be treated with health-supporting behavior changes, such as physical exercise and weight loss, and, therefore, acts as a promising application for DTx. Objective: The study aimed to analyze a digital intervention from both medical and technological perspectives by moving beyond clinical markers and exploring more deeply how the DTx application was used. This study aimed to propose a novel way in which association rules can function as an exploratory tool to analyze the sleep, behavior, and engagement of participants with the DTx application on a day-to-day level. Methods: A lifestyle intervention study (N=192) targeted at adults with mild-to-moderate OSA aimed to reduce their OSA severity using a DTx application and an exercise program over a study period of 12 weeks. The participants’ OSA severity was assessed through polysomnography at the beginning and at the end of the study period, and the participants tracked their sleep with a digital sleep diary and a smartwatch over the course of the entire study. The DTx application provided data on when and how the participants pursued the proposed lifestyle interventions. These heterogeneous data sources were combined into one multimodal dataset, which was explored through descriptive statistics. Ultimately, the data were turned into a transaction-based format, and association rules were derived using the Apriori algorithm. Results: Analyzing the participants’ interaction with the application revealed the lifestyle interventions they pursued and how their behavior and sleep patterns changed over time. The Apriori algorithm generated a set of association rules with lift and confidence scores that were significantly higher than those for the co-occurrence of items through random chance. The rules show co-occurrence of missions and items from the sleep diary, as well as items derived from the watch measurements. Conclusions: The study showed the richness of the various data sources provided by a digital intervention using wearables and how they can be used to get an in-depth understanding of the study. The generated association rules showed the presence of significant co-occurrences across the different data modalities and highlighted their effectiveness as an exploratory tool for multimodal health data.
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Chimeric Allergen Receptor Treg Cells Suppress Allergic Asthma in Mice
Genetically engineered CAR T cells expressing artificial receptor proteins are increasingly used in the clinic to boost the immune system’s response against leukemias and other cancers. Researchers at Lausanne University Hospital and University of Lausanne, and at Center for Human Immunology Lausanne, have now adapted this approach to suppress the immune system’s response to a common birch pollen allergen. The investigators developed regulatory T cells (Tregs) armed with chimeric allergen receptors (CAlleR Tregs), which in tests reduced or preventing asthma symptoms in mice sensitized to the allergen. The team suggests that their technique could eventually be used to treat a wide variety of allergies in humans.
“Our study provides proof-of-concept and preclinical evidence that CAlleR Tregs redirected against a birch pollen allergen can downmodulate birch pollen–induced allergic asthma,” said study lead Yannick D. Muller, MD, PhD, an associate professor at Lausanne University Hospital and the University of Lausanne.
Muller and colleagues reported on their study in Journal of Experimental Medicine (JEM) in a paper titled “Chimeric allergen receptor regulatory T cells suppress birch pollen allergic airway inflammation,” concluding “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.”
Asthma affects over 300 million people worldwide, around 60% of whom suffer from allergic asthma. Allergens trigger an immune response in a patient’s airways, causing inflammation, excessive mucus production, and difficulty in breathing. “Allergic asthma is driven by an exacerbated type 2 immune response, characterized by the overproduction of IL-4, IL-5, and IL-13 by Th2 cells,” the authors explained. These cytokines trigger events that ultimately result in airway hyperresponsiveness, and airway mucus plugging, which is the primary cause of death in asthma.
Allergen immunotherapy (AIT), which involves the administration of gradually increasing doses of allergen, is the only treatment that addresses the underlying cause of asthma. Yet, it is not recommended for patients with severe asthma, representing the most vulnerable population at greatest risk of asthma-related morbidities and mortality. “This highlights the need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma,” Muller commented.
Regulatory T cells (Tregs) are immune cells that can dampen the body’s immune responses and prevent excessive inflammation. Tregs are being investigated as potential therapies for a variety of inflammatory and autoimmune disorders. “Importantly, Tregs can be expanded ex vivo and reinfused with multiple clinical trials evaluating their potential in autoimmune and inflammatory disorders,” the team continued. “However, Treg therapy has shown only limited efficacy, which has been mostly attributed to the lack of antigen specificity.”
Muller and colleagues wondered whether they could boost the therapeutic potential of Tregs by genetically engineering them to express receptor proteins that recognize specific allergens. This approach is analogous to the CAR T cell method that is now commonly used to treat cancers: cytotoxic T cells are engineered to express chimeric antigen receptors that specifically recognize proteins on the surface of cancer cells, directing the immune system to attack and kill the tumor cells.
A leading cause of allergic asthma is birch tree pollen, to which 8–16% of the European population are sensitive. The birch allergen Bet v1 is the most abundant allergenic protein, the authors commented. And while AIT for birch pollen–associated rhinitis and asthma has been shown to be effective, it is contraindicated for patients with severe and uncontrolled asthma. “This highlights the unmet need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma.”
Muller’s team constructed chimeric allergen receptors (CAlleRs) that specifically recognize the Bev v1 component of birch tree pollen. These CAlleRs were based on antibodies isolated from a birch-allergic patient, linked to protein signaling domains that can activate Treg cells. “We identified and characterized four novel anti–birch-specific antibodies and generated single-chain variable fragments (scFvs) fused to a CD28-ζ signaling domain,” the investigators noted.
Exposure to the birch pollen allergen, when stabilized by noncompetitive antibodies, boosted the suppressive activity of Tregs expressing these CAlleRs. The researchers found that simultaneous binding by a CAlleR and a non-competing antibody promotes receptor–allergen cross-linking underlying a novel mechanism to induce T cell activation by soluble antigens. “This mechanism opens new avenues not only for rewiring synthetic receptors against any soluble antigens including autoantigens for therapeutic intervention but also for delineating a more global pathway for antigen cross-presentation in allergies.”
Muller and colleagues injected these CAlleR-expressing Tregs into mice that were already allergic to birch pollen. When these treated animals were re-exposed to birch pollen, they showed decreased signs of allergic inflammation, reduced mucus production, and increased lung function. Next, the researchers injected CAlleR-expressing Tregs into mice that had never been exposed to birch pollen. When these animals were subsequently exposed to pollen, they failed to develop any asthma symptoms.
The team concluded, “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.” Muller added, “Future studies should evaluate the persistence and stability of CAlleR Tregs over time and define the optimal modalities for implementing such a therapeutic approach.” CAlleRs could also be developed that specifically suppress the immune response to other common allergens, including house dust mites or certain food allergens.” Future work should evaluate whether such approach could also be suitable to restore tolerance against food allergies,” the investigators said.
The post Chimeric Allergen Receptor Treg Cells Suppress Allergic Asthma in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.
STAT+: Online GLP-1 prescriptions are often fast, easy — and low on clinical oversight
A secret shopper study has pulled back the veil on the practices of nearly 50 telehealth sites that prescribe popular GLP-1 medications for weight loss.
Direct-to-consumer telehealth companies have grown rapidly in response to patients’ demand for GLP-1s like semaglutide and tirzepatide, especially after shortages created a market for compounded versions that aren’t approved by the Food and Drug Administration. As online prescribing has grown, clinicians and public health experts have raised concerns about the potential for lax virtual care practices to put patients at risk.
In a study published Monday in the Journal of the American Medical Association, one researcher at Yale University set out to document those online prescriptions by posing as a patient. The results capture what many Americans have learned in the last few years: It is extraordinarily fast and easy to get a GLP-1 online.
ALS Drug Extends Survival in Mice, Targets TDP-43 Low-Complexity Domain
In a new study published in Nature Aging titled, “Therapeutic targeting of the conserved region within the low-complexity domain of TDP-43 is neuroprotective and extends survival in amyotrophic lateral sclerosis mice,” researchers from University of Arizona present a new therapeutic target to shield nerve cells from the damage of ALS.
“Current FDA-approved treatments for ALS provide only modest benefits. There is an urgent need for a real breakthrough,” said Xinglong Wang, PhD, corresponding author of the study a professor at the R. Ken Coit College of Pharmacy.
ALS is difficult to treat because diagnosis occurs after substantial nerve cell damage. Causes of ALS are unclear. Fewer than one in 10 cases are inherited through a known genetic mutation. More than 90% of cases arise sporadically with no family history or clear genetic cause. However, nearly all cases demonstrate abnormal TDP-43 aggregation inside nerve cells, which often informs post-mortem diagnosis.
“We asked a simple question that had never been tested: is there one specific part of TDP-43 that’s causing the harm, something a drug could switch off without disturbing the rest?” Wang said.
The team found a region of TDP-43 were disease-causing mutations clustered. When this region was deleted in mice, the nerve cell death caused by TDP-43 dropped sharply while normal protein function remained intact. The researchers identified experimental drug, XL20, which could latch onto the target region in the TDP-43 protein. Notably, the drug could cross the blood-brain barrier.
In mice, the XL20 extended median survival by approximately a week, protected nerve cells and reduced muscle weakness. When XL20 was tested on human motor neurons, the specialized nerve cells in the brain and spinal cord, the experimental drug reversed damage.
Wang says XL20 represents a promising candidate for future clinical development. As ALS typically develops over months to years after symptoms first appear, earlier treatment could provide greater opportunity to slow disease progression.
Additionally, the study’s findings may have applications for other neurological diseases. The same TDP-43 pathology is central to limbic-predominant age-related TDP-43 encephalopathy (LATE), a common dementia which affects roughly one in three people over 80. TDP-43 pathology is also found in more than half of Alzheimer’s patients and is associated with faster cognitive decline.
“The same TDP-43 pathology is implicated in several other neurodegenerative diseases,” Wang said. “If future studies show this approach works in those diseases as well, it could eventually benefit a much larger patient population.”
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Augmented reality-based fine arts education experiences and adolescents’ perceived reduction in depressive symptoms: a self-report study of associations with psychological resilience, rumination, and emotional regulation
As depressive symptoms among adolescents continue to rise, increasing attention has been directed toward educational contexts that may support psychological well-being. Augmented reality, characterized by immersive, interactive, and multisensory affordances, has been increasingly incorporated into fine arts education. However, it remains insufficiently understood how adolescents’ perceived AR-based fine arts education experiences are associated with psychological resilience, emotional regulation, perceived reduction in rumination, and perceived reduction in depressive symptoms. Using post-course self-report questionnaire data from 518 Chinese adolescents, this study tested a cross-sectional associational model with structural equation modeling, without making causal or clinical claims. The empirical results indicate that adolescents’ perceived AR-based fine arts education experiences were positively associated with self-reported perceived reduction in depressive symptoms. Additionally, these experiences were positively associated with self-reported psychological resilience and perceived reduction in rumination. Self-reported psychological resilience and perceived reduction in rumination were positively associated with self-reported emotional regulation, and this regulation was positively associated with self-reported perceived reduction in depressive symptoms. These findings support a correlational psychological model linking perceived AR-based fine arts education experiences with adolescents’ self-reported psychological perceptions and perceived reduction in depressive symptoms. Theoretically, this study contributes to the literature on arts education, educational technology, and adolescent mental health. Practically, the findings suggest that immersive art-learning environments may be perceived by adolescents as supportive contexts for psychological resources. The innovation of this study lies in reframing AR-based fine arts education experiences as psychologically meaningful educational experiences associated with adolescents’ self-reported psychological perceptions
Neurophysiological effects of transcranial alternating current stimulation combined with multidisciplinary rehabilitation in Parkinson’s disease
IntroductionMotor impairment in Parkinson’s disease (PD) often becomes inadequately controlled as the disease progresses. Rehabilitation therapy combined with noninvasive neuromodulation has shown benefits, yet the neural mechanisms underlying this remain unclear. This study aimed to identify neurophysiological and brain network features associated with motor improvement following high-intensity transcranial alternating current stimulation (Hi-tACS) combined with multidisciplinary intensive rehabilitation therapy (MIRT).MethodsThis secondary analysis was based on a randomized controlled trial (ChiCTR2300071969). Thirty patients receiving Hi-tACS combined with MIRT were included. Responders were defined as patients achieving a minimal clinically important difference improvement greater than 3.25 points on the Unified Parkinson’s Disease Rating Scale part III. Electroencephalographic spectral analysis, resting-state functional connectivity, and dynamic brain states assessed using hidden Markov modeling were performed. Partial correlation analyses were conducted for group-differentiating measures, controlling for age and disease duration.ResultsCompared with non-responders, responders showed increased temporal high beta frequencies relative power (95%CI 0.85(0.01–1.66), P = 0.047), reduced connectivity between the default mode and sensorimotor networks (95%CI -0.89(-1.71–0.05), P = 0.038), and decreased fractional occupancy of state 3 (95%CI 0.03(0.00–0.28), P = 0.033) and 6 (95%CI 0.02(0.00–0.35), P = 0.038). After Bonferroni correction, only changes in temporal high beta frequencies relative power were negatively correlated with changes in total UPDRS part III scores (R = -0.59, PBON = 0.012) and rigidity subscores (R = -0.74, PBON < 0.001).DiscussionThese results suggest that motor improvement following combined Hi-tACS and MIRT in PD patients is associated with alterations in brain oscillations and network connectivity, particularly in high-beta frequencies. The findings contribute to understanding the neural mechanisms underlying rehabilitation and neuromodulation in PD. Future studies should investigate the long-term effects of this intervention and its applicability in larger, more diverse populations. Moreover, exploring additional biomarkers may help identify individuals who are most likely to respond to this treatment.Clinical Trial Registrationhttps://www.chictr.org.cn, identifer ChiCTR2300071969.