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Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% &#x2265;3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Humans

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or &#x2265;2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (&#x2265;160-179 and/or &#x2265;100-109 mmHg), and severe (&#x2265;180 and/or &#x2265;110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or &#x2265;2 blood pressures &#x2265; 140 and/or &#x2265;90 mmHg at &#x2265;20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

Space to grieve and grow: A systematic review of psychosocial interventions for people newly diagnosed with multiple sclerosis.

OBJECTIVE: This systematic review synthesized evidence from intervention studies published over the past 25 years that aimed to improve coping and psychosocial well-being among individuals early in the multiple sclerosis (MS) disease course. The goal was to evaluate intervention characteristics, theoretical foundations, and psychosocial outcomes, and to identify gaps for future research. METHODS: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, CINAHL, PsycINFO, and Web of Science (2000-2025). Eligible studies included quantitative or mixed-methods interventions that addressed coping or psychosocial well-being among adults newly diagnosed with MS. Data extraction and quality assessment were completed independently by multiple reviewers using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Seven studies (n&#x202f;=&#x202f;345) met inclusion criteria, representing cognitive-behavioral therapy, mindfulness, acceptance-based, and nurse- or peer-delivered interventions. The interval between diagnosis and intervention enrollment ranged from 14 days to >4 years, suggesting different phases of adjustment. All interventions produced significant short-term improvements in at least one psychosocial domain (e.g., anxiety, depression, stress, coping, or illness acceptance). However, sustained effects beyond 6-12 months were inconsistent. Common mechanisms across interventions included enhancing self-efficacy, stress management, and adaptive coping. CONCLUSIONS: The available evidence suggests that brief psychosocial interventions for adults in the early years after MS diagnosis are feasible and may provide short-term benefits for selected psychosocial outcomes. However, the evidence base remains limited, heterogeneous, and preliminary. Future studies should more clearly define diagnosis timing, use adequately powered designs and longer follow-up, and examine mechanisms of change.

Humans

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n&#x202f;=&#x202f;2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120&#x202f;Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5&#x202f;mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans

The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p&#xa0;=&#xa0;0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p&#xa0;=&#xa0;0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

Humans

Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p&#x202f;=&#x202f;.041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p&#x202f;=&#x202f;.020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans

Adding Rib Mobilization to Diaphragm Release Techniques in Patients With Non-Specific Neck Pain: Randomized Controlled Trial.

BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45&#xa0;years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40&#xa0;minutes, three times weekly for 8&#xa0;weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8&#xa0;weeks (p&#xa0;=&#xa0;0.001 and f-value&#xa0;=&#xa0;4.15, &#x19e;2&#xa0;=&#xa0;0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p&#xa0;=&#xa0;0.001, f-value&#xa0;=&#xa0;3.16, &#x19e;2&#xa0;=&#xa0;0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.

Humans

Metagenome-scale modeling to assess microbiome metabolic complementarity for precision microbiota transplantation therapies.

Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable and donor-selection strategies remain limited, in part because the role of donor&#x2012;recipient metabolic interactions in shaping the post-FMT community remains poorly understood. Here, we leverage metagenome-scale metabolic modeling to quantify metabolic niche complementarity between donor and recipient microbiomes and predict post-FMT community composition. Using MICOM-derived metabolic models, we show that donor genomes whose metabolic flux profiles are more dissimilar from the recipient community colonize at significantly higher rates in a murine FMT model. In a human IBS trial, the same metric predicted post-FMT community composition via leave-one-out cross-validation and captured known disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to evaluate personalized donor screening, identifying super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition. Together, these results support metabolic niche complementarity as a potential determinant of post-FMT community composition and provide a mechanistic basis for evaluating donor-recipient metabolic compatibility. This framework offers a scalable approach for generating testable hypotheses for personalized donor selection.

Fecal Microbiota Transplantation

Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a&#xa0;meta-analysis.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score &#x2264;10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

Humans

A therapeutic atlas of monogenic inflammatory bowel disease.

BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n&#x2009;=&#x2009;62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I&#xb2; statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R&#xb2;=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans

A smartphone-integrated Pt@Cu-HCF nanozyme-based paper sensor for on-site determination of total antioxidant capacity in marine oils.

Total antioxidant capacity (TAC) serves as a key indicator for evaluating the nutritional quality of foods. In this study, we designed a platinum-embedded copper hexacyanoferrate (denoted as Pt@Cu-HCF) nanozyme that exhibits high oxidase-like activity, efficiently catalyzing the oxidation of chromogenic substrates to generate robust colorimetric signals. Antioxidants quench hydroxyl radicals (&#x2219;OH) produced during the catalytic process, leading to a concentration-dependent suppression of the color signal. Leveraging this mechanism, a smartphone-integrated, colorimetric paper sensor for on-site TAC quantification was developed, using vitamin E as the calibration standard. The sensor was applied to determine TAC in fish oil, algal oil, and krill oil, demonstrating a linear response range of 9.78-312.5&#xa0;&#x3bc;M and a limit of detection (LOD) of 6.41&#xa0;&#x3bc;M. Validation using real-world marine oil samples showed excellent agreement with a commercial assay kit, confirming the reliability and practical applicability of this portable sensor for TAC measurement in complex biological matrices.

Antioxidants

Effect of Music on Pain, Anxiety, and Satisfaction During Intrauterine Device Application: A Randomized Clinical Trial.

This randomized controlled trial aimed to determine the effect of music played during intrauterine device (IUD) insertion on perceived pain, state anxiety, and satisfaction levels. The study was conducted with 70 women who applied to a maternal and child health and family planning center and were randomly assigned to the intervention and control groups using simple randomization. Data were collected using a Demographic Information Form, the State-Trait Anxiety Inventory (STAI-I), and the Visual Analog Scale (VAS), as well as Bluetooth speakers and the musical piece Evgeny Grinko-Valse. Participants in the intervention group listened to music before and during the IUD insertion procedure, whereas the control group received routine care only. Data were analyzed using SPSS version 26 with appropriate descriptive and inferential statistical methods. Women in the music group had significantly lower perceived pain (p&#x2009;<&#x2009;0.001) and state anxiety levels during the procedure (p&#x2009;=&#x2009;0.022), and significantly higher satisfaction levels compared with the control group (p&#x2009;<&#x2009;0.001). In addition, post-procedure state anxiety levels were positively correlated with pain intensity experienced during and after the procedure (r&#x2009;=&#x2009;0.542 and r&#x2009;=&#x2009;0.496, respectively; p&#x2009;<&#x2009;0.001), and negatively correlated with procedural satisfaction (r&#x2009;=&#x2009;-0.652; p&#x2009;<&#x2009;0.001). These findings suggest that listening to music during IUD insertion may help reduce pain and anxiety while potentially enhancing patient satisfaction. Trial Registration: NCT06215183.

Humans

Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10&#x2009;IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5&#x2009;&#xd7;&#x2009;ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

Humans