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Efficacy of transcranial alternating current stimulation for musculoskeletal pain and sleep quality: a systematic review and meta-analysis.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique, emerging as a potential therapeutic option for musculoskeletal pain management. OBJECTIVE: To comprehensively evaluate the efficacy and safety of tACS for alleviating pain and improving sleep quality in adults with musculoskeletal pain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Seven major databases and other sources were searched from inception until April 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. A random-effects model was used to pool standardized mean differences (SMDs). The certainty of evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation framework. RESULTS: Six RCTs involving 232 participants were included. Meta-analysis showed that tACS could significantly reduce pain intensity compared to control (SMD = -0.355, 95% CI: -0.625 to -0.084, p = 0.010, I² = 28.7%). However, no significant improvement was found for sleep quality (SMD = 0.004, 95% CI: -0.310-0.317, p = 0.982, I² = 0.0%). Adverse effects were mild and transient, comparable to sham stimulation. The overall certainty of evidence was rated as low for both pain and sleep quality outcomes. CONCLUSION: Current evidence suggests that tACS may be beneficial for musculoskeletal pain; however, the available evidence remains limited and should be interpreted cautiously. The effect of tACS on sleep quality remains uncertain because of the limited number of available studies. Future well-designed RCTs with standardized outcome measures, condition-specific stimulation protocols, and longer follow-up are required to establish the efficacy and long-term safety of tACS.

Humans

Intervention Without Borders - an Automated Self-Guided AI-Enhanced Psychoeducation Intervention for Dementia Caregivers: Parallel-Group Randomized Waitlist-Controlled Trial.

OBJECTIVE: To examine whether a fully automated, self-guided intervention (PDC30) could improve caregiver well-being over a 1-month waitlist control in an international sample. DESIGN: Randomized waitlist-controlled trial. SETTING: Web-based platform accessible globally. PARTICIPANTS: 441 individuals responded to study promotion on the internet, of whom 274 from 43 countries met the study criteria and were randomized. Eligible participants were adults providing ≥10 care hours weekly to community-dwelling relatives with dementia, scoring ≥5 on Patient Health Questionnaire-9 (PHQ-9), and without recent caregiver intervention. INTERVENTION: Available 24/7, PDC30 is a self-guided, automated intervention consisting of a Guidebook, an AI-powered counseling chatbot, and interactive applications for cognitive-behavioral techniques, relaxation, and caregiver-recipient bonding. MEASUREMENTS: At baseline and follow-ups at 1, 2, and 3 months, depression was assessed by PHQ-9. Secondary outcomes were measured with validated brief versions of anxiety, burden, and positive gains. RESULTS: Intent-to-treat analysis using mixed-effects regression showed treatment x time2 effects on all outcomes except anxiety. At 1-month follow-up, coinciding with exclusive access to PDC30, intervention caregivers showed significant improvements in depression (d = -0.37), burden (d = -0.34), and positive gains (d = 0.42). The differences mostly disappeared after control participants received the intervention, while improvements in both groups were sustained thereafter. Participants reported using the website several times weekly, were generally satisfied with it, and found the chatbot most helpful. CONCLUSIONS: The effects on depression and other outcomes were consistent with those observed for in-person programs, suggesting the viability of well-designed automated intervention. The study demonstrates the feasibility, acceptability, and potential global health impact of PDC30.

Humans

Mixed Methods Research on Family Caregiving for Stroke Survivors: A Methodological Systematic Review.

AIM: To examine how mixed methods research has been applied in studies of family caregiving for stroke survivors, focusing on key methodological components (rationale, design types, integration strategies, and use of joint displays). DESIGN: Methodological systematic review. METHODS: A systematic search of five databases yielded 17 studies. The extraction focused on mixed methods features (rationale, design, integration, joint displays), and quality was appraised using the Mixed Methods Appraisal Tool. DATA SOURCES: PubMed, CINAHL, Scopus, Web of Science, and PsycINFO were searched for relevant studies published from 2010 to 2025. RESULTS: The included studies addressed topics such as caregiver burden, coping, resilience, and intervention outcomes. Convergent and explanatory sequential designs predominated. Complementarity was the most frequent rationale for mixing methods. Integration occurred mainly through merging, with fewer instances of connecting or building. Three studies included joint displays to integrate the results. CONCLUSION: Mixed methods research is increasingly applied in family caregiving. To advance the field, researchers should strengthen integration during analysis and results and improve transparency in reporting key design features. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Strengthening methodological rigour in mixed methods studies on stroke caregiving will improve the evidence base for nursing practice. Intentional and meaningful integration of qualitative and quantitative evidence can better inform effective interventions and support programs, ultimately enhancing care for stroke survivors and their families. IMPACT: This review evaluates how mixed methods research is applied in family caregiving studies. It identifies significant methodological gaps, including unclear reporting of design and limited use of advanced integration techniques. The recommendations provide practical guidance for researchers to improve reporting and integration, yielding richer evidence to inform interventions and policies that support family caregivers. REPORTING METHOD: The review followed the PRISMA 2021 guidelines for transparent reporting of systematic reviews. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Humans

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA

Efficacy and safety of endoscopic ultrasound-guided choledochoduodenostomy compared with endoscopic ultrasound-guided gallbladder drainage for palliation of malignant distal biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: When ERCP is not feasible or fails in the palliation of malignant distal biliary obstruction (MDBO), EUS-guided choledochoduodenostomy (EUS-CDS) and EUS-guided gallbladder drainage (EUS-GBD) are viable alternatives. We conducted a systematic review and meta-analysis comparing the safety and efficacy of the 2 techniques for the palliation of MDBO. METHODS: Multiple databases were searched through November 2025 for studies that reported outcomes of EUS-CDS and EUS-GDB in patients with MDBO. A meta-analysis was performed to determine pooled proportions and relative risk (RR) with 95% CIs. We compared the rates of technical and clinical success, overall adverse events (AEs), and lumen-apposing metal stent dysfunction. A random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I2 (%) statistics. RESULTS: Five studies (352 patients; EUS-CDS: 193 and EUS-GBD: 159) were included. Technical success was 93.3% (95% CI, 70.6-98.8) for EUS-CDS and 95.9% (95% CI, 90.0-98.4) for EUS-GBD (RR, 1.02; 95% CI, 0.94-1.10; P = .6). Clinical success was 90.1% (95% CI, 84.7-93.7) versus 86.6% (95% CI, 80.3-91.0) (RR, 0.97; 95% CI, 0.90-1.05; P = .4). There were no significant differences in overall AEs (19.7% vs 17.6%; RR, 0.93; 95% CI, 0.58-1.48; P = .8), severe AEs (11.0% vs 8.3%; RR, 0.69; 95% CI, 0.33-1.44; P = .3), or stent dysfunction (15.0% vs 14.5%; RR, 0.95; 95% CI, 0.35-2.58; P = .9). CONCLUSIONS: EUS-GBD appears comparable to EUS-CDS in terms of technical and clinical success, AEs, and stent dysfunction. Further prospective studies are warranted to corroborate our findings.

Humans

Effectiveness of high-power laser use in the removal of esthetic restorations: a systematic review.

This systematic review aimed to evaluate the effectiveness of high-power lasers in the removal of esthetic restorations compared with conventional methods. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (registration number: CRD420251055736). A comprehensive electronic search was performed in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. Study selection, data extraction, and methodological quality assessment were independently performed by four reviewers using QUIN tool for in vitro studies. A total of 2.384 records were identified, of which 19 in vitro studies conducted on extracted human permanent teeth met the eligibility criteria and were included in the qualitative synthesis. The included studies evaluated different high-power laser systems, predominantly Er: YAG and Er, Cr: YSGG lasers, as well as CO₂ lasers. Five studies were classified as high quality, whereas the remaining fourteen studies were classified as moderate quality. Available laboratory evidence suggests that laser-assisted techniques may represent a potential alternative approach for removing esthetic restorations, with advantages including conservative tissue removal, reduced damage to underlying tooth structures, and intrapulpal temperature increases within acceptable limits. The Er: YAG laser was the most frequently investigated system, with power settings ranging from 1.5 to 5.9 W, showing particularly favorable laboratorial performance in the removal of lithium disilicate restorations, especially in thinner substrates. Within the limitations of the available evidence, high-power lasers appear to be a promising and minimally invasive alternative to conventional methods for the removal of esthetic restorations. However, the predominance of in vitro studies highlights the need for well-designed clinical trials to confirm these findings and support their clinical application.

Humans

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p&#x2009;<&#x2009;0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had &#x2264;US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans

Meta-PseU: A meta-classifier for robust prediction of RNA pseudouridine modification sites from long sequences.

BACKGROUND AND OBJECTIVES: Pseudouridine (&#x3a8;) represents one of the most abundant and conserved RNA modifications. &#x3a8; provides an additional hydrogen-bond donor that enhances RNA structural stability and modulates translation. It participates in diverse biological processes, including RNA-protein interactions, splicing, translational control, and stress responses. Aberrant pseudouridylation is implicated in cancer, neurodegenerative disorders, and autoimmune diseases. Despite its biological importance, experimental identification of &#x3a8; sites remains time-consuming and costly, limiting the feasibility of transcriptome-wide profiling. Computational approaches have therefore become essential complements to experimental techniques. However, state-of-the-art machine-learning and deep-learning predictors often suffer from limited generalizability due to small training datasets. To overcome these issues, we aim at constructing new long-sequence datasets and developing a novel &#x3a8; site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA &#x3a8;-site prediction. The &#x3a8; modification sites in RMBase 3.0 were mapped to the reference genomes across three species of human, mouse, and yeast, and the RNA sequences with a length of 201 were generated by extending the upstream and downstream from the mapped, central sites. To eliminate sequence redundancy, the sequences were clustered using CD-HIT with a 70% sequence identity threshold. We developed Meta-PseU, a logistic regression-based meta-classifier that considered 118 machine learning and deep learning classifiers. The datasets and programs are freely accessible at https://github.com/kuratahiroyuki/MetaPseU. RESULTS: By optimizing model configuration, we proposed the Meta-PseU model stacking 32 machine learning and deep learning classifiers out of 118 classifiers. Meta-PseU substantially improved model generalizability, overcoming a key limitation of existing approaches. It greatly outperformed state-of-the-art predictors and achieved increasing accuracy with increasing sequence length. CONCLUSIONS: Long-sequence datasets were newly constructed as benchmarks for RNA &#x3a8;-site prediction. Meta-PseU offers a new framework for robust &#x3a8;-site identification by using long sequences.

Pseudouridine

Copper-Containing Surface Engineering for Soft-Tissue Biomedical Devices: Structure-Function Relationships and Ion Release-Driven Biological Performance, A Systematic Review.

Copper and copper-based materials have gained increasing attention for the functional modification of implantable medical devices intended for prolonged soft-tissue contact, including vascular stents, catheters, and intrauterine devices. Owing to their broad-spectrum antimicrobial activity, redox reactivity, and involvement in angiogenesis and cellular signaling, copper-based systems offer significant potential for multifunctional surface engineering. However, achieving a balance between antibacterial efficacy, corrosion behavior, controlled ion release, and cytocompatibility remains a critical challenge. This PRISMA-compliant systematic review analyzes copper-containing materials and surface modification strategies for soft-tissue biomedical applications. A structured search of Scopus, Web of Science, and PubMed (2015-2025) identified 65 eligible studies. The review encompasses bulk copper-containing alloys, electrochemical and chemical surface modification techniques, physical vapor deposition approaches, and advanced hybrid systems integrating copper with polymers, hydrogels, or metal-phenolic networks. Across the reviewed literature, antibacterial performance was strongly dependent on copper concentration, microstructural distribution, and spatiotemporal ion release profiles. Moderate, well-controlled copper incorporation frequently improved antibacterial efficacy while maintaining acceptable hemocompatibility and cytocompatibility, particularly in vascular and blood-contacting devices. In contrast, excessive copper loading often accelerated corrosion and induced adverse cellular responses. Emerging multifunctional architectures demonstrated improved regulation of biological interactions, enabling simultaneous antibacterial, antithrombotic, and proendothelial effects. Overall, copper-based surface technologies represent a versatile platform for soft-tissue implant modification. Future translational progress will require precise control of copper release kinetics and comprehensive long-term in vivo validation to ensure safety and sustained therapeutic performance. From the authors' perspective, the most promising future direction involves multifunctional copper-based hybrid coatings capable of dynamically regulating ion release, host tissue integration, and antibacterial performance simultaneously. Strategies integrating hierarchical architectures, stimulus-responsive release systems, and clinically scalable fabrication methods are expected to play a key role in translating copper-containing surfaces from experimental concepts toward commercially viable soft-tissue biomedical devices.

Copper

A framework for delivering real-time, instrument-relative navigation in transoral robotic surgery.

Transoral robotic surgery (TORS) is a minimally invasive, inside-out technique that, compared with traditional open approaches, provides fewer post-operative complications, shorter hospital stays, and improved survival for early-stage head and neck cancer. However, TORS is limited by its steep learning curve and poor visualization of deep tumor margins. This randomized crossover study evaluated a surgical navigation system's potential to enhance accuracy and user experience with real-time, instrument-relative feedback. Seven Teflon beads (d&#x2009;=&#x2009;2.381&#xa0;mm) were embedded at the tongue base of a porcine pharynx-and-larynx model. Tongue blade compression and retraction were applied to the model to mimic intraoperative tissue deformation, reproducing the anatomical shifts that occur relative to preoperative imaging. Eight participants used the da Vinci Surgical system to localize the beads by placing pins under two conditions: (a) preoperative computed tomography with no navigation; (b) model-based visual navigation with quantitative instrument-to-target metrics. Surgical accuracy was determined by calculating the target localization error (TLE, pin-to-bead Euclidean distance) and the angular error (AE, pin axis trajectory to bead). Accounting for training level and bead depth, surgical navigation reduced TLE by 5.44&#xa0;mm (95% CI, 4.02-6.86&#xa0;mm; p&#x2009;=&#x2009;2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p&#x2009;=&#x2009;5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p&#x2009;=&#x2009;0.26) or cognitive workload via the NASA-Task Load Index (p&#x2009;=&#x2009;0.22) were not significantly affected. The navigation system demonstrated translational promise, offering improved target localization accuracy and more consistent performance across experience levels, two critical determinants of surgical quality in TORS.

Robotic Surgical Procedures

Comparison of ultrasound-guided two-point block of the rhomboid intercostal vs. thoracic paravertebral for postoperative analgesia in patients undergoing three-port thoracoscopic surgery: a prospective, randomized, non-inferiority study.

BACKGROUND: The anesthetic characteristics of ultrasound-guided two-point rhomboid intercostal block (RIB) have not been fully established. This study compared the analgesic efficacy of ultrasound-guided two-point RIB with that of two-point thoracic paravertebral block (TPVB) for postoperative pain control and recovery in patients undergoing three-port thoracoscopic surgery. METHODS: Seventy patients aged 18-80&#x2009;years scheduled for three-port thoracoscopic pulmonary resection were block-randomized in a 1:1 ratio to receive either TPVB or RIB. Both techniques were performed using 10&#x2009;mL of 0.5% ropivacaine at each injection site. The primary outcome was the numerical rating scale (NRS) pain score at rest 24&#x2009;h after surgery, with a predefined non-inferiority margin of &#x394;&#x2009;=&#x2009;1. Secondary outcomes included NRS at rest and during coughing at 0.5, 2, 4, 12, 18, 24, and 48&#x2009;h postoperatively, as well as the 24h postoperative Quality of Recovery-40 (QoR-40) score. RESULTS: The final analysis included 34 patients in the TPVB group and 34 in the RIB group. The mean difference in resting NRS scores at 24&#x2009;h between the two groups was 0.088 (95% CI, -0.377 to 0.553), confirming the non-inferiority of RIB. However, the need for rescue analgesia was numerically greater in the RIB group than in the TPVB group (p&#x2009;=&#x2009;0.045). The 24-h postoperative QoR-40 scores and cumulative sufentanil consumption within 48&#x2009;h after surgery were comparable between the groups (both p&#x2009;>&#x2009;0.05). CONCLUSION: Ultrasound-guided two-point RIB provided postoperative analgesia that was non-inferior to TPVB in patients undergoing three-port thoracoscopic surgery.

Adolescent

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n&#x2009;=&#x2009;211) were randomised to Guided Narrative Technique-Writing (GNT-W, n&#x2009;=&#x2009;100) or Expressive Writing (EW, n&#x2009;=&#x2009;111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b&#x2009;=&#x2009;-0.43, p&#x2009;=&#x2009;.023, d&#x2009;=&#x2009;-0.43; EW: b&#x2009;=&#x2009;-0.60, p&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;-0.58), with no significant between-group difference (group &#xd7; time: b&#x2009;=&#x2009;0.18, p&#x2009;=&#x2009;.48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans

ADAM10's combined influence on the diagnostic usefulness of IL 22, IL 10, IL-17&#xa0;A, and IL-17D in autism spectrum disorders: Predicted role on gut leakiness as co-morbidity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing global prevalence but a lack of reliable diagnostic biomarkers. Emerging evidence suggests that immune dysregulation, gut-brain axis dysfunction, and increased intestinal permeability play key roles in ASD pathophysiology. This study investigated the combined diagnostic value of ADAM10 and cytokines (IL-10, IL-22, IL-17&#xa0;A, and IL-17D). Multivariable logistic regression produces an improved ROC curve that improves diagnostic accuracy over individual markers by combining numerous predictors into a single risk score (linear predictor). The technique, which frequently raises individual marker AUCs, entails modelling a binary result, calculating the probability, and visualizing ROC based on the projected probabilities. In this case-control study, plasma levels of ADAM10, IL-10, IL-22, IL-17&#xa0;A, and IL-17D were measured in 37 male children with ASD and 37 age-matched controls. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curve analyses, including combined ROC models, were performed. ADAM10, IL-22, and IL-17&#xa0;A levels were significantly reduced in children with ASD compared to controls, whereas IL-10 and IL-17D showed no significant differences. ADAM10, IL-17&#xa0;A, and IL-22 demonstrated good diagnostic performance, with AUC values of 0.886, 0.855, and 0.812, respectively. In contrast, IL-10 and IL-17D showed poor discriminatory ability, with AUC values of 0.524 and 0.599, respectively. Combined ROC analysis markedly improved diagnostic accuracy, with all panels including ADAM10 achieving AUC values above 0.90, and some reaching as high as 0.988, with high sensitivity and specificity. The combination of ADAM10 with selected cytokines significantly enhances diagnostic performance compared to individual markers, supporting a link between immune dysregulation, barrier dysfunction, and gut permeability in ASD.

Humans

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 &#xb1; 12.7 min) than the C group (29.9 &#xb1; 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% &#xb1; 1.39% vs. 30.0% &#xb1; 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 &#xb1; 25.3 vs. 63.0 &#xb1; 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 &#xb1; 9.3 vs. 21.5 &#xb1; 12.5, p < 0.01), days of antibiotic use (15.5 &#xb1; 8.7 vs. 18.7 &#xb1; 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

Humans

Minimally invasive versus open surgery for gallbladder cancer: A systematic review and meta-analysis.

INTRODUCTION: Minimally invasive surgery (MIS) is increasingly being used in gallbladder cancer (GBC) for radical tumour extirpation. However, there are conflicting results on the morbidity outcomes following MIS. The aim of this meta-analysis was to compare the post-operative morbidity and mortality in patients undergoing radical surgery for GBC between MIS and open surgery. MATERIAL AND METHODS: Studies comparing MIS (laparoscopic, robotic or both techniques) to open surgery were included. The databases of MEDLINE, Cochrane and EMBASE were searched from 2001 till March 2025. The primary end point was post-operative morbidity and mortality. The secondary end points were hospital stay, blood loss, operative time and R1 resection rates. Random effect models were used for analysis. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Thirty-two studies (laparoscopic [n&#x202f;=&#x202f;19], robotic [n&#x202f;=&#x202f;6] or both [n&#x202f;=&#x202f;7]) involving 8568 (MIS&#x202f;=&#x202f;3287 and open&#x202f;=&#x202f;5281) patients were included. For overall and major morbidity (Clavian-Dindo >/&#x202f;=&#x202f;III), the odds ratio (OR) of 0.60 (95% CI: 0.46-0.78) and 0.72 (95% CI: 0.52-1.0) respectively was obtained, favouring the MIS approach. Similarly, MIS showed lower odds for mortality [OR:0.62 (95% CI: 0.40-0.95)] compared to open surgery. MIS was associated with shorter hospital stay (less by mean of 3 days) and lesser blood loss (less by mean of 115&#x202f;ml) but longer operative time (higher by mean of 5.8&#x202f;min) and higher R1 resection rates (OR: 1.34; 95% CI: 1.05-1.71). Oncological outcomes, however, were comparable. The certainty of evidence was very low to low across the studies. CONCLUSION: MIS for GBC was associated with relatively lower post operative morbidity and mortality with similar oncological outcomes but with a small but heightened risk of margin positive (R1) resection, especially in primary GBC. The certainty of evidence was very low to low across the included studies. Future prospective studies are needed to overcome the clinical heterogeneity and possible selection bias.

Humans

[Effect of oblique needling after equal division and positioning of anatomic points on acute sacroiliac joint injury assessed with infrared thermography].

OBJECTIVE: To evaluate the clinical therapeutic effect of oblique needling after equal division and positioning of anatomic points on acute sacroiliac joint injury assessed with infrared thermography. METHODS: A total of 150 patients with acute sacroiliac joint injury were randomly divided into an oblique needling group, a perpendicular needling group, and an acupressure+tuina group, with 50 cases in each group. After equal division and positioning of anatomic points at sacroiliac joints, the oblique needling, perpendicular needling and acupressure+tuina techniques of acupuncture were operated in three groups, respectively. The treatment was administered once daily, 5 sessions per week; 10 sessions constituted one treatment course, with a total of one course required in the trial. Before and after treatment, the scores of Japanese Orthopaedic Association (JOA), visual analogue scale (VAS) of pain, and World Health Organization quality of life-BREF (WHO QOL-BREF), as well as the average temperature of the lumbosacral region were observed in each group. Additionally, the correlation between the average lumbosacral temperature and efficacy indicators was explored. RESULTS: After treatment, the scores of JOA, WHO QOL-BREF in the oblique needling group were higher (P<0.01, P<0.001), and the VAS score was lower (P<0.01, P<0.001) than those in the perpendicular needling group and the acupressure+tuina group; and the average temperature of the affected lumbosacral region in the oblique needling group was lower compared with that in the other two groups (P<0.001). After treatment, the average lumbosacral temperature of the affected side showed a negative correlation with the JOA score in each group (r=-0.645, -0.482, -0.809, P<0.001). CONCLUSION: Following equal division and positioning of anatomic points, the therapeutic effect of acupuncture with oblique needling is superior to the perpendicular needling and acupressure+tuina on acute sacroiliac joint injury. The average temperature of the affected lumbosacral region is correlated with the severity of lumbosacral dysfunction after treatment.

Humans