Background: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. Objective: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. Methods: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. Results: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. Conclusions: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. Trial Registration: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349

Background: Chronic low back pain (CLBP) is a common public health problem. Progressive loss of muscle strength leads to long-term chronic pain and disability. Yijinjing exercises, an ancient therapy dating back thousands of years, are widely used in China to treat low back pain. However, little is known about its benefits and scientific evidence for back extensor strength. This trial aimed to assess the efficacy of Yijinjing on disability and dorsal extensor strength in patients with CLBP. Objective: We present a randomized controlled study to evaluate the efficacy of the traditional Chinese exercise Yijinjing on disability and back extensor strength in patients with CLBP. Methods: This is a 2-arm, parallel-design, assessor-blinded, and analyst-blinded randomized controlled trial. The 106 participants with CLBP who were recruited will first receive basic traditional Chinese manual therapy to help relieve their physical discomfort. Second, they will be randomly divided into a Yijinjing group (n=53) and a control group with functional exercises (n=53) at a ratio of 1:1. The interventions for both groups will be carried out twice a week for 4 weeks. Patients in both groups will be followed up at 1 and 3 months after the intervention. The primary outcome is disability (measured by the Oswestry Disability Index). The secondary outcomes included pain intensity (assessed by the Numerical Rating Scale), data from isokinetic dynamometry, flexibility (assessed by the fingertip-to-floor test), mood (evaluated by the Pain Catastrophizing Scale and Fear Avoidance Beliefs Questionnaire), and quality of life (measured by the EQ-5D-5L). All adverse effects will be assessed using the Treatment Emerging Symptoms Scale, and data will be analyzed using an intention-to-treat analysis. Results: The trial was funded in December 2023. The Institutional Ethics Committee of Yueyang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, approved this study. The first patient was enrolled in February 2024, and as of August 2024, a total of 106 participants have been recruited. Data analysis has not yet begun and is expected to be published in January 2025. The protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR2400081105). Conclusions: If this trial proves effective, it will guide the setup of a randomized controlled trial to demonstrate whether traditional Chinese exercise Yijinjing improves disability in patients with CLBP and is more effective than usual stretching exercises. Clinical Trial: Chinese Clinical Trial Registry ChiCTR2400081105; https://www.chictr.org.cn/showprojEN.html?proj=214425

Background: Depression and anxiety are among the most common mental health concerns globally. Efficacious treatments such as cognitive behavioral therapy exist but remain difficult to access and scale. Cognitive behavioral immersion (CBI)—a cognitive behavioral skills training intervention delivered by peer coaches in the metaverse—has been developed to address these barriers. CBI can be used through a virtual reality headset or via flat-screen devices such as phones, tablets, or computers. Pilot data have established its usability among participants with clinical levels of depression and anxiety. However, more research is needed to determine whether CBI causes decreases in these symptoms and how delivery via virtual reality compares to flat-screen devices. Objective: This protocol aims to conduct a randomized controlled trial evaluating the efficacy of immersive CBI accessed via a virtual reality headset (CBI-VR) as compared to a less immersive (but more accessible) CBI condition accessed via a flat-screen device (CBI-FS) and each to a delayed access control (DAC). Methods: A total of 306 adults experiencing clinical levels of depressive symptoms are being recruited nationally to participate in this web-based trial. Participants will be randomized according to a 1:1:1 ratio to one of three conditions: (1) CBI-VR, (2) CBI-FS, and (3) DAC. The CBI program consists of eight weekly 60-minute group sessions led by trained peer coaches who teach cognitive behavioral skills. The acute period of each condition will last 8 weeks with a follow-up period of 6 months. The primary outcome is depressive symptoms; secondary outcomes are anxiety symptoms and quality of life. Outcomes will be assessed once at baseline, weekly during the course of the intervention, and monthly during follow-ups. We will use hierarchical linear models to assess differences in the rate of symptom change among conditions. We will also explore potential prognostic (demographics and immersion) and prescriptive (cognitive behavioral skills, group alliance, and program engagement) predictors, as well as potential mechanisms (cognitive change and social support) of response. Results: We hypothesize that participants randomized to either CBI group will experience greater symptom improvement than those in DAC and that CBI-VR participants will improve more than CBI-FS participants. This study was funded in September 2023. Data collection began in February 2024. As of January 2025, all 306 participants have been enrolled. Data collection should conclude by September 2025. Data have not yet been analyzed. Expected results to be submitted for publication in the winter of 2025. Conclusions: This trial will determine if CBI via either device is efficacious as compared to DAC and whether virtual reality enhances outcomes. Findings will contribute to the literature on using the metaverse and virtual reality to facilitate effective accessible mental health interventions, particularly for depression. Trial Registration: ClinicalTrials.gov NCT06418997; https://clinicaltrials.gov/study/NCT06418997

Background: Evidence suggests that the communication of type 2 diabetes (T2D) genetic risk alone has limited effectiveness on facilitating behavioral changes among individuals of European descent. Although the use of wearable devices has been associated with changes in behavior, the effects of combining personalized precision medicine with wearable devices on behaviors related to T2D prevention remain unclear. This study aims to assess the novel effects of T2D genetic risk communication and wearable device functions on objectively measured moderate to vigorous physical activity (MVPA) time among East Asian individuals with overweight or obesity.

INTRODUCTION: Different biologically active products have been applied to manage pain and mandibular functional disability in intra-articular Temporomandibular Joint Disorders (TMD) but without effectively controlling the degenerative joint disease. Platelet concentrates aim to enhance tissue healing and facilitate its regeneration. Intra-articular injections of liquid Platelet-Rich Fibrin (PRF) in patients with TMD have demonstrated effectiveness in the management of pain and dysfunction, also having a stimulatory effect on cartilage and bone tissuOeBs.JECTIVE: This review aims to examine how research has been conducted regarding the use of PRF as a treatment tool for Temporomandibular Joint Disorders (TMD). INCLUSION CRITERIA: This review will focus on studies that address adults with TMD without restrictions on gender or ethnicity. TMD will be classified according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) physical axis (Axis I). Also, we will include publications in any language or date of publication. METHODS: This protocol will follow the JBI guidance for Scoping Reviews. We shall conduct a literature search to identify published research, with no limits on the year of publication/conception, format, or language. Two independent reviewers will screen and select publications based on inclusion criteria. The review decision process will be provided in a flowchart-based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations for Scoping Reviews. Finally, we shall present extracted data from each study in piloted forms in conceptual categories such as intervention type, population and sample size, duration of intervention, aims, the methodology adopted, key findings, and gaps in the research.

Background: From birth, many young Pacific people in Aotearoa New Zealand experience a disproportionately high burden of psychological distress, metabolic disease, and socioeconomic disparities within education and employment which contribute to significant health inequalities. Further research is needed to understand the drivers influencing these outcomes.

Background: The gut microbiota is attracting increasing interest as a factor possibly impacting colorectal cancer risk, therapy toxicity, and, as a consequence, patient’s quality of life. It has been observed that microbial imbalance in the gut and in cancer tissue is facilitated by a Western type of diet, rich in meat, sugars, and refined grains, while a Mediterranean diet, rich in low saturated fat and fibers, promotes gut eubiosis, and results in reduced risk of developing colorectal cancer. Specifically, a high fiber content diet has been associated with a reduced incidence of therapy related adverse events in patients with malignant melanoma.

Background: Human-machine interaction (HMI) has gained significant attention in the context of advanced production technologies, especially concerning trust and acceptance. However, the investigation of the subjective well-being of operators working with these technologies in manufacturing companies has been largely overlooked. Moreover, previous research mostly relied on a single data-collection method, either quantitative or qualitative, thereby failing to capture a rich picture of their cognitive and affective states. Objective: This cross-sectional study protocol aimed to fill that gap by examining operators’ subjective well-being and workplace dynamics, including fluency in HMI, negative attitudes toward technologies, and social relationships among coworkers in manufacturing companies. Methods: We adopt a mixed methods approach, incorporating both quantitative and qualitative data collection techniques. Quantitative data will be gathered via a digital survey containing self-report questionnaires. A path analysis will be performed to explore the multiple mediating roles of fluency in HMI and negative attitudes toward such technologies between cognitive and affective well-being. We further qualitatively investigate the operators’ lived experience in HMI using semistructured audio-recorded interviews. A thematic analysis relying on text-mining techniques will then be conducted to explore operators’ textual data. Results: We quantitatively expect that fluency in HMI may act as a protective factor for operators’ affective well-being, while negative attitudes toward advanced production technologies may contribute to the development or worsening of operators’ psychological distress. From a qualitative perspective, we intend to seamlessly merge quantitative insights to create a more comprehensive and well-grounded analysis. Moreover, the integrated interpretation of both the quantitative and qualitative data collected will generate a consensus report, which will aim to serve as a practical framework for guiding workplace policies and training programs meant to foster subjective well-being and effective HMI. At the time of publication, we have collected data from 12 participants and scheduled a further data collection session. Conclusions: Embracing one of the fundamental pillars of Industry 5.0, human-centricity, by detecting potential psychological issues early, organizations can create a workplace that prioritizes the well-being of operators. Early recognition and prevention are crucial to promoting operators’ mental well-being involved in HMI.

Background: Knowledge of the burden of disease at the national level is crucial for understanding regional health patterns and epidemiological trends. Regular updates and methodological enhancements are essential to produce accurate estimates that effectively represent the current health landscape, thereby assisting policymakers in resource allocation and strategic planning. Objective: The objective of this study protocol is to revise the list of diseases and injuries; estimate years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) in phase 1; and identify the list of risk factors and determine risk-attributable burdens in phase 2. Methods: The Malaysian Burden of Disease (MBOD) Study adopts the Global Burden of Disease Study approach, using various metrics to quantify health loss related to specific diseases, injuries, and risk factors. These metrics include deaths, YLLs, YLDs, and DALYs, which are calculated in terms of counts, age-specific rates, and all-age rates. In addition, this MBOD Study calculates risk-attributable deaths, YLLs, YLDs, and DALYs for all relevant risk factors. This study also conducts focus group discussions to develop the lists of diseases and injuries as well as risk factors. Results: By December 2024, we had successfully completed the focus group discussions, which led to the development of an updated and comprehensive list of diseases and injuries. Furthermore, mortality data collection is complete, and the calculation of YLLs is currently in progress. The YLD calculation is expected to conclude by the end of 2025. While phase 1 is underway, phase 2, which addresses risk factor estimation, is scheduled for completion in mid-2026. Conclusions: This MBOD Study offers a comprehensive and current framework for assessing the burden of disease in Malaysia, with continuous improvement initiatives to enhance the list of diseases and injuries and refine the methodology for more accurate estimation and risk factor analysis.

Background: In recent years, the rapid emergence and global spread of dengue has become a public health burden. Clinical surveillance alone has limited capacity, with delayed detection of upcoming outbreaks. Hence, the potential use of wastewaterbased surveillance (WBS) for early detection of incoming surges of dengue cases could complement proactive public health action. However, there are still substantial gaps in the standard approach for sampling and detection methods in dengue WBS. Objective: This review aims to determine the current methodological approach for the detection of dengue virus (DENV) in wastewater across geographical areas. Methods: The review will be conducted systematically following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the initial stage, peer-reviewed publications from PubMed, Embase, Scopus, and Web of Science will be searched using predefined terms such as “Dengue” and “WBS.” Keywords will be adjusted to suit each database to identify studies related to DENV WBS from inception until June 2025. Subsequently, the references from relevant articles will be screened for eligibility. All data will be extracted from full-text articles highlighting the characteristics and methodological context of the investigated DENV WBS using a standardized form. The ROBINS-I (Risk of Bias in Non-randomized Studies - of Interventions) tool and the GRADE (Grading of Recommendations Assessment, Development, and Evaluations) system will be used to assess study bias and the quality of the evidence. Further descriptive analysis and meta-analysis will be applied to evaluate the methodologies for DENV WBS. Results: The data on DENV detection in wastewater will be synthesized by analyzing sampling techniques, viral detection method, study sites, geographic locations and dengue serotype. A meta-analysis will be conducted using a random-effects model if data are heterogeneous, with pooled estimates reported as 95% CIs. Heterogeneity will be assessed using I² and chi-square tests, with subgroup and sensitivity analyses conducted as needed. Findings will be reported in accordance with PRISMA 2020. As of October 2025, records have been identified from the databases and data analysis is expected to be completed by the first quarter of 2026. Conclusions: This protocol outlines a systematic approach to identifying and evaluating existing methods for detecting DENV in wastewater. This research aims to provide valuable insights into best practices for dengue surveillance and offer guidance for future research by highlighting current strengths and limitations in the field.

Background: Surgical resection is the primary curative treatment for early-stage lung cancer—the leading global cause of cancer mortality, responsible for nearly 1 in 5 cancer deaths in 2022. Obesity is a global health concern that may influence surgical outcomes; yet, its impact on perioperative outcomes following lung cancer surgery remains controversial. Objective: This protocol outlines a meta-analysis and systematic review to evaluate the association between obesity and perioperative outcomes in patients who underwent a lung cancer resection. Methods: Observational studies related to patients with lung cancer who underwent surgical resection were searched in 5 English and 3 Chinese literature databases: PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, Chinese National Knowledge Infrastructure, Wanfang, and the Chinese Biomedical Database. The search period for these 8 electronic databases was from inception to 2025. The PROSPERO database and the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) database were also searched. Qualified studies were screened and selected by 2 authors independently. The literature obtained were imported into NoteExpress to screen the titles and abstracts. After reading the full text of the remaining studies, the final number of studies were determined. Two reviewers independently extracted data from the included studies by using a predesigned data extraction tool. The Newcastle-Ottawa Scale was used to evaluate the quality of the research. The primary outcome of this study was to evaluate the postoperative mortality in people living with obesity undergoing lung cancer surgical procedures. The secondary outcomes were the postoperative complications, average length of stay, blood loss during the operation, and operation time in people living with obesity undergoing lung cancer surgical procedures. For dichotomous data, we plan to present results as risk ratios with 95% CIs. For continuous data, we will use mean difference with 95% CIs. The Review Manager software (version 5.4) will be used for the meta-analysis and statistical analysis. Sensitivity analysis and Egger test will be performed with Stata software (version 16.0). Results: The results are not yet accessible because this is a protocol for a systematic review and meta-analysis. The protocol is registered in PROSPERO under the registration number CRD42025648330. By August 26, 2025, we completed the literature search of the 8 databases and completed the selection and extraction of data. Conclusions: This study will synthesize existing evidence to clarify whether obesity is a risk factor for adverse outcomes or if it confers a protective effect, as suggested by the obesity paradox. These findings will guide clinical decision-making and improve perioperative care for obese people with lung cancer. Trial Registration: PROSPERO CRD42025648330; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025648330

Background: Urban Indigenous populations face disproportionate mental health challenges, including high rates of posttraumatic stress disorder, depression, and substance use disorders, yet they have limited access to health services, especially culturally relevant care. The mechanism for providing care to Indigenous people in the United States, the Indian Health Service, is significantly underfunded and only accessible to certain Indigenous people. With more than 70% of Indigenous individuals in the United States living in urban settings, there is a growing need for innovative health care solutions. A community-based, Indigenous-led health and mental health–focused nonprofit in the northeast United States developed ShockTalk, a tele–mental health linkage-to-care app tailored specifically for Indigenous communities, to fill this gap. Objective: This study aims to assess (1) the feasibility, including accessibility, experience, and value, of ShockTalk for practitioners and clients interested in providing or receiving culturally responsive mental health treatment, and (2) changes in client attitudes related to tele–mental health treatment value and trust in ShockTalk technology. Methods: This study outlines the development and pilot study of ShockTalk. The conceptual framework is based on the behavioral model of health care use. ShockTalk uses artificial intelligence to connect clients with Indigenous or culturally aligned therapists and facilitates access to care via Facebook Messenger. Using a prewaitlist or postwaitlist design, 5 client participants will be admitted to the study at first, and 5 additional participants at 3 months. Data collection includes presurveys and postsurveys on client attitudes toward mental health treatment and trust in the ShockTalk platform at baseline and a 3-month follow-up, followed by in-depth qualitative interviews at 3 months. A preliminary economic evaluation will track direct costs (ie, therapist time, platform fees, and administrative expenses) and compare relative costs across treatment doses. Analyses will assess the feasibility of data collection and inform a future full-scale trial. Results: This study was funded in April 2022. Data collection occurred between May 2022 and October 2024. In total, 4 client participants and 2 therapist participants were enrolled. Data analysis is complete and results are expected to be published in February 2026. Conclusions: This pilot study will offer insights into optimizing technology-based, culturally relevant mental health care. By examining varying levels of engagement and associated costs, this research seeks to identify the most effective and cost-efficient strategies for improving mental health outcomes in urban Indigenous populations in the United States. ShockTalk has the potential to shape future health care innovations in this field. Findings are expected to contribute significantly to Indigenous mental health care by offering insights into sustainable, accessible, and culturally appropriate telehealth interventions, guiding future policy and practice.

Background: Alcohol use among young adults with HIV is disproportionately high compared to other age groups with HIV, despite its negative health-related consequences. However, alcohol use interventions tailored to the interests and needs of young adults with HIV are scarce. Self-management interventions that include self-monitoring components have the potential to improve chronic illness outcomes and mitigate alcohol misuse. Although wearable technologies promote self-monitoring behaviors and facilitate the delivery of personalized feedback, people rarely adhere to the long-term use of wearables. Objective: The primary aim of this pilot study is to test the feasibility and acceptability of translating theoretically grounded reciprocity and personalized feedback strategies. These strategies will be delivered through app-based messages to promote engagement in wearing a wrist-worn alcohol biosensor among young adults with HIV. Methods: A total of 40 young adults with HIV (aged 18-29 years) will be enrolled in a 30-day pilot microrandomized trial (MRT). The MRT is an experimental design that facilitates the development and optimization of mobile health just-in-time adaptive interventions. Participants will wear the BACtrack Skyn biosensor, a wrist-worn transdermal alcohol biosensor, and play a smartphone-based game geared toward earning points to care for virtual animals. Longer alcohol biosensor wear time will translate into earning more game points. Every morning and evening, participants will be randomized at equal probability to receive (1) a reciprocity message offering a no-strings-attached gift of either 100 game points or US $1, (2) a message with personalized feedback about their Skyn biosensor wear time, or (3) no message. Results: Data collected during this 30-day MRT will be used to examine the feasibility and acceptability of translating theoretically grounded strategies into messages suitable for a mobile health alcohol intervention tailored to young adults with HIV. Recruitment for this study began in spring 2024, with data collection wrapping up in spring 2025. Conclusions: This pilot MRT will provide valuable feasibility and acceptability data and set the stage for a full-scale MRT to optimize the integration of reciprocity and personalized feedback into a just-in-time adaptive intervention that increases engagement in biosensor-based alcohol self-management among young adults with HIV. Trial Registration: Clinicaltrials.gov NCT05431855; https://clinicaltrials.gov/study/NCT05431855

Background: Primary insomnia (PI), commonly identified by difficulties in initiating and/or maintaining sleep, negatively impacts both physical and mental health and increases the risk of occupational and vehicular accidents. Previous researches have indicated that shallow needling, a form of acupuncture, may ameliorate symptoms of primary insomnia. Nevertheless, the scientific evidence regarding its efficacy in enhancing sleep quality remains limited. Objective: This trial aims to assess the therapeutic efficacy of shallow needling in the treatment of chronic primary insomnia in adults. Methods: A single-center, prospective, assessor-blinded, and randomized controlled clinical trial with two parallel arms will be conducted in the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine. A total of 124 participants with primary insomnia will be randomly divided into control group and treatment group in a ratio of 1:1 (n = 62 for each group). The control group will take eszopiclone orally at 1 mg once a day for 4 weeks. In addition to taking eszopiclone, the treatment group will receive shallow needling therapy once daily, five times a week, for 4 weeks. Data will be collected at three timeslots (pre, post, 4-weeks follow-up) and analyzed using SPSS 23.0. The primary outcome measure is Pittsburgh Sleep Quality Index (PSQI), Secondary outcome measures are Hamilton anxiety scale (HAMA), Insomnia Severity Index (ISI), Serum neurotransmitter detection (including the content of dopamine [DA], norepinephrine [NE], and melatonin [MT]), sleep parameters, and Magnetic Resonance Spectroscopy (MRS) of the thalamus. Results: This study has received formal ethical approval (Approval No: IRB 2023-014-02), the first participant was enrolled in August 2023, marking the official commencement of the trial. Participant recruitment for this study is currently in progress. Following the completion of recruitment, data processing and statistical analysis will be initiated. The final results of the study are expected to be prepared and submitted for publication in January 2026. Conclusions: This study will evaluate the therapeutic effectiveness and safety of shallow needling in the treatment of chronic insomnia, so as to provide the necessary scientific basis for the clinical application and promotion of shallow needling. The findings of this study may provide a scientific and standardized treatment protocol for shallow needling in adults with chronic insomnia. Clinical Trial: International Traditional Medicine Clinical Trial Registry ITMCTR2024000409; https://itmctr.ccebtcm.org.cn

Background: Lower limb amputation rates are increasing owing to aging and vascular diseases. However, no standardized rehabilitation protocol has been established for regaining walking ability. Conventional rehabilitation delays prosthetic gait training until 6-8 weeks post amputation, prolonging recovery and increasing medical expenses. Objective: This study aims to evaluate the impact of neurorehabilitation using the Hybrid Assistive Limb (HAL) for Medical Use Lower Limb Type, developed by Japan's Tsukuba University and the robotics company Cyberdyne, on gait acquisition, improvement in activities of daily living (ADL), and enhancement of quality of life (QOL) in patients with lower limb amputation, and assess the effectiveness of early HAL-assisted gait training before and after amputation. Methods: This single-arm trial will include 20 patients undergoing unilateral transfemoral or transtibial amputations. HAL-assisted gait training will be performed 5 days per week (30 minutes per session) until postoperative week 8. The primary outcome is a 2-minute walking distance, while secondary outcomes include muscle strength, balance, gait parameters, and ADL/QOL measures. Statistical analyses will be conducted using SPSS (IBM Corp), and results obtained at the following time points will be compared: preoperative, postintervention, and 6-month follow-up. Results: The planned sample size is 20 patients, calculated using JMP version 12 (SAS Institute) based on an expected 1.5-fold improvement in 6-minute walk distance (effect size 0.8, α=.05, power=0.8). Analyses will be performed using SPSS version 15.0 (IBM Corp). The 2-minute walk test (primary outcome) and secondary outcomes will be compared at baseline, post intervention, and 6-month follow-up using 1-way analysis of variance or Kruskal-Wallis test, and P values <.05 and 95% CIs will be reported. Conclusions: This is the first study to apply HAL-assisted neurorehabilitation to patients with lower limb amputations. Early gait training may increase prosthetic gait acquisition rates, shorten rehabilitation and hospitalization periods, and reduce medical costs. If effective, this study may contribute to the development of a Japan-originated rehabilitation program and provide clinical evidence supporting broader HAL implementation for patients with lower limb amputations. Clinical Trial: Japan Registry of Clinical Trials jRCTs062200031; https://jrct.mhlw.go.jp/latest-detail/jRCTs062200031

Background: Self-reported dietary intake data are crucial in nutrition and health research; however, their accuracy is compromised by challenges such as portion size estimations, food identification, memory-related bias, social desirability bias, and reactivity bias. Dietary assessment in adolescents is particularly challenging due to irregular eating habits, meal skipping, and parent or peer influences, potentially resulting in misreporting. Leveraging adolescents’ receptiveness to technology, we investigated the use of an innovative smartphone app (Traqq) that facilitates dietary assessment using repeated short recalls instead of traditional 24-hour recalls. Evaluation studies of the Traqq app in Dutch adults have shown successful results, but its suitability for other target populations, such as adolescents, requires further investigation. Objective: We designed a comprehensive, 3-phase study to evaluate the Traqq app’s accuracy using repeated short recalls, usability, and user perspectives among Dutch adolescents aged 12 to 18 years. This manuscript details the study setup, research methods, and basic characteristics in phases 1 and 2. Methods: In phase 1, adolescents (aged 12-18 years) downloaded the Traqq app and completed a demographic questionnaire. It was used on 4 random school days over 4 weeks, using 2-hour recalls on 2 days and 4-hour recalls on 2 days. A food frequency questionnaire and 2 interviewer-administered 24-hour recalls served as dietary reference methods to assess the Traqq app’s accuracy. In addition, usability was evaluated using the System Usability Scale and an experience questionnaire. In phase 2, user experiences were further explored through semistructured interviews within a subsample of 24 adolescents. These first 2 phases of this mixed methods study are now finalized for data collection. Phase 3 will focus on collecting user insights to inform app customization through cocreation sessions. Results: Recruitment concluded in September 2022 with 102 adolescents; 98 (96%) provided dietary data via the Traqq app, and 79 (78%) completed the evaluation questionnaire. Adolescents had a mean age of 15 (SD 2) years. The mean BMI was 19.9 (SD 3) kg/m2. A total of 64 (63%) participants were girls, 81 (84%) attended high school, and 88 (92%) were born in the Netherlands. Interviews were held with 6 (25%) boys and 18 (75%) girls. Cocreation sessions will be planned after all data have been analyzed. Conclusions: In this holistic study, we combine quantitative and qualitative methods to evaluate the dietary assessment performance among adolescents of the Traqq app, which was initially designed for adults. Specifically, next to quantitative comparisons of the Traqq app’s dietary assessment methods, we conducted semistructured interviews, and we will carry out cocreation sessions. With this user-centered, synergistic approach, we aim to establish a list of requirements for a dietary assessment app for adolescents, resulting in more efficient assessments, improved compliance, and enhanced overall accuracy in this population. Clinical Trial: ISRCTN Registry ISRCTN46230386; https://www.isrctn.com/ISRCTN46230386

Background: Transgender, nonbinary, and gender diverse (TGD) young adults face a disproportionately high mental health burden, including 2- to 4-fold increased risk of suicidality and depressive distress compared to their cisgender peers. Family and community support are protective factors that may mitigate these adverse outcomes, representing key targets for mental health interventions. Objective: This randomized controlled trial (RCT) evaluates the effectiveness of TransHealthGUIDE, a novel digital, app-based education and support intervention aimed at reducing past 3-month suicidal ideation and past 2-week depressive distress among TGD young adults. Participants are randomized 1:1 to an immediate intervention arm or a 6-month deferred intervention arm (waitlist control). Methods: From 2021 to 2024, a multidisciplinary team of academic and community partners conducted formative research and codeveloped a digital app containing 33 self-paced modules, communication, and interactive resources. The content is grounded in the Social Ecological Suicide Prevention Model and the Gender Minority Stress and Resilience Framework, designed to enhance family support and community connection for TGD young adults and their families. TGD young adults (ages 18-24 years) and their caregivers are prospectively enrolled and randomized in 10 US states (California, Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York, Oregon, Vermont, and Washington, DC). Participants complete self-reported surveys at baseline, 6 months, and 12 months, assessing sociodemographics, family support, community connection, suicidal ideation, depressive distress, and intervention acceptability. App usage and engagement are tracked via metadata. The target sample size is 500 TGD young adults, with 50% (n=250) identifying as people of color and 125 TGD young adult-caregiver dyads. Results: TGD young adult and caregiver communities, including our community advisory board (CAB), have guided all aspects of the project: study design (eg, waitlist control), survey development (eg, self-reported rather than clinician-administered suicidality measures and inclusion of social justice activism as a form of support), intervention content (eg, text, infographics, interviews with TGD people and caregivers, and simulations), and digital app safety features (eg, a quick-exit button for privacy). Recruitment and study screening began on January 21, 2025. As of May 2, 2025, a total of 149 individuals completed a study screener, with 132 (88.6%) of 149 found eligible. Enrollment visits began on April 23, 2025. As of May 2, 2025, five TGD young adults have been enrolled. Ongoing engagement with the CAB will inform iterative improvements throughout the trial. Conclusions: Scalable, app-based interventions tailored to meet the needs of TGD young people hold promise for population-level mental health impact. This RCT—targeting suicidality and depressive distress via education and support for both TGD young adults and their caregivers—addresses a critical gap in mental health interventions for this underserved population. Trial Registration: ClinicalTrials.gov NCT06177600; https://clinicaltrials.gov/study/NCT06177600

Background: Substance use is a high-impact biopsychosocial problem in Chile, where 21% of adults have experienced a severe alcohol use episode. In the past year, the prevalence rates were 12.5% for marijuana, 0.8% for cocaine, and 0.4% for cocaine base paste. Cannabis prevalence in Chile is higher than the global (4.2%) and South American (3.58%) averages. Cocaine prevalence in Chile is lower than in South America (1.62%) but higher than the global average (0.42%). No international reports are available for cocaine base paste. Mental health and substance use programs in Chilean primary care involve psychologists and social workers. Solution-focused brief interventions (SFBIs) are based on solution-focused brief therapy, a strengths-based and person-centered approach in which practitioners adopt a stance of “not being the expert,” respecting clients’ needs and perspectives. Objective: This study aims to determine whether the SFBI implemented by psychosocial teams (psychologists and social workers) for individuals with alcohol and other drug use in primary health care centers leads to better outcomes than usual care. Methods: We will conduct a randomized controlled clinical trial (ClinicalTrials.gov registration pending) comparing a 3-session SFBI (experimental group) with a single session of brief counselling as usual care (control group) in primary care. Interventions will be delivered in person by a psychologist or social worker. A total of 320 participants are expected to be recruited during preventive routine checkups using the Alcohol, Smoking, and Substance Involvement Screening Test. Participants reporting intermediate- to high-risk substance use on this screening tool will be randomly assigned to each group. Research assistants will administer instruments at baseline and at 3-, 6-, and 9-month follow-ups and will be blinded to the assigned treatments. The primary outcome assessed will be substance use patterns, while secondary outcomes include background information, depressive symptoms, anxiety symptoms, and motivation for treatment. Statistical analyses, including t tests, ANOVA, and Fisher exact tests will be conducted depending on variable type and normality. A qualitative component to assess acceptability and pertinence will include focus groups with participants and practitioners, followed by a content analysis. Results: Funding for this study started in April 2024. As of the submission date of this protocol, 55 practitioners from 9 primary health care centers have been trained in SFBIs. Recruitment began in February 2025, with 73 participants enrolled and 23 who dropped out. Recruitment will continue until December 2026. No analyses have been conducted to date. Findings are expected to be published during the second half of 2028. Conclusions: This study strengthens primary care by integrating targeted psychosocial interventions for substance use into existing programs, thereby enhancing real-world applicability. If effective, the intervention could be adopted into routine care and inform public policy on mental health and substance use. Trial Registration:

Background: Information and communication technology (ICT) has made remarkable progress in recent years and is being increasingly applied to medical research. This technology has the potential to facilitate the active involvement of research participants. Digital platforms that enable participants to be involved in the research process are called participant-centric initiatives (PCIs). Several PCIs have been reported in the literature, but no scoping reviews have been carried out. Moreover, detailed methods and features to aid in developing a clear definition of PCIs have not been sufficiently elucidated to date. Objective: The objective of this scoping review is to describe the recent trends in, and features of, PCIs across the United States, the United Kingdom, and Japan. Methods: We applied a methodology suggested by Levac et al to conduct this scoping review. We searched electronic databases—MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase (Excerpta Medica Database), CINAHL (Cumulative Index of Nursing and Allied Health Literature), PsycINFO, and Ichushi-Web—and sources of grey literature, as well as internet search engines—Google and Bing. We hand-searched through key journals and reference lists of the relevant articles. Medical research using ICT was eligible for inclusion if there was a description of the active involvement of the participants. Results: Ultimately, 21 PCIs were identified that have implemented practical methods and modes of various communication activities, such as patient forums and use of social media, in the field of medical research. Various methods of decision making that enable participants to become involved in setting the agenda were also evident. Conclusions: This scoping review is the first study to analyze the detailed features of PCIs and how they are being implemented. By clarifying the modes and methods of various forms of communication and decision making with patients, this review contributes to a better understanding of patient-centric involvement, which can be facilitated by PCIs.

The question of whether and, if so, how creativity and unethical behavior such as dishonesty are related to each other has been addressed in multiple studies, with mixed results overall. The aim of this Registered Report is to shed further light on this issue. We first present a meta-analysis on the relation between creativity and dishonesty comprising the samples from a pre-registered multi-lab study (on a different topic), which indicated no relation between the constructs in question (k = 19, N = 2,154, rp = .02). Next, we examined the relation between creativity and dishonesty in a study (N = 1,152), in which we addressed several limitations of previous research. Specifically, we examined relations between comprehensively assessed creativity and dishonesty using subjective and objective indicators for both constructs. We found mixed results concerning the relation between creativity and dishonesty. In the majority of the confirmatory statistical tests, subjective creativity was positively related, whereas objective creativity was negatively related to dishonesty in the mind game. However, in exploratory analyses, we found that neither subjective nor objective creativity was related to dishonesty in the second dishonesty measure, the sender–receiver game.

A critical step before data-sharing of human neuroimaging is removing facial features to protect individuals’ privacy. However, not only does this process redact identifiable information about individuals, but it also removes non-identifiable information. This introduces undesired variability into downstream analysis and interpretation. This registered report investigated the degree to which the so-called defacing altered the quality assessment of T1-weighted images of the human brain from the openly available “IXI dataset”. The effect of defacing on manual quality assessment was investigated on a single-site subset of the dataset (N = 185). By comparing two linear mixed-effects models, we determined that four trained human raters’ perception of quality was significantly influenced by defacing by modeling their ratings on the same set of images in two conditions: “nondefaced” (i.e., preserving facial features) and “defaced”. In addition, we investigated these biases on automated quality assessments by applying repeated-measures, multivariate ANOVA (rm-MANOVA) on the image quality metrics extracted with MRIQC on the full IXI dataset (N = 581; three acquisition sites). This study found that defacing altered the quality assessments by humans and showed that MRIQC’s quality metrics were mostly insensitive to defacing.

Background: Negative symptoms of schizophrenia, such as lack of motivation, pleasure, social interest, and expression, are key contributors to functional impairments in people with schizophrenia. While psychosocial interventions have demonstrated efficacy, no Food and Drug Administration–approved pharmacotherapies exist specifically to target these symptoms. Evidence-based digital therapeutics (DTx) may offer novel, scalable treatment options to augment existing treatments. Objective: This article describes the study design and methods of a phase 3, multicenter, double-blind, randomized controlled study (CONVOKE). It aims to evaluate the effectiveness and safety of CT-155/BI 3972080 (CT-155), a smartphone-based DTx, as an adjunct to standard-of-care antipsychotic medication in adults with experiential negative symptoms of schizophrenia. Methods: Eligible participants were 18 years or older with a primary diagnosis of schizophrenia receiving stable antipsychotic medication for ≥12 weeks, scored ≥2 on average in at least 2 Clinical Assessment Interview for Negative Symptoms Motivation and Pleasure subscale (CAINS-MAP) domains, and were smartphone owners. Participants were randomized 1:1 to CT-155 (intervention arm) or a digital control app (control arm). CT-155 integrates aspects of multiple evidence-based psychosocial therapeutic techniques, incorporating principles of in-person psychotherapy aimed at targeting negative symptoms. Development of CT-155 was informed by patients during early clinical learning studies using earlier versions of the app. The digital control included elements of the disease educational components of CT-155 and daily digital check-ins. Participants were blinded to their assigned intervention. A blind-to-hypothesis was used so participants appropriately engaged with both apps. Accordingly, participants were informed that they would receive one of 2 interventions under investigation. Investigators, designated site personnel, and central raters were blinded throughout the study. The study comprised a 2-week screening period, 16-week active period, and a 4-week follow-up period. Change in experiential negative symptoms from baseline to Week 16 (primary end point) was assessed using CAINS-MAP (centrally rated). Other study end points included Clinical Assessment Interview for Negative Symptoms Expressivity, Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Dysfunctional Attitudes Scale, Clinical Global Impressions-Severity, and Patient Global Impression of Improvement Scale. Frequency and severity of adverse events were also assessed, as well as engagement and adherence to either app. Results: Study enrollment began in March 2023 and was completed in January 2025. Overall, 457 participants were enrolled across 66 clinical study sites in the United States. Conclusions: We summarize an innovative trial design for CONVOKE, a phase 3 randomized controlled study aimed at assessing the effectiveness, engagement, and safety of CT-155 as an adjunct to standard-of-care for people with negative symptoms of schizophrenia. CONVOKE is the largest-to-date and most robust clinical trial evaluating the effectiveness and safety of a DTx in schizophrenia. The study protocol included a centrally rated primary end point (CAINS-MAP), blind-to-hypothesis, with an appropriately designed digital control. Clinical Trial: ClinicalTrials.gov NCT05838625; https://www.clinicaltrials.gov/study/NCT05838625

Background: Hypercholesterolemia is a significant risk factor for cardiovascular diseases, necessitating effective management strategies. Herbal interventions have gained attention as potential alternative or complementary therapies to conventional lipid-lowering medications. Objective: This systematic review aims to evaluate the effectiveness of various herbal interventions in managing hypercholesterolemia. Methods: A comprehensive literature search will be conducted across multiple databases, including PubMed, MEDLINE, EMBASE, EBSCO, Cochrane Library, DHARA, AYUSH research portal, WHO portal, Shodhganga, and Google scholar as well as dissertations and thesis work available in the public domain and unpublished works from university websites for studies published from January 2020 onward. Randomized controlled trials investigating the impact of herbal interventions on cholesterol levels will be included. The primary outcome is the change in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. Data extraction and quality assessment will be performed independently by 3 reviewers, and discrepancies will be resolved by a fourth reviewer. All statistical analyses will be conducted using the Cochrane Collaboration software program, RevMan Web. Results: Following an initial screening, 96 studies were identified. After removing duplicates, 7 studies were excluded, leaving 89 studies ready for data extraction. The results of these studies will be synthesized and analyzed upon completion. Conclusions: This review aims to synthesize evidence on the potential benefits of herbal interventions in managing hypercholesterolemia. Preliminary findings suggest that specific herbal interventions may contribute to lower cholesterol levels, potentially complementing standard hypercholesterolemia management strategies. The findings will be systematically analyzed and presented upon completion of the review, providing insights into the effectiveness of integrating these interventions into current treatment protocols.

Abstract A seminal study by Triplett provided initial evidence for the social facilitation effect, and over the last century, research has demonstrated this effect across a range of settings. However, despite the importance attributed to Triplett’s study, no research has replicated the original study paradigm. Furthermore, in the context of research advances and methodological rigour, some elements of the original study weaken the validity of the observed findings. We address these critical limitations and replicate the original study, employing a standardized study protocol to minimize potential confounds, such as practice effects. This research reports on 445 school-aged children ( M age = 10.8, SD  = 1.3) who completed the study. As pre-registered in our Stage 1 submission, using a purpose-built apparatus, participants turned a crank to move a marker along a string course between two pulleys. Pairs of participants completed this task four times, twice alone and twice together. Trial order was standardized and balanced to control for possible order/practice effects. In line with Triplett’s original study, we show that participants completed the task faster in the together condition than in the alone condition. We also show interesting variability depending on age and gender, as well as demonstrating “carryover” effects. Thus, we replicate and extend this classic finding, adding to the literature on social facilitation/competitive coaction. In addition, the materials and methods developed here provide a template for future studies to further examine this phenomenon. Protocol registration The Stage 1 protocol for this Registered Report is available at https://osf.io/vsgpq , and appears as accepted in principle by the journal on 10th August 2022.

Introduction Uric acid (UA) is considered as a potential risk factor for coronary heart disease (CHD) and other cardiovascular diseases (CVDs). However, the association between hyperuricemia and the risk of CHD and other cardiovascular outcomes has not been fully clarified. This systematic review and dose-response meta-analysis was conducted to comprehensively the association between hyperuricemia and the risk of CHD or other cardiovascular outcomes in the general population. Methods We systematically searched Medline, Cochrane Library, Embase, and two clinical trial registration databases from inception to June 30, 2025, without restrictions on language or publication status. Only cohort and case-control studies enrolling participants without CHD, other CVDs, or gout at baseline were included. The primary outcome was the association between hyperuricemia and the risk of CHD, and secondary outcomes were the association between hyperuricemia and the risk of fatal and nonfatal CVDs, included CHD death, CVD, CVD death, and myocardial infarction (MI). Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) tool. All statistical analyses were performed using R 4.4.2. We conducted meta-analyses, heterogeneity assessments, publication bias tests, trim-and-fill analyses, subgroup and sensitivity analyses, meta-regressions, and dose-response meta-analyses. The GRADE recommendation was used to evaluate the quality of evidence. Results A total of 42 articles representing 39 individual studies and 1,082,880 participants were included. Among these, 2 articles were assess as “very high risk of bias”, eight as “high risk of bias”, and two as “some concerns”. Hyperuricemia was significantly associated with an increased risk of CHD [HR 1.21 (95%CI 1.14–1.28), p < 0.001, I2 = 34.34%], CHD death [1.20 (1.05–1.36), p = 0.005, I2 = 41.28%], CVD death [1.75 (1.12–2.74), p = 0.014, I2 = 49.48%], and MI [1.23 (1.03–1.47), p = 0.025, I2 = 56.96%]. No significant association was observed for overall CVD risk [1.09 (0.94–1.27), p = 0.245, I2 = 0%]. For each unit increase in serum UA, the risk of CHD, CHD death, CVD, CVD death, and MI increased by 16%, 13%, 12%, 11%, and 7%, respectively. No factors with a significant impact on the results were identified through subgroup analyses or meta-regression. Sex may have a potential influence, but the results were not robust. Further dose-response meta-analysis revealed a linear relationship between higher serum UA and CVD risk, and a U-shaped association between serum UA and CVD mortality in men. The quality of evidence was rated as low for CHD and very low for the other cardiovascular outcomes. Conclusion This systematic review and dose-response meta-analysis provides low- to very-low-quality evidence suggesting that hyperuricemia may be associated with an increased risk of CHD and other fatal or nonfatal CVDs. Trial registration This study was registered in PROSPERO CRD42024538553.

Background: The benefits of physical activity are well established in people with multiple sclerosis (MS); yet, most people with MS are insufficiently active. Although many apps and devices are available to promote physical activity, these are not connected to electronic health records (EHRs), making it difficult for health care providers to prescribe and monitor their patients’ physical activity. The ExerciseRx platform is an innovative cloud-based, Health Insurance Portability and Accountability Act–compliant software platform (app+provider dashboard) that was developed to bridge the gap between consumer activity tracking devices, such as personal smartphones, and the EHR. The ExerciseRx app tracks a patient’s physical activity using their existing personal smartphone and provides a personalized graded progression in step count goals to increase step count gradually and safely over time. The ExerciseRx app also translates the activity data into actionable metrics on a provider dashboard within the EHR that the provider can use to make activity recommendations and monitor patients’ progress; they can also support patients by providing semiautomated weekly feedback and encouragement in meeting physical activity goals.

Background: Abnormal cell growth that can multiply and transfer to other bodily parts is referred to as cancer. Chemotherapy is a standard treatment for cancer patients. During or after treatment, patients may have varying degrees of cognitive impairment caused by the drug, which can negatively impact their quality of life. Cognitive impairment brought on by chemotherapy is one of the most frequent side effects that occur both during and after chemotherapy. Cognitive effects after and during chemotherapy have not been addressed in patients. Objective: To evaluate the effectiveness of cognitive rehabilitation on cognition and quality of life in chemotherapy-induced cognitive impairment. Methods: In this Randomized Control Trial (RCT), 60 subjects with chemotherapy-induced cognitive impairments secondary to any cancer will be randomised into 2 groups by the sequentially numbered opaque sealed envelope approach. The cognitive functions will be measured as the outcome measures, which include all the recall strategies, executive function tasks, information processing speed, and attention. Both groups will receive intervention every day for 4 weeks. Wilcoxon signed the rank test for data analysis, and students paired the “t” test, which will be used to study within-group effects. Mann-Whitney U Test and students Unpaired “t” Test will be used to compare groups at pre-treatment and post-treatment. Results: As of November 2024, we will enrol 60 participants, and the data collection process will start from November 2024November 2025. The expected results of the effect of cognitive rehabilitation on cognition and quality of life in chemotherapy-induced cognitive impairment in cancer patients will be significant, and the expected results will be published at the end week of November 2025. Conclusions: The study design is a framework to plan and test the feasibility of the intervention. The cognitive therapy will improve the cognition in chemotherapy-induced cognitive impairment patients. Trial Registration: Clinical Trials Registry India CTRI/2024/04/065805; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTAyNTE1&Enc=&userName= International Registered Report Identifier (IRRID): DERR1-10.2196/66011

This trial and its outcomes were registered with clinicaltrials.gov on Feb. 7, 2023 under the identifier NCT05718973. The stage 1 protocol for this Registered Report was accepted in principle on 18/09/23. The protocol, as accepted by the journal, can be found at: 10.6084/m9.figshare.24246511.

Background: Chronic pain is one of the most common and debilitating health conditions. Treatments for chronic low back pain typically focus on biomedical treatment approaches. While psychosocial treatments exist, multiple barriers prevent broad access. There is a significant unmet need for integrative, easily accessible, non-opioid solutions for chronic pain. Virtual reality (VR) is an immersive technology allowing innovation in the delivery of behavioral pain treatments. Behavioral skills-based VR is effective at facilitating pain management and reducing pain-related concerns. Continued research on these emerging approaches is needed. Objective: In this randomized controlled trial, we seek to test the efficacy of a self-administered behavioral skills-based VR program as a nonpharmacological home-based pain management treatment for people with chronic low back pain (cLBP). Methods: We will randomize 180 individuals with cLBP to 1 of 2 VR programs: (1) EaseVRx (8-week skills-based VR program); or (2) Sham VR (control condition). All participants will receive a VR headset to minimize any biases related to the technology’s novelty. The Sham VR group had 2D neutral content in a 3D theater-like environment. Our primary outcome is average pain intensity and pain-related interference with activity, stress, mood, and sleep. Our secondary outcomes include patient-reported physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, health utilization, medication use, and user satisfaction. We hypothesize superiority for the skills-based VR program in all of these measures compared to the control condition. Team statisticians blinded to treatment assignment will assess outcomes up to 6 months posttreatment using an approach suitable for the longitudinal nature of the data. Results: The study was approved by the Western Institutional Review Board on July 2, 2020. The protocol (NCT04415177) was registered on May 27, 2020. Recruitment for this study was completed in July 2020, and data collection will remain active until March 2021. In total, 186 participants were recruited. Multiple manuscripts will be generated from this study. The primary manuscript will be submitted for publication in the winter of 2020. Conclusions: Effectively delivering behavioral treatments in VR could overcome barriers to care and provide scalable solutions to chronic pain’s societal burden. Our study could help shape future research and development of these innovative approaches.

Background: Chronic neuropathic pain affects 69% of adults with spinal cord injury (SCI). Medication, as a primary treatment, has insufficient benefits and significant risks for addiction and adverse effects. Of the available mind and body approaches, Qigong is the most accessible for adults with SCI, with evidence for effectiveness in reducing pain. Still, there is insufficient evidence to make recommendations for adults with SCI. Thus, the feasibility of Qigong in SCI needs to be established. We previously demonstrated feasibility in a pilot study, in which 18 non-Hispanic White adults with SCI completed a 12-week remote Qigong program. However, three additional key elements need to be addressed before performing a larger effectiveness study: (1) feasibility and acceptability of Qigong in adults with SCI with health disparities, (2) feasibility of a study design with a control group, and (3) objective outcome measures.

Background: Sexuality is multidimensional and complex, and involves identity development, attraction, and behavior. Heterosexual-identified men who have sex with men (H-MSM) experience sexual identity and behavior discordance, yet it is unknown how H-MSM compare to concordant heterosexual men and gay, bisexual, and queer (GBQ+) men in terms of sexuality constructs. Objective: This study aims to survey adult cisgender men in Canada, the United States, and the United Kingdom to gain greater insights into how demographics, identity development, attraction, behavior, technology use, relationship negotiation and communication skills, and pre-exposure prophylaxis and life satisfaction relate to each other, and then to interview H-MSM for an in-depth follow-up on survey concepts. Methods: Purposive sampling will be used to recruit men via online and offline venues. Data collection will be multifaceted and include an online questionnaire for adult cisgender men and a subsequent interview for H-MSM. The survey will be available in English, French, and Spanish. Structural equation modeling, underpinned by hegemonic masculinity and sexual script theories, will be performed to test the relationships among survey variables. Interpretive phenomenology will be employed on the qualitative data to consider how unique sociocultural factors influence the sexuality and experiences of H-MSM, allowing for similarities and differences across participants to be identified and explored. Results: Data collection began on November 26, 2024, and as of February 2025, data collection remains ongoing. We expect to conclude data collection and data cleaning by mid-summer 2025. Data analysis will begin in fall 2025. Our findings will provide a more nuanced understanding of the identity development, attraction, behavior, relationship negotiation, and technology use of H-MSM in comparison with GBQ+ men and concordant heterosexual men. Conclusions: This research aims to broaden the scope of existing literature and support advancements in interventions and knowledge to support the overall health and well-being of H-MSM. An examination of potential differences among H-MSM, concordant heterosexual men, and GBQ+ men aims to improve the understanding of H-MSM as a distinct population, without dismissing them as closeted GBQ+ men. This study aims to provide key insights into avenues for research and practice with men whose sexuality and sexual behaviors may be outside of commonly accepted norms.

Background: The incidence of chronic diseases associated with physical inactivity is on the rise, being one of the leading risk-increasing factors for early death rates throughout the world. Often, physical activity interventions fail to deliver sustained adherence over time due to limiting tailoring to individual baseline characteristics, leaving out contextual changes over time. One solution for this issue may be the use of adaptive interventions relying on contextual multiarmed bandits, a type of reinforcement learning algorithm, that can use baseline and contextual individual data to personalize aspects of the intervention, such as developing personalized workout plans. Objective: The main objectives of this study are (1) to determine the effectiveness of contextual bandits for automated goal setting in the context of a web-based physical activity intervention, (2) to understand the role of user characteristics impacting ideal workout schedules based on adherence to predetermined goals, and (3) to explore the influence of user autonomy on recommendation effectiveness. Methods: We developed a protocol for a web-based adaptive intervention trial to investigate the effectiveness of goal recommendation (task difficulty) based on reinforcement learning. The web application (named Apptivate) creates workout routines with 3 different difficulty levels, changing the total workout duration as well as rest times between exercises. Physical activity professionals validated the routine design, ensuring that workouts match recommended guidelines for healthy adults. An initial pilot was conducted, aiming for 800 university students to test the web application for 1 week, to provide initial data to calibrate the algorithm as well as overall feedback for the web application. For the main study, a total of 500 university students will be recruited to participate for 40 days during early 2026. Participants will be divided into 3 groups: user choice (no recommendation), user choice with automated recommendations (contextual bandits), and automated plans without choice. Results: The pilot was conducted in September 2025. Data analysis for the pilot is undergoing, and the main study is planned for early 2026. Our main statistical analysis includes a direct comparison (paired tests) between success rates across intervention arms, as well as by difficulty level and individual characteristics. Conclusions: Physical activity maintenance is key to achieving long term health goals. Tailored digital interventions are promising strategies for physical activity adherence, but personalization often fails to consider dynamic contextual changes. The proposed protocol for a physical activity intervention using adaptive experimentation can provide robust causal inference on the role of choice versus autonomy when goal difficulty is tailored under an adaptive data-driven approach.

Background: Diabetic retinopathy (DR), a leading cause of preventable blindness among working-age adults, leads to worse health outcomes among Black, Latine, and individuals with lower income in comparison to other ethnic, racial, and socioeconomic groups in the United States. Objective: We aim to engage community members directly to identify barriers and facilitators of DR screening and co-design a digital health tool that is accessible, user-friendly, and community-responsive. Methods: We conducted focus groups with individuals from the Greater New Haven, Connecticut area, aged 18 years or older, and diagnosed with diabetes to (1) conduct a comprehensive disease-management needs assessment and (2) inform the development of a community-responsive digital health tool to optimize DR education and to increase access to DR screening in high-risk populations. We transcribed the focus group interviews, used rapid qualitative analysis to generate themes, and completed affinity mapping to identify content and features for a digital health tool for preventing blindness from DR. Results: We recruited and interviewed 19 individuals (13/19, 68% female; 9/19, 47% Black; 5/19, 26% Hispanic; 2/19, 11% Native American or Alaska Native) for 4 focus groups. Over 94% (18/19) had access to smart devices other than a computer. Participants self-reported mean hemoglobin A1c of 6.77 (SD 1.93). Approximately 58% (11/19) of the participants completed some college. Frequently occurring themes (&gt;30) obtained from coding contextual interviews were desired app attributes such as options for customization, covering topics such as, the mental impact of living with diabetes, informal support (eg, peer support), diabetes education, barriers to controlling blood sugar and maintenance of health, dietary guidance, and notifications. We created high-fidelity wireframes incorporating key features. Next, we will iteratively design a prototype with community feedback. Conclusions: We anticipate that this study will characterize the experiences of people living with diabetes. Using a community-led approach,we will continue to analyze the data that will generate insights regarding the key features, content, and benefits that are most important for the creation of a digital health tool for DR prevention.

Background: Almost a third of Australian adults are living with obesity, yet most cannot access medical nutrition therapy from dietitians, that is, the health professionals trained in dietary weight management services. Across the health system, primary care doctors readily identify people who may benefit from weight management services, but there are limited referral options in the community. Dietitians are trained to provide evidence-informed dietary treatment of overweight and obesity but are underutilized and underresourced. The chat2 (Connecting Health and Technology 2) trial will test combining new technologies for dietary assessment with behavior change techniques to improve outcomes for people living with obesity. Objective: This study aimed to compare the effectiveness of a 1-year digital dietary intervention, with standard care on body weight reduction and improved diet quality, in adults living with obesity delivered by dietitians in a primary care setting. Methods: This randomized controlled trial will compare a 1-year, digitally tailored, feedback dietary intervention with a control group in 430 adults living with obesity (BMI≥30 to ≤45 kg/m2). Participants will be recruited by letters sent to individuals randomly selected from the electoral roll and supplemented by hospital site posters, newsletters, and unaddressed mailbox delivery postcards sent to residential street points. The primary outcome is change in body weight, measured face-to-face at a baseline, 6 months, and 12 months. A 4-day, image-based dietary assessment tool (mobile Food Record) will be used to measure diet quality score. Secondary outcomes include diet quality score; dual-energy absorptiometry body composition; and total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, glycated hemoglobin, and fasting glucose levels. The intervention group will receive 8 video counseling sessions with a trained dietitian delivered over 12 months to support dietary behavior change and relapse prevention. The trial is unblinded. Both groups will receive feedback on their clinical chemistry and dual-energy absorptiometry scans at each time point. Results: Participant recruitment commenced in July 2023 and ended in August 2024. Data analysis will commence in 2025, with the anticipated publication of results in 2026. Conclusions: If found to be effective, the results of this randomized controlled trial will support the delivery of effective, evidence-based weight management advice using new technologies. Improving community access to high-quality dietetic services will ensure more effective use of the dietetic workforce to improve outcomes for people living with obesity. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12622000803796; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383838

Background: Significant advances in digital technologies have meant that health care data can be collected, stored, transferred, and analyzed for research purposes more easily than ever before. Participant-centric initiatives (PCI) are defined as “tools, programs, and projects that empower participants to engage in the research process” using digital technologies and have the potential to provide a number of benefits to both participants and researchers, including the promotion of public trust in medical research, improved quality of research, increased recruitment and retention, and improved health care delivery. Objective: The main objective of this scoping review is to describe the extent and range of PCIs across the United Kingdom, United States, and Japan that are designed to facilitate medical research. Methods: The methodological framework described by Levac et al will be applied to this scoping review. We will search electronic databases (MEDLINE, EMBASE, PsychINFO, Cumulative Index to Nursing, and Allied Health Literature and CiNii), grey literature sources, Internet search engines (Google and Bing), and hand search key journals and reference lists of relevant articles. All digital tools and programs will be eligible for inclusion if there is a description of key features and functions that fall within the parameters of a PCI. Only those that play a role in medical research will be included. Results: Preliminary searches conducted in MEDLINE and EMBASE retrieved 1820 and 2322 results, respectively. The scoping review will be completed by January 2018. Conclusions: The scoping review will be the first to map the extent and range of PCIs currently available across the United Kingdom, United States, and Japan, and will be the first review to contribute to a better understanding of what PCIs patients may benefit from. Researchers and practitioners will be able to use information in this review as a guide for patients and also as a guide for the development of future tools and programs. The results will be disseminated through a peer-reviewed publication and conference presentations.

Stressors like test anxiety are known to decrease memory retrieval, whereas retrieval practice is the phenomenon that actively recalling information from memory enhances memory. Evidence suggests retrieval practice can protect memory against the negative effects of stress on memory (Agarwal et al., 2014; Smith &amp; Thomas, 2018), however the findings are mixed (Yang et al., 2020). Understanding whether retrieval practice maintains memory performance under stress could transform memory resilience and lead to new cognitive interventions. This raises the need for a meta-analytic summary of the literature to understand the effects of retrieval practice on memory in relation to stressors. In this registered report, we conducted a meta-analysis (k = 10, n = 908) on the impact of stress following learning with retrieval practice from 2006&ndash;2024 using databases and other information sources. We found a positive effect of retrieval practice in stress conditions, Hedges&rsquo; g = 0.45, 95% CI [0.17, 0.72] with a random-effects two-level model, suggesting retrieval practice is more beneficial than restudy during stress. Significant heterogeneity was observed along with a moderate risk of bias, yet little evidence for publication bias. We did not find significant moderators in this sample. Future studies should be conducted with sufficiently powered samples and using other types of control, or non-retrieval practice, strategies to better understand the protective effects of retrieval practice on memory following stress. We registered our meta-analysis, with datafile, code and supplementary here: https://osf.io/jwx4f/.

Background: People of color (POC) who experience race-related stress are at risk of developing mental health problems, including high levels of stress, anxiety, and depression. Mindfulness meditation may be especially well suited to help POC cope, given its emphasis on gaining awareness and acceptance of emotions associated with discriminatory treatment. However, mindfulness meditation rarely reaches POC, and digital approaches could reduce this treatment gap by addressing traditional barriers to care. Objective: This study will test the effectiveness of a self-directed app-based mindfulness meditation program among POC who experience elevated levels of race-related stress. Implementation outcomes such as treatment acceptability, adherence, and satisfaction will be examined. Methods: Participants (n=80) will be recruited online by posting recruitment materials on social media and sending emails to relevant groups. In-person recruitment will consist of posting flyers in communities with significant POC representation. Eligible participants will be block randomized to either the intervention group (n=40) that will complete a self-directed 4-week mindfulness meditation program or a wait-list control condition (n=40) that will receive access to the app after study completion. All participants will complete measures at baseline, midtreatment, and posttreatment. Primary outcomes include changes in stress, anxiety, and depression, and secondary outcomes constitute changes in mindfulness, self-compassion, rumination, emotion suppression, and experiential avoidance. Exploratory analyses will examine whether changes in the secondary outcomes mediate changes in primary outcomes. Finally, treatment acceptability, adherence, and satisfaction will be examined descriptively. Results: Recruitment began in October 2021. Data will be analyzed using multilevel modeling, a statistical methodology that accounts for the dependence among repeated observations. Considering attrition issues in self-directed digital interventions and their potential effects on statistical significance and treatment effect sizes, we will examine data using both intention-to-treat and per-protocol analyses. Conclusions: To our knowledge, this will be the first study to provide data on the effectiveness of a self-directed app-based mindfulness meditation program for POC recruited based on elevated race-related stress, a high-risk population. Similarly, meaningful clinical targets for POC affected by stressors related to race will be examined. Findings will provide important information regarding whether this type of intervention is an acceptable treatment among these marginalized groups. Trial Registration: ClinicalTrials.gov NCT05027113; https://clinicaltrials.gov/ct2/show/NCT05027113

Background: Cardiovascular diseases (CVDs) are a leading cause of death and disability worldwide. For people living with CVD, clinical guidelines recommend ongoing self-care such as symptom monitoring, medication adherence, and lifestyle modifications. However, many people struggle to engage in this due to the complexity of disease management, limited understanding, and a lack of cultural support. Conversational agents (CAs) offer a solution by providing artificial intelligence–driven, voice-based support that enables human-like communication. While many CAs and digital interventions are good for people with CVDs, they are for mainstream populations and overlook culturally and linguistically diverse communities. Objective: This study outlines the protocol for pilot testing the feasibility and usability of Diaspora Engaged Self-Care Intervention and Heart (DESI-Heart) program, to support self-care management among Indian diaspora populations with CVDs in Australia over an 8-week intervention period. The formative development of DESI-Heart is also described. Methods: We integrated the Double Diamond Model and the ecological validity model to develop our DESI-Heart program. First, we co-designed the program with end users, who identified 4 key goals for engagement with self-care through culturally and linguistically appropriate approaches. Based on these priorities and ideas, we developed specific goals, including (1) medication reminders, (2) daily exercise guidance, (3) diet buddy, and (4) guided meditation. Participants will access the DESI-Heart program through a web-based CA, available on smartphones, laptops, or PCs. Based on their preferred timing, individuals will receive links to access specific components of the program corresponding to each goal. These links will be sent to participants via SMS or email, depending on their preference. A single-arm prepost pilot trial (N=28) will be conducted to evaluate the feasibility and usability of the DESI-Heart program among Indian adults living in Australia with CVDs. The primary outcome will assess feasibility indicators, including recruitment, engagement, and usability, while secondary outcomes will examine changes in self-care behaviors and quality of life. Results: The DESI-Heart program received ethics approval in July 2024. Recruitment for the pilot trial is scheduled to begin in June 2025 and conclude by September 2025, with participant follow-up expected to be completed by the end of December 2025. All 28 participants have been recruited, and data analysis will be conducted once follow-up is finalized. Conclusions: We have co-designed and developed the DESI-Heart program, a culturally and linguistically appropriate self-care intervention aimed at supporting Indian adults with CVD living in Australia. The next step is to conduct a pilot study to assess the feasibility and usability of DESI-Heart, which will inform the design of a larger evaluation trial. DESI-Heart has the potential to complement existing health services by helping individuals with CVD manage their condition within the community, while acknowledging their cultural backgrounds and language preferences.

Background: HIV/AIDS is an epidemic in 190 countries, with Indonesia having more than half a million people living with the virus. Risk factors include risky sexual activity and alternating needle usage. The majority of cases are young adults (18-30 years old). The Indonesian National HIV/AIDS strategy aims to reduce new cases to less than a thousand per year. Nowadays, effective prevention involves avoiding free sex and adopting healthier lifestyles. Objective: This research aims to explore young adults’ needs, perceptions, and cultural aspects of HIV/AIDS prevention, develop the intervention model, analyze its effectiveness, and examine its effect on HIV prevention behavior. Methods: We will conduct the study in three phases: qualitative research, model development, and quantitative research. In the first phase, we will use descriptive phenomenology and forum group discussion (FGD) to collect data from young adults and stakeholders in Batang and Pekalongan regencies. The second phase will develop a motivation model for HIV/AIDS prevention using culture-based communication (MK-U) through website media. We will design the model in consultation with an IT team and experts to ensure its suitability. The third phase will involve a pre-post-test with a control group quasi-experiment involving young adults aged 20–30 years old in Batang and Pekalongan districts. The intervention group will receive culture-based motivational interviewing, while the control group will receive standard counseling. We will analyze the data using a generalized linear model (GLM) and multivariate analysis of variance (MANOVA). Results: We expect to develop the MK-U model for HIV prevention behavior among young adults. In 2025, we will implement a community-based nursing research program for the MK-U model to prevent HIV/AIDS. Conclusions: In this research, we will compare the results with similar studies, which will benefit program implementers and policymakers in both regions and enhance the effectiveness of HIV prevention programs.

Background: Medical, psychiatric-psychosomatic facilities are confronted with a variety of daily challenges that affect working conditions, the mental health of employees and the quality of patient care. This project focuses on the work-related challenges faced by healthcare professionals in psychiatric-psychosomatic clinics in Germany. Objective: Therefore, the aim of the current research is to investigate the interactions between individuals and their social environment, identify psychological and organizational challenges and job demands to use these findings to inform the development of a participatory, evidence-based intervention. Methods: This two-phase research is grounded in the job demands-resources model (JD-R). Study phase one (needs assessment) employs a cross-sectional online survey with healthcare professionals in German psychiatric-psychosomatic clinics to assess job demands, resources, and outcomes in a target sample of 600 participants (power analysis). Study phase two (co-design of a training) involves co-creatively designing an intervention based on survey findings through participatory workshops with at least 20 participants. Analyses include regression and moderation tests (SPSS), and qualitative data analysis to co-design training. Results: The recruitment of participants is planned to be finished by October 2025. The co-designing of workshops (phase two) will be started in February 2026. As this is a study protocol, results are not available yet. Conclusions: This current research examines the work-related challenges faced by healthcare professionals in psychiatric-psychosomatic clinics. It is expected that burnout, engagement, and psychological safety will likely emerge as central mediating and moderating variables. As the findings of phase one serve as a basis for the development of an intervention this research seeks to improve the well-being of healthcare professionals in psychiatric-psychosomatic institutions sustainably. Clinical Trial: ClinicalTrials.gov NCT06867601; https://clinicaltrials.gov/study/NCT06867601

Background: The COVID-19 pandemic impacted trust in public health, medical care, scientific, and governmental institutions; this influenced health, health-seeking behaviors, and adherence to public health measures. Understanding how trust evolves is necessary for informing future public health crisis management and strategies. Rebuilding public trust is key to pandemic preparedness worldwide. This research protocol examines these trust dynamics, their determinants, and their implications. Objective: This study aimed to investigate the evolution of public trust in scientists, public health and medical care institutions, governments, and social and personal networks during the COVID-19 pandemic. It sought to identify key factors contributing to trust maintenance or erosion, particularly in marginalized and minority communities, and understand the impact of trust level on public health adherence. Methods: A sequential, explanatory mixed methods approach was implemented, consisting of an initial quantitative survey followed by qualitative interviews. The nationwide representative survey included 5607 Canadian residents as of May 2024. The questionnaire assessed trust in 6 key trust sources before and during the pandemic: provincial and federal governments, public health authorities, medical care providers, health scientists, and social and personal networks. To complement, 41 qualitative interviews were conducted to understand participants’ lived experiences, perceptions, and how trust played into both. Data have been analyzed using quantitative statistical techniques and qualitative phenomenological analysis, and the results have been integrated to derive comprehensive insights. All phases of data collection and analysis were finalized by early 2025. The project then advanced to paper preparation, dissemination at national conferences, and knowledge-translation activities, including the report development and public-facing outputs, scheduled for completion in end-2025. Results: This Canadian survey included participants from all 10 provinces and 2 territories; the provinces and territories’ samples matched the proportions of each in the overall Canadian population. Age and sex or gender were well distributed across the sample. Additionally, 18.6% (1040/5607) identified as an ethnic minority, 12.7% (710/5607) identified as Indigenous, including 7.2% (403/5607) First Nations, 4.8% (270/5607) Métis, and 0.4% (25/5607) Inuit. Fifty-five percent (3094/5607, 55.2%) had received at least 1 dose and planned to stay up to date with booster recommendations, while 36.6% (2052/5607) were vaccinated but did not intend to receive additional doses. A small percentage, 0.7% (39/5607), had not yet been vaccinated but were open to it, whereas 6.4% (359/5607) had not received a vaccine and did not plan to take a vaccine. Conclusions: The COVID-19 pandemic has underscored the critical role of trust in public health behavior and crisis response. This study explores how consistent, transparent communication and equity-driven policies may contribute to maintaining public trust, particularly among marginalized communities. By examining trust dynamics and identifying potential disparities, this study aims to inform evidence-based public health strategies and improve preparedness for future health emergencies. Trial Registration:

Background: The COVID-19 pandemic challenged families, youth, and frontline workers, including childcare providers. Studying lived experiences before, during, and near the pandemic’s end from multiple perspectives provides a more holistic and deeper understanding of its effects and impacts. Objective: This study investigated how parental, childcare provider, and youth stress, mental health, and role overload relate to individual coping and family functioning, as well as vaccine attitudes and uptake patterns among youth, parents, and childcare providers. Information learned from this investigation will inform policy and messaging for future public health crises. Methods: This study is an explanatory sequential mixed methods study designed to capture the voices of parents of children younger than 18 years of age, childcare providers, and youth aged 12-17 years through surveys and interviews. This retrospective cross-sectional study began with a web-based survey that included demographic questions and validated scales to assess personal well-being, household and family dynamics, behavioral problems, and vaccination-related perceptions, attitudes, and behaviors. Open-ended responses about pandemic experiences for themselves and their families were included. A subsample of parents, youth, and childcare providers was selected for in-depth interviews about their pandemic-related experiences. Descriptive statistics were used to summarize demographic characteristics, and internal consistency was assessed for all survey measures using Cronbach α. Future studies will use inferential statistical techniques to analyze survey measures, thematic analysis for open-ended survey responses and interview data, and mixed methods data integration to synthesize quantitative and qualitative findings. Results: Data collection for the study began in August 2022 and finished in August 2023. Data analysis is currently in progress to address research questions, and study preparation and dissemination efforts are underway. A total of 506 adults and 93 youths answered a study survey, and 45 adults and 21 youths completed in-depth interviews. Among the 506 adults, 166 were childcare providers. The adult sample had a mean age of 42.8 (SD 9.15) years and was predominantly female (467/506, 92.3%), with 9.7% (49/506) identifying as Black, 4.7% (24/506) as Hispanic, and 81.2% (411/506) being parents of children aged 17 years or younger. The youth sample had a mean age of 14.5 (SD 1.63) years, and 55.9% (52/93) were female, 6.4% (6/93) were Black, and 17.2% (16/93) were Hispanic. Several dyads and triads participated. The sample included 42 parent-child dyads, 3 parent-parent dyads, 2 parent-parent-child triads, and 21 parent-child-child triads. Conclusions: These data will be used to understand the diverse experiences of families, youth, and childcare providers during and after the COVID-19 pandemic. This includes successful and unsuccessful adaptations, responses to policies and mandates, and the unmet needs for health messaging, programs, policies, and services. This research aims to guide the development of effective policies and public health communication, fostering scalable and sustainable messaging resources.

Background: Driving performance involves multiple underlying components of psychomotor functioning, such as attention, executive functions, and vehicle control. While the effects of acute medical marijuana and prescription opioid intoxication are known, how long-term use of medical marijuana under real-world conditions affects driving performance is unknown. Additionally, there are numerous ongoing physical and cognitive changes that affect driving performance with age. Given the proliferation of medical marijuana and prescription opioid use in adults aged 50 years and older, the prevalence of polypharmacy, and declining functional abilities, it is imperative to understand the long-term effects of daily medical marijuana use. Further, we need to understand how co-occurring use of medical marijuana and prescription opioids, in the presence of comorbidities such as chronic pain, affects real-world driving outcomes. Objective: This study aims to document the observational trial protocol. The primary goal of this study is to identify the effects of daily long-term (ie, use for &gt;12 months daily or most days of the week) medical marijuana use on driving performance outcomes using an open-road driving performance task under real-world conditions in adults aged 50 years and older who endorse chronic or severe nonmalignant pain and to examine the combined effect of daily long-term medical marijuana use and prescription opioid use on driving outcomes. A secondary goal is to qualitatively explore self-regulation of medical marijuana and prescription opioid use in this population. Methods: We plan to test medical marijuana use as the exposure variable in adults aged 50 years and older on an open-road driving task performance as the primary outcome. The study will detail tetrahydrocannabinol exposure through ecological momentary assessment and urinalysis and will compare performance with a race-sex–matched group of non–marijuana users. Results: This study is funded by a grant from the National Institute on Drug Abuse (5R01DA057965). Recruitment began on May 19, 2025. As of November 2025, a total of 30 participants had been enrolled. Recruitment is anticipated to be completed by 2029. Publication of the complete results and data from this study is expected by 2030. Conclusions: Data from this study will identify the effects of long-term medical marijuana use and the combined effect of that use with prescription opioids to develop risk screening protocols and intervention targets for this population. The development and dissemination of screening and intervention guidelines will be the next step in this work. Trial Registration: ClinicalTrials.gov NCT06995937; https://www.clinicaltrials.gov/study/NCT06995937

Background: For many years, clinicians have been seeking for objective pain assessment solutions via neuroimaging techniques, focusing on the brain to detect human pain. Unfortunately, most of those techniques are not applicable in the clinical environment or lack accuracy. Objective: This study aimed to test the feasibility of a mobile neuroimaging-based clinical augmented reality (AR) and artificial intelligence (AI) framework, CLARAi, for objective pain detection and also localization direct from the patient’s brain in real time. Methods: Clinical dental pain was triggered in 21 patients by hypersensitive tooth stimulation with 20 consecutive descending cold stimulations (32°C-0°C). We used a portable optical neuroimaging technology, functional near-infrared spectroscopy, to gauge their cortical activity during evoked acute clinical pain. The data were decoded using a neural network (NN)–based AI algorithm to classify hemodynamic response data into pain and no-pain brain states in real time. We tested the performance of several networks (NN with 7 layers, 6 layers, 5 layers, 3 layers, recurrent NN, and long short-term memory network) upon reorganized data features on pain diction and localization in a simulated real-time environment. In addition, we also tested the feasibility of transmitting the neuroimaging data to an AR device, HoloLens, in the same simulated environment, allowing visualization of the ongoing cortical activity on a 3-dimensional brain template virtually plotted on the patients’ head during clinical consult. Results: The artificial neutral network (3-layer NN) achieved an optimal classification accuracy at 80.37% (126,000/156,680) for pain and no pain discrimination, with positive likelihood ratio (PLR) at 2.35. We further explored a 3-class localization task of left/right side pain and no-pain states, and convolutional NN-6 (6-layer NN) achieved highest classification accuracy at 74.23% (1040/1401) with PLR at 2.02. Conclusions: Additional studies are needed to optimize and validate our prototype CLARAi framework for other pains and neurologic disorders. However, we presented an innovative and feasible neuroimaging-based AR/AI concept that can potentially transform the human brain into an objective target to visualize and precisely measure and localize pain in real time where it is most needed: in the doctor’s office. International Registered Report Identifier (IRRID): RR1-10.2196/13594

Background: Background: The Symptom iNput Clinical (SYNC) system was developed to enhance the timely reporting of Head and Neck Cancer (HNC) symptoms and to ensure that high-risk patients receive faster diagnoses. A key feature of the system is a digital questionnaire co-designed with patient representatives to accommodate varying levels of digital literacy. The system integrates a validated algorithm that assigns risk scores to categorise cases as low or high risk, and a dashboard that supports clinicians by providing them with patient reports. However, the development process encountered challenges that necessitates a systematic evaluation of the process, roles, and experiences of team members. Objective: Objective: This study aims to identify challenges faced during development, how these challenges were addressed, and the implications for future digital health innovations. Methods: Methods: A qualitative single-case study approach will be employed, focusing on individuals involved in the SYNC system’s development. Participants will be selected using a combination of purposive and snowball sampling to ensure diverse perspectives, using meeting minutes and recommendations from key stakeholders. A total of 8 to 12 participants will be interviewed, representing clinical, research, and IT roles. Data collection will involve semi-structured interviews which will be conducted through Microsoft Teams. The interviews are expected to last between 40–60 minutes each. These interviews will be audio-recorded, transcribed, and analysed using framework analysis in Dedoose. Actor-Network Theory (ANT) will guide the analysis by mapping interactions between human and non-human actors, such as developers, clinicians, and technological tools, to understand how they influenced the project’s outcomes. Participant confidentiality will be maintained through data encryption, de-identification, and secure storage. Results: Expected Results: The study anticipates identifying key barriers and facilitators in the SYNC system’s development, including technical, organisational, and collaboration-related challenges. The findings are expected to provide a detailed account of the challenges encountered, such as delays, security concerns, and coordination issues, an insight into how these challenges were mitigated and lessons learned and recommendations for improving digital health technology development, including best practices for co-design, technical integration, and stakeholder engagement. Conclusions: Conclusion: This case study will provide valuable insights into the complexities of developing digital health technologies, particularly in collaborative, multi-stakeholder environments. Documenting the challenges encountered in the SYNC system’s development will contribute to best practices in digital health innovation.