Background: Cyberbullying victimization is prevalent and closely linked to mental health problems. However, existing research, often limited by cross-sectional designs and a focus on direct relationships, has yielded inconsistent results. Furthermore, the biological mechanisms underlying the relationship between cyberbullying victimization and psychopathological outcomes remain largely unclear at present. Objective: This retrospective cohort study aimed to explore the longitudinal associations among cyberbullying victimization, inhibitory control, brain activation during error processing, and mental health problems among adolescents. Methods: We curated the clinical, behavioral, and neuroimaging data (551/1186, 46.5% girls; 9-10 years at baseline) from the Adolescent Brain Cognitive Development study, a nationally representative cohort established through school-based probability sampling (selected factors included gender, race/ethnicity, socioeconomic status, and urbanicity). Participants were assessed by the cyberbullying question, the functional magnetic resonance imaging stop signal task for inhibitory control and error processing, and the Child Behavioral Checklist for externalizing and internalizing problems at 2-year (T1) and 4-year follow-up (T2). Linear mixed models were used to examine the retrospective longitudinal associations between these clinical, behavioral, and neuroimaging factors. Results: Linear mixed models showed that victims of cyberbullying at T1 exhibited significantly greater externalizing problems at T2 (β=0.25, 95% CI 0.06-0.45, PFDR=.02), but not for internalizing problems (β=–0.01, 95% CI –0.20 to 0.19, PFDR=.99) or deficits in inhibitory control (Correct Stop Rate: β=–0.02, 95% CI –0.26 to 0.21, PFDR=.85; Stop Signal Reaction Time: β=–0.07, 95% CI –0.27 to 0.13, PFDR=.85). Furthermore, cyberbullying victimization at T1 contributed to higher activation in the bilateral superior parietal gyri (left: β=0.36, 95% CI 0.10-0.61, PFDR=.04; right: β=0.34, 95% CI 0.08-0.59, PFDR=.04), right inferior parietal gyrus (β=0.32, 95% CI 0.07-0.57, PFDR=.04), and right posterior cingulate cortex (β=0.34, 95% CI 0.09-0.60, PFDR=.04) during error processing at T2. However, these neural alterations did not significantly mediate between cyberbullying victimization at T1 and externalizing problems at T2. Conclusions: This longitudinal functional magnetic resonance imaging study investigates neural correlates of cyberbullying victimization in adolescents. By extending prior research that has relied primarily on cross-sectional or behavioral data, this research demonstrates that this form of victimization is associated with altered neural activation during error processing in later development. The pattern of nonsignificant impairment in inhibitory control and mediation to externalizing problems suggests that these neural impacts may be better characterized by a state of heightened sensitivity and compensatory engagement than by direct damage. Overall, this study points to the error-processing network as a potential target for cognitive interventions and establishes a foundation for further exploration of other neural mechanisms between cyberbullying victimization and mental health outcomes. Trial Registration:

Date Submitted: Feb 15, 2026. Open Peer Review Period: Feb 17, 2026 - Apr 14, 2026.

Background: Hospital-Based Violence Intervention Programs (HVIPs), based in Emergency Departments (EDs), have been proposed as a public health response to violence. These programs address the underlying reasons why patients are exposed to violence. In addressing any underlying modifiable risks and vulnerabilities HVIPs can reduce patients’ exposure to violence and therefore subsequent unplanned attendance into ED. Objective: The objectives of this #Study are to (1) assess whether patient involvement with a HVIP reduces the likelihood of unscheduled ED reattendance, (2) determine whether the presence of the HVIP improves ascertainment of violence in ED attendances, and (3) derive the costs of the HVIP and compare those to the benefits of the intervention and understand whether the HVIP represents value for money from a health service perspective. If an effect is observed, then models will estimate the health impacts, costs and potential savings over a longer time (eg, 10 years) period and for a national roll-out. Methods: ED patients are eligible for inclusion in the evaluation if they are normally resident in Wales, United Kingdom, aged 11 years and older. A controlled longitudinal natural experiment will be undertaken. The primary outcome is derived from the Emergency Department Dataset, routinely collected for all EDs in Wales, and is subsequent unplanned ED attendance. Case patients will be matched to control patients attending EDs without an HVIP. Analysis will derive the hazard rate for subsequent unplanned ED attendances using recurrent event analysis. The total monthly count of patients identified as attending because of violence in intervention EDs will be compared to the total count of Welsh control EDs in an interrupted time-series analysis to determine whether HVIPS increase violence ascertainment. To determine whether referral, versus no referral, to the HVIP represents value for money, we will undertake a cost-effectiveness analysis from the perspective of the National Health Service. The approval to access and analyze data housed in the Secure Anonymized Information Linkage (SAIL) databank, an ISO (International Organization for Standardization) 27001 certified and UK Statistics Authority accredited secure data environment, was granted by the SAIL independent Information Governance Review Panel (Ref: 1421). Findings will be presented at local, national, and international conferences and disseminated by peer-reviewed publication. Results: Design inputs arising from public patient involvement and engagement (PPIE) are reported. As a #Protocol, no further results are available. Conclusions: Novel methods are developed to provide the first robust evaluation of Emergency Department Violence Intervention Programs (EDVIPs). Trial Registration: ISRCTN Registry ISRCTN68945844; https://www.isrctn.com/ISRCTN68945844?q=68945844&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10

Background: Patients frequently search for health information online and value physician support in evaluating and interpreting their findings, yet many hesitate to share their online searches with their physicians. This hesitation hinders shared decision-making and compromises patient care. While extensive research has examined patients’ online health information–seeking behaviors, little has focused on patients’ disclosure of this information to their physicians during consultations. Objective: Guided by the Health Empowerment Model and the Linguistic Model of Patient Participation in Care, this study aims to (1) identify distinct patient profiles based on eHealth literacy and psychological health empowerment levels, (2) examine how these patient profiles differ in online health information seeking and disclosure to physicians, and (3) investigate whether patient-centered communication (PCC) promotes information disclosure and whether this effect varies by patient profile. Methods: This cross-sectional study surveyed 2001 Chinese participants recruited through convenience sampling. Patient profiles were identified using k-means cluster analysis with standardized z scores of eHealth literacy and psychological health empowerment. Differences between profiles in information behaviors were examined using 1-way Welch ANOVA, chi-square tests, and pairwise comparisons. Regression analyses examined the association between PCC and disclosure of online health information. Moderation analyses using the Hayes PROCESS macro assessed whether this association varied across patient profiles. Results: Four distinct patient profiles were identified: effective self-managers (996/2001, 49.8%), moderate-needs dependent patients (408/2001, 20.4%), high-needs patients (68/2001, 3.4%), and dangerous self-managers (529/2001, 26.4%). Profiles differed significantly in information-seeking intentions (F3,289=62.09; P

Background: The convergence of digital health and One Health represents an emergent paradigm in global health governance. While widely discussed in high-income settings, there is limited understanding of how this convergence is conceptualized in the Global South, particularly when viewed through a gender- and equity-sensitive foresight lens. Objective: This study aimed to map and classify expert discourse on digital health, One Health, and their convergence in the Global South using latent semantic analysis, with particular attention to structural drivers, emerging issues, weak signals, and gendered patterns of anticipation. Methods: A 3-round online Delphi survey was conducted with 45 experts from 19 countries across the Global South. Open-ended responses were analyzed using latent semantic analysis and stratified by gender. A foresight framework was applied to categorize topics as structural drivers, emerging issues, or weak signals, based on their temporal persistence, salience, and consensus. Results: In digital health, structural drivers included the systemic integration of digital technologies into public health systems, strategic alignment, and infrastructure development. Emerging issues comprised the adoption of artificial intelligence, chronic disease management via mobile health, and concerns about digital inclusion and interoperability. Weak signals included feminist digital ethics, trust in digital systems, and relational accountability—more frequently emphasized by female experts. In One Health, structural drivers were centered on intersectoral coordination, ecological integration, and the institutionalization of health-environment frameworks. Emerging issues encompassed anticipatory risk governance, food system sustainability, and the integration of environmental and population-level data. Weak signals included indigenous knowledge systems, subnational antimicrobial resistance governance, and structural underinvestment in ecological public health, with gendered divergence in framing. In the convergence discourse (digital health and One Health), structural drivers focused on the integration of digital surveillance systems, data infrastructures, and health information platforms to operationalize One Health. Emerging issues included climate-triggered system redesign, artificial intelligence and ecological monitoring, and the governance of cross-sectoral data. Weak signals pointed to algorithmic bias in zoonotic prediction, digital sovereignty in environmental health, and feminist critiques of convergence—all thematically rich but peripheral in consensus. Conclusions: This study revealed a multilayered and gender-influenced foresight architecture shaping the future of digital health and One Health in the Global South. Structural drivers denote maturing domains of implementation, while emerging issues and weak signals highlight latent, often overlooked opportunities and tensions. Incorporating equity-sensitive and gender-aware foresight methods is essential for crafting inclusive and anticipatory health governance strategies.

Background: Artificial intelligence (AI) health care chatbots are gaining widespread adoption worldwide. It is imperative to understand the service quality of AI health care chatbots. However, there is limited guidance on how to comprehensively evaluate their service quality. Objective: This study aimed to develop an index system based on the SERVQUAL framework for evaluating the service quality of AI health care chatbots. Methods: An initial indicator pool was compiled through a comprehensive literature review and consultations with 4 experts. These indicators were mapped and categorized into 5 domains adapted from the SERVQUAL framework. The experts were recruited from hospital, university, and health commission settings by purposive sampling. The service quality index system was identified using a 2-round Delphi process, which included a virtual meeting between the 2 rounds. In the third round, indicator weights within each quality domain and subdomain were determined using the analytic hierarchy process. Results: There were 26 indicators identified in the literature, based on which the 2-round Delphi process was conducted. A total of 20 experts were invited. The response rates in both rounds of Delphi and the analytic hierarchy process were 100%, and the authoritative coefficients were both >0.7. The final service quality index system for AI health care chatbots comprises 5 primary indicators and 17 secondary indicators. There were 3 (18%) indicators on assurance, 4 (24%) on reliability, 3 (18%) on human-likeness, 4 (24%) on tangibility, and 3 (18%) on responsiveness. The primary indicators, ranked from highest to lowest weight, were assurance (0.239), reliability (0.237), human-likeness (0.187), tangibility (0.170), and responsiveness (0.167). Conclusions: This study pioneers the development of a service quality index system for AI health care chatbots adapted from the SERVQUAL framework. The results provide a validated tool for evaluating the performance of chatbots and offer valuable insights for health service managers and developers to enhance AI-driven medical consultation services.

In this retrospective cross-sectional study, we assessed sex differences in in-basket messages generated by outpatient workflows among internal medicine specialists as compared to relative value units; we found that female physicians had a greater burden of in-basket work for each unit of paid clinical care.

Date Submitted: Feb 15, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 7, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 6, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Background: Tobacco-related noncommunicable diseases (NCDs) present a major public health challenge in China, requiring population-level management. Chronic obstructive pulmonary disease (COPD) is the most common and prevalent chronic respiratory disease associated with tobacco use. In addition, COPD shares risk factors with other NCDs that frequently co-occur, leading to multimorbidity. This #Study focuses on the early detection and integrated management of COPD and related multimorbidity among high-risk populations. Population medicine, an emerging and evolving concept aimed at maximizing population health and well-being, provides a promising framework for shifting interventions against COPD from an individual patient focus to a population-level approach. Objective: This #Study aims to evaluate the effectiveness of a population medicine–based multimorbidity intervention package among individuals at high risk for COPD. Methods: We are conducting a 2-arm, population-based, stratified cluster #RCT #ClinicalTrial (cRCT). The intervention integrates community screening, chronic disease management, patient education, #Digital follow-up, and team-based care. The trial is being implemented in Xishui County, Guizhou Province, a low-resource county in Southwestern China. Each of the 26 townships in Xishui County was considered a cluster and stratified into large and small townships based on population size. An equal number of residents from each township stratum (large and small) were randomized to undergo the COPD Screening Questionnaire. Individuals identified as being at high risk for COPD were considered #Study participants and were subsequently enrolled in either the intervention or control arm. The target sample size was approximately 2850 individuals. Results: Data collection for the POPMIX-COPD trial began in June 2024. Baseline, 3-month, and 6-month assessments have been completed, and 12-month follow-up assessments are planned to be completed in March 2026. All participants in the intervention arm are being followed for 1 year, with 1 telephone follow-up at month 3 and in-person follow-ups at months 6 and 12. Primary outcomes for each participant include the number of chronic conditions controlled, receipt of lung function testing, and forced expiratory volume in 1 second. In addition, secondary outcomes were health-related quality of life, mental and behavioral health status, health care utilization, knowledge of COPD and asthma, and care cascade indicators for chronic conditions. Conclusions: This cRCT is the first multimorbidity intervention #Study designed within the population medicine framework to target populations at high risk for COPD. It was featured as a case #Study in the report of the Lancet Commission on Investing in Health. The results of the trial are expected to inform the next generation of multimorbidity management and population medicine practices among global health authorities and practitioners. Trial Registration: ClinicalTrials.gov NCT06456996; https://clinicaltrials.gov/ct2/show/NCT06456996

Date Submitted: Feb 15, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 14, 2026. Open Peer Review Period: Feb 17, 2026 - Apr 14, 2026.

Date Submitted: Feb 17, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 17, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 17, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Date Submitted: Feb 17, 2026. Open Peer Review Period: Feb 18, 2026 - Apr 15, 2026.

Background: Social isolation and loneliness have considerable health implications. Research indicates that older men are generally more susceptible to social isolation compared with women, highlighting the need to integrate gender-responsive approaches in the development and implementation of interventions for mitigating social isolation and loneliness in later life. Objective: This study aimed to conduct a review of intervention programs targeting social isolation and loneliness, focusing on gender-specific considerations. Specifically, it aims to examine the gender composition (male-to-female ratio) of participants in intervention programs and identify and analyze intervention strategies that demonstrate gender-sensitive effectiveness. Methods: A scoping review was conducted as per the Joanna Briggs Institute manual for evidence synthesis. A comprehensive literature search, including hand searching, was conducted across 6 English-language databases, PubMed, MEDLINE, Cochrane, CINAHL, ScienceDirect, and Web of Science, for papers and reports published in 2013-2023. The authors, country, subjects, research design, intervention method, results, and mentions of gender for each included document were presented. Results: The study identified 1282 papers and reports, of which 10 were selected for analysis. Only 1 study reported a higher number of male participants compared with female ones; in contrast, all other studies included predominantly female samples. The studies assessed outcomes based on 2 indicators of social isolation, 4 indicators of loneliness, and 29 other indicators. Exercise and workshops proved effective for social isolation and loneliness, while meditation and laughter therapy were effective for loneliness. The intervention with the highest percentage of male participants (264/323, 82%) was a customized meditation program. Conversely, physical activities, social support, and community-based group health classes drew more female participants. In total, 8 studies did not mention gender in the discussion section, and none considered gender-specific issues in formulating research objectives and outcomes. Conclusions: Research on social isolation and loneliness has generally ignored the influence of gender. The review also indicated a gender bias in participant selection, with women markedly overrepresented in study samples. The study found that women tend to prefer interventions emphasizing conversations, shared experiences, and emotional exchange. In contrast, men showed the highest participation in a meditation program focused on self-dialogue, which required minimal interaction. Importantly, interventions aimed at promoting social interaction or participation are unlikely to succeed without consideration of gender-specific issues. Therefore, systematically identifying conditions necessary for effective interventions that target older men is crucial for guiding future research and program development. Trial Registration: Open Science Framework 10.17605/OSF.IO/83JQF; hhttps://osf.io/83jqf/overview

Background: As a critical period in psychosocial development, adolescence is marked by heightened emotion regulation demands as well as increased risk for, and vulnerability to, stress. Objective: This longitudinal #Study investigates how dynamic patterns (ie, mean intensity, variability, instability, inertia, and reactivity to stress) in positive and negative affect relate to, and predict change in, broad domains of adolescent psychosocial well-being (ie, mental health, social well-being, and academic motivation). Using a daily diary procedure to capture adolescents’ daily naturalistic affective experiences, this #Study will provide novel insights into how affective processes predict psychosocial well-being over time beyond traditional, static assessment. Methods: At baseline, adolescents aged 14-17 years from Southwestern Ontario reported on their academic motivation (eg, extrinsic motivation), social well-being (eg, social support and loneliness), and mental health (eg, anxiety syndrome severity) before completing a 35-day #Smartphone #mHealth-based daily diary #Protocol wherein participants reported twice daily in the morning (ie, 7-10 AM) and evening (ie, 8-11 PM) on positive and negative affect, stress, and internalizing symptom severity. Participants then repeat the surveys of academic motivation, social well-being, and mental health 6, 12, and 18 months following baseline assessment to assess change in each domain of psychosocial well-being over time. Results: Adolescents (N=149) were enrolled into this longitudinal #Study between April 2023 and November 2024, such that all participants will complete the scheduled 18 months of longitudinal follow-up assessments by May 2026. Primary #Study analyses will use multilevel modeling, structural equation modeling, multilevel structural equation modeling, and dynamic structural equation modeling to examine how dynamic patterns in positive and negative affect (eg, instability, inertia) concurrently correlate with, and prospectively predict change in, psychopathology and well-being. Conclusions: This #Study #Protocol paper outlines the overarching #Study objectives and methodology to promote transparency and reproducibility. Through the integration of daily diary methodology within a longitudinal design, this #Study aims to clarify the potential implications of dynamic affective processing (eg, affective reactivity to daily stress) for both adolescent psychopathology and well-being beyond clinical syndromes.

Background: The existing intravenous systemic anticancer therapy (SACT) pathway in pharmacies is operationally inefficient. Manual, paper-based workflows render the system prone to human error, and the need for time-consuming manual verification diverts pharmacy staff time. The introduction of an automated workflow solution for the intravenous SACT pathway could optimize treatment timeliness and improve oncological outcomes for patients, aligning with the National Health Service Long Term Plan for improved cancer care. Objective: This observational analysis aimed to assess the change in time, cost, and errors following the implementation of the Becton Dickinson (BD) Cato Pharmacy system in an aseptic unit producing intravenous SACT at Watford General Hospital. Methods: Data on compounding process times were collected manually by pharmacy staff before and after the implementation of the intravenous compounding software (BD Cato). The data were analyzed to estimate annual time savings, opportunity cost savings, and error reduction. Results: The intravenous compounding software produced a time saving of 18 (SD 9) minutes per drug, equating to 1034 hours saved per year (1034/2591, 39.9% reduction). If this time were repurposed to producing more intravenous SACT, Watford General Hospital could increase production by 66% (2298/3482) annually (2298 additional intravenous SACT). This represents an average cost saving of £11.29 (£1=US $1.273) per drug, equating to an annual opportunity cost saving of £39,246. The intravenous compounding software also decreased observed errors by 86% (43/50), a reduction of 43 errors over 2 months (approximately 258 fewer errors annually). Staff also preferred the intravenous compounding software to the manual system. Conclusions: Implementing intravenous compounding software can save time, reduce costs, and lower errors in intravenous SACT preparation. This could improve timely treatment access for patients with cancer.

Date Submitted: Feb 16, 2026. Open Peer Review Period: Feb 17, 2026 - Apr 14, 2026.

Background: As the world’s population ages, the prevalence of chronic low back pain (CLBP) is increasing, placing a substantial burden on individuals and healthcare systems. #Mobile #Health (#mHealth) apps offer a potentially scalable solution to support self-management, but little is known about how, why, for whom, and under what circumstances such tools work in real-world settings. Objective: This study aimed to test and refine three programme theories—developed through a prior realist review—on how #Mobile apps support CLBP self-management. The goal was to understand the key contextual factors and mechanisms that influence when and why a #Digital self-management intervention may succeed or fail. Methods: A realist evaluation was conducted using one-on-one #Telephone interviews with nine participants who had used the Curable #App for three months to self-manage their CLBP. Realist interviews followed a teacher–learner cycle to explore, test, and refine the programme theories. Abductive and retroductive analysis was used to develop context–mechanism–outcome configurations (CMOCs), which were synthesised into refined theories of #Digital self-management in chronic pain. Results: Twenty CMOCs were constructed, supporting three overarching programme theories centred on empowerment, self-management burden, and timing. First, the #App was empowering when it offered credible and accessible knowledge that helped participants understand their pain, build confidence, and reduce reliance on healthcare providers. However, engagement depended on individual beliefs and expectations: those with strong biomedical views struggled to connect with the #App’s psychosocial framing. Second, while the #App could ease the burden of self-management by offering support between appointments, it could also increase burden during flare-ups, when users lacked the capacity to engage. Features such as proactive content delivery and low-demand interfaces were viewed as essential for continued use. Third, timing emerged as a key factor. Early introduction was beneficial for some, but others needed to first accept the chronicity of their condition before they were ready to engage with self-management tools. Trust in the source recommending the #App also influenced engagement. While clinician endorsement was often valued—especially early in the self-management journey—participants who had experienced unmet needs or disillusionment in clinical encounters reported that peer recommendations or non-clinical sources held greater weight. This highlights the importance of aligning recommendations with individuals' evolving relationships with authority and trust. Conclusions: #Mobile apps like Curable can support empowerment and continuity of care in CLBP, but their success depends on personalisation, timing, and relational dynamics. To prevent feelings of abandonment, such tools should be introduced as an adjunct to—rather than a replacement for—ongoing clinical support.

Background: The loss of tooth structure in endodontically treated teeth compromises their structural integrity and increases their vulnerability to fractures. To strengthen these teeth, post and core systems must be used. Glass fiber posts have become more and more common among post materials because of their advantageous mechanical and aesthetic qualities. However, the effectiveness of customized glass fiber posts in enhancing fracture resistance compared to prefabricated ones remains a subject of ongoing debate. Objective: The loss of tooth structure in endodontically treated teeth compromises their structural integrity and increases their vulnerability to fractures. To strengthen these teeth, post and core systems must be used. Glass fiber posts have become more and more common among post materials because of their advantageous mechanical and aesthetic qualities. However, the effectiveness of customized glass fiber posts in enhancing fracture resistance compared to prefabricated ones remains a subject of ongoing debate. Methods: To locate relevant studies published up to 2025, a comprehensive literature search will be conducted through various materials available electronically on websites such as Google Scholar, Web of Science, PubMed, Semantic scholar and Scopus. The selection criteria would be considering in randomized controlled clinical trials that evaluate fracture resistance of customized glass fiber posts in teeth that have had endodontic treatment. The #Research will be screened using predetermined standards for inclusion and exclusion. Quality assessment as well as collection of data will be done strictly in accordance with PRISMA guidelines. To look at the results quantitatively, a meta-analysis will be conducted, if at all possible, by random effect model for heterogenicity. Statistical methods will be used for evaluating the effectiveness of custom glass fiber posts, alternative post materials, and prefabricated posts. Results: By comparing the mean differences in fracture resistance of a tooth treated endodontically using various post systems, the effectiveness of customized glass fiber posts will be assessed. Aspects including general biomechanical performance, failure mechanisms, and stress distribution will all be examined. This #Study will use a random-effects model to estimate the combined effect size measurements and the corresponding 95% confidence intervals. It is anticipated date that the data synthesis for this systematic review will be finished by starting from April 2025 to July 2025. Conclusions: Customized glass fiber posts may show promising in strengthening teeth that have undergone endodontic treatment by lowering the risk of failure and increasing fracture resistance. Even if there is current evidence that they are more effective than prefabricated posts, we need to synthesize quality of evidence. Therefore, this review aims to evaluate the efficacy of fracture resistance of customized glass fiber post in endodontically treated teeth. Clinical Trial: PROSPERO 2025 CRD420250651870; https://www.crd.york.ac.uk/PROSPERO/view/CRD420250651870.

Fat-soluble vitamins (FSVs), including vitamins A, D, E, and K, are essential micronutrients that play critical roles in maintaining human health. Deficiencies or excessive intake of these vitamins can influence clinical decisions regarding nutritional status and the risk of associated diseases. In China, current clinical practice often relies on reference intervals (RIs) derived from Western studies, and no large-scale #Study has comprehensively analyzed all four FSVs in a healthy Chinese adult population. This #Study aims to establish RIs for the four FSVs in healthy Chinese adults, providing clinicians with improved tools for assessing vitamin status and preventing related diseases. This cross-sectional #Study will recruit 100,000 adults aged ≥18 from 20 participating hospitals across China. The data collection process will involve administering a questionnaire and a comprehensive physical examination, including blood sample collection for laboratory testing. FSVs levels in blood samples will be quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rates will be compared using χ² test or Fisher test. Nested ANOVA will be employed to evaluate reference values across subgroups, and RIs will be determined as the central 95% range. The 2.5th and 97.5th percentiles of reference values for each final reference group will be calculated using non-parametric methods to define the lower and upper reference limits, respectively.

Background: Hikikomori is a state of social withdrawal first identified in Japan gaining interest globally. Classically, hikikomori is described as a state of isolation within one’s home, though recent conceptualisations have proposed a continuum of severity. Hikikomori frequently shares symptoms with depression, social anxiety, autism and schizophrenia, as well as internet and gaming disorders. Clinical case studies and cross-sectional studies suggest dysfunctional emotion regulation, familial support and internet behaviours are proposed to contribute to the onset and maintenance of a withdrawn state, though they have not been explored longitudinally. Objective: To investigate affective, behavioural and cognitive correlates of hikikomori symptoms, and how daily mood, social enjoyment, familial support and internet usage may maintain a socially withdrawn state. Methods: A minimum of 84 participants aged between 18-60 will complete self-report measures of hikikomori symptoms, internet addiction, depression, anxiety, autism, and fear of offending others before participating in 14 days of EMA surveys. Surveys will be delivered 5 times per day from 08:00 to 20:00, measuring mood, internet behaviour, familial relationships, social interaction frequency, anticipatory and consummatory enjoyment, sleep quality and physical activity. Participants will repeat the self-report measure of hikikomori symptoms post-monitoring period. Results: Recruitment began in November 2025. Data collection and analysis is scheduled to be completed by summer 2026, with the results also scheduled to be available by the end of summer 2026. Correlation and multiple regression analyses will investigate whether internet addition, social anxiety, expressive suppression, and fear of offending others and daily mood, internet use, social enjoyment and familial support predict hikikomori symptoms. Time-lagged network analyses will explore the temporal dynamics of these relationships, and how these differ in those with high and low levels of hikikomori symptoms. Finally, time-lagged logistic regressions will explore which factors predict future social behaviour. Conclusions: This #Study will be the first to investigate currently proposed mechanisms underlying hikikomori, whilst also exploring the time-varying relationships between affect and social behaviour. The results will provide initial evidence for factors that predict hikikomori symptoms, explore candidate mechanisms underlying hikikomori and identify potential maintenance factors as targets for intervention. Clinical Trial: OSF https://osf.io/bmyn6