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Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

Humans

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of &#x2264;8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score &#x2264;4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans

Men's experiences of multiple long-term conditions and/or disability in the UK Game of Stones weight management trial: a mixed-methods evaluation.

OBJECTIVES: To explore experiences, health outcomes and retention of men with multiple long-term conditions (MLTCs) and/or disability within the Game of Stones weight management randomised controlled trial (RCT). DESIGN: Mixed-methods process evaluation within an RCT where secondary outcomes included the Weight Self-Stigma Questionnaire, EuroQol 5-Dimension 5-Level (EQ-5D-5L), EQ-5D-5L anxiety and depression subscale, Patient Health Questionnaire-4 and retention. Semistructured interviews were conducted at 12 months and analysed using the framework method. SETTING: Conducted across three UK trial centres: Belfast, Bristol and Glasgow. PARTICIPANTS: 585 men with obesity (mean (SD) age, 50.7 (13.3) years) were randomised to one of three groups: behavioural text messages with financial incentives, texts alone or waiting-list control. Interviews were conducted with 54 participants from the two intervention groups. RESULTS: 235 (40%) participants lived with MLTCs, 181 (31%) had a single condition, 167 (29%) had no conditions and 165 (29%) had a disability. Of those with MLTCs, 99 were disabled and 93 were living in deprived areas. Participants with MLTCs and/or disability were older, fewer had a degree-level qualification and fewer were in full-time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%) and lower for men with diabetes (65%). Self-reported weight stigma, well-being and quality-of-life scores improved or stayed the same for men living with MLTCs in the intervention groups; however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, were demotivating for making changes to reach weight loss targets. CONCLUSIONS: Men living with MLTCs and/or disability varied from very successful weight loss and improved health to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes. TRIAL REGISTRATION NUMBER: isrctn.org Identifier: ISRCTN91974895.

Humans

Spatial proximity or vector orientation? Re-evaluating ECG interpretation in anterior myocardial infarction using cardiac magnetic resonance.

BACKGROUND: The electrocardiogram (ECG) is widely used to infer infarct location and extent in anterior myocardial infarction (MI), based on either anatomical lead proximity or vectorial orientation of ST-segment deviation. However, the validity of these approaches against direct imaging of myocardial injury remains uncertain. METHODS: In this prospective study, 105 patients with anterior MI underwent cardiac magnetic resonance (CMR) imaging 3-7&#xa0;days after presentation. Admission ECGs were analyzed using (1) conventional ECG localization categories, and (2) simplified frontal and horizontal ST-axis orientation. CMR-defined injury distribution was assessed using late gadolinium enhancement and myocardial edema imaging. RESULTS: Conventional ECG localization categories demonstrated no significant association with CMR-defined infarct distribution (P&#xa0;=&#xa0;0.24), with poor agreement (&#x3ba;&#xa0;=&#xa0;0.122) and substantial overlap across categories. Simplified ST-axis orientation showed modest and inconsistent associations with infarct location and did not meaningfully explain infarct size. In contrast, global ST-segment burden was associated with CMR-defined infarct size (&#x3a3;STE: standardized &#x3b2;&#xa0;=&#xa0;0.307, P&#xa0;=&#xa0;0.002; lead count: standardized &#x3b2;&#xa0;=&#xa0;0.267, P&#xa0;=&#xa0;0.007). CONCLUSIONS: In this selected cohort of reperfused LAD-related anterior STEMI patients undergoing early CMR, conventional ECG localization categories and simplified ST-axis orientation showed poor or inconsistent correspondence with CMR-defined infarct distribution, whereas global ST-segment burden showed a modest association with infarct size. These findings suggest that, in this cohort, the ECG may be better suited to reflect the extent of myocardial injury rather than its precise anatomical location.

Humans

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans

Genomic and food-safety evaluation of Staphylococcus chromogenes in Chinese dairy milk.

Non-aureus staphylococci and mammaliicocci (NASM) cause mastitis and may contaminate milk and dairy products. Milk samples (n&#xa0;=&#xa0;1916) from cows with subclinical or clinical mastitis (SCM and CM, respectively) were collected from 28 large-scale (> 500 lactating cows) Chinese dairy farms. Overall, 999 NASM isolates representing 19 species were identified by MALDI-TOF MS and cpn60 sequencing, with Staphylococcuschromogenes, Mammaliicoccus sciuri and Staphylococcus haemolyticus being most prevalent. Antimicrobial resistance (AMR) was determined with disc diffusion; non-susceptible to penicillin was most common (SCM, 30% and CM, 29%) whereas cefoxitin non-susceptible NASM accounted for 8-10% of isolates; among these, 12.5% carried mecA but none carried mecC. Galleria mellonella was used to assess virulence of 78 strains of S. chromogenes, a dominant species; subsequently, 32 strains, representing higher- and lower-virulence in the Galleria model, were selected for whole-genome sequencing and comparative genomics. S. chromogenes isolates from CM had higher virulence (p&#xa0;<&#xa0;0.05) than those from SCM. The 32 genomes comprised 20 sequence types, indicating high genetic diversity. No robust genomic marker of Galleria virulence phenotype was identified in this selected WGS subset. Acquired resistance genes (n&#xa0;=&#xa0;5) were detected, including a first report of fusC in S. chromogenes; the fusC-positive isolate had an elevated fusidic acid MIC (8&#xa0;mg/L). Although S. chromogenes persisted in milk at 4&#xa0;&#xb0;C, pasteurization (64&#xa0;&#xb0;C for 30&#xa0;min) reduced viable counts to below detection. This study provided new insights into the prevalence, AMR, genomic diversity, and dairy-chain relevance of milk-derived NASM, particularly S. chromogenes. However, the genomic findings were based on an intentionally selected WGS subset and should be interpreted as hypothesis-generating rather than population-representative.

Animals

A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.

BACKGROUND: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization. METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8&#xa0;weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel &#x3c7;2 (CMH-&#x3c7;2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants. FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7&#xa0;days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%). INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.

Humans

Prognostic value of the lactate-to-albumin ratio in adult sepsis: An updated systematic review of prognostic evidence.

BACKGROUND: The lactate-to-albumin ratio (LAR) has emerged as a potential prognostic biomarker in sepsis. This systematic review evaluated the prognostic value of LAR for mortality in adults with sepsis or septic shock. METHODS: PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library were searched from inception through March 2026. Studies evaluating mortality-related prognostic performance of LAR in adults with sepsis or septic shock were included. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool. Adjusted odds ratios (ORs) and hazard ratios (HRs) were evaluated separately because of methodological heterogeneity. Discrimination was assessed using study-specific area under the curve (AUC), sensitivity, specificity, and LAR thresholds. RESULTS: Fourteen primary studies were included. Higher LAR was consistently associated with increased mortality across emergency department and intensive care populations. AUC values generally ranged from approximately 0.65 to 0.87, although one smaller cohort reported an AUC of 0.976. Several multivariable analyses demonstrated associations between higher LAR and mortality after adjustment for clinical covariates. Adjusted ORs and HRs were not pooled because of differences in LAR scaling, thresholds, mortality endpoints, and adjustment strategies. Considerable variability was observed in reported cut-offs and diagnostic performance. CONCLUSIONS: Higher LAR is associated with mortality in adult sepsis and may provide complementary prognostic information. However, clinical and methodological heterogeneity precludes a universal cut-off or single pooled adjusted effect. Standardized prospective multicenter studies are required before routine clinical implementation.

Humans

Effectiveness of different anaesthetic techniques, agents and adjunctive interventions in handling pain during dental treatment of MIH-affected teeth: a systematic review.

BACKGROUND: Molar incisor hypomineralisation (MIH) is frequently associated with hypersensitivity, dental anxiety and reduced efficacy of local anaesthesia, complicating pain control during dental treatment in children. AIM: To evaluate, based exclusively on randomised controlled trials (RCTs), the effectiveness of different local anaesthetic techniques, agents and adjunctive interventions in reducing pain during dental treatment of MIH-affected teeth in children. METHODS: A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420251150485). MEDLINE, Cochrane Central, ScienceDirect, SCOPUS, EBSCO, and LILACS were searched up to September 2025. Eligible studies were RCTs involving children and adolescents (6 - 18&#xa0;years-of-age) with MIH, assessing pain outcomes during dental procedures. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: Eight RCTs were included. Low-certainty evidence suggested that intraosseous anaesthesia and 4% articaine may reduce intra-operative pain compared with conventional techniques or 2% lidocaine. Adjunctive cryotherapy and pre-emptive ibuprofen showed potential benefits, but evidence was of very low certainty and limited to single trials. Findings for photobiomodulation were inconsistent across studies. Most trials were judged to be at high risk of bias, primarily due to lack of blinding and reliance on subjective pain outcomes. CONCLUSION: Current evidence supporting specific pain management strategies for MIH-affected teeth is limited and of low certainty. Whilst 4% articaine and intraosseous anaesthesia appear promising, well-designed, adequately powered RCTs with standardised pain outcomes are required to inform robust clinical recommendations.

Local anaesthesia

Molecular mechanisms underlying umami taste perception: A DIA-based proteomic analysis of Agrocybe aegerita peptides.

The mechanisms underlying the modulation of the salivary perception of umami peptides remain poorly understood. Herein, three umami peptides (DDL, DEL, and ENG) obtained from Agrocybe aegerita were used to investigate the regulatory role of saliva in umami taste perception via a combined approach involving sensory evaluation and proteomics analysis based on 4D-DIA technology. The results revealed that umami intensity peaked at 10&#xa0;s after ingestion and was accompanied by a significant increase in saliva secretion (p&#xa0;<&#xa0;0.05). Further proteomics analysis revealed that lactotransferrin and proline-rich proteins are closely associated with the sensory perception of umami peptides. Differentially expressed proteins were mainly enriched in pathways related to saliva secretion and proteasome function. This study provides new insights from the perspectives of salivary proteomics and dynamic salivary secretion, contributing to a deeper understanding of the mechanisms by which saliva regulates umami perception.

Humans

The co-existence of Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome: A systematic review of the literature.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3&#xa0;years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Humans

Post-trial 12-month follow-up of TRACE (targeted research on addictive and compulsive eating) randomised controlled trial participants: A brief report.

Few treatment interventions for addictive eating have evaluated long-term effectiveness. This post-trial follow-up study evaluates secondary changes in addictive eating symptoms and quality of life at 12-months in a sample of individuals who participated in the TRACE (Targeted Research for Addictive and Compulsive Eating) RCT. Thirty-three adults out of possible 144 (82% female), median age 53 years, randomised to either the active intervention (five telehealth sessions delivered over 3-months), passive intervention (self-guided workbook) or control group completed an online post-trial survey. Pre- and immediate post-intervention (3-months) outcomes were compared to 12-months post-trial outcomes. Positive effects reported in the short term showed a rebound effect at post-trial follow-up in &#x223c;50% of participants. The findings suggest that longer term support is needed to maintain changes in addictive eating behaviours and improve quality of life. Future research is needed to identify optimal intervention durations and support options for sustained change. Australian New Zealand Clinical Trials Registry (ACTRN12621001079831).

Humans

Extender-dependent effects of reduced glutathione on post-thaw boar sperm quality: A systematic review and meta-analysis.

Supplementation of reduced glutathione (GSH) in freezing media has been proposed to improve post-thaw boar sperm quality, although reported findings remain inconsistent. This study aimed to quantitatively evaluate the effects of reduced glutathione on post-thaw sperm quality through a systematic review and meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scopus, PubMed, CAB Direct, EBSCOhost, and Google Scholar were systematically searched. Based on predefined inclusion and exclusion criteria, 15 in vitro studies comprising 19 experiments were included. Four outcomes were analyzed: total motility, progressive motility, viability, and acrosome integrity. Standardized mean differences (SMD) were calculated using random-effects models. Heterogeneity was assessed using Cochran's Q test, and the I2 statistic. Publication bias was evaluated using funnel plots, Egger's test, and trim-and-fill analysis, while sensitivity analyses were performed using Baujat plots and leave-one-out analysis. Reduced glutathione was positively associated with total motility (SMD = 0.74; 95% CI: 0.42-1.05; P<0.001), progressive motility (SMD = 0.90; 95% CI: 0.21-1.58; P=0.014), viability (SMD = 0.67; 95% CI: 0.11-1.23; P=0.022), and acrosome integrity (SMD = 0.72; 95% CI: 0.32-1.12; P=0.002). Low to high heterogeneity was observed across outcomes, indicating variability in the estimated effects across studies. Significant subgroup differences were identified according to GSH concentration, freezing media, and thawing media. Overall, the available evidence suggests a possible positive association between GSH supplementation and several post-thaw sperm quality parameters, although these subgroup findings are exploratory and require confirmation in well-standardized experimental studies.

Animals

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans

Pre-treatment polyfunctionality percentage (PFA) of CD8+ T cells is associated with development of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer survival, but immune-related adverse events (irAEs) occur frequently and can have devastating consequences. There are no validated methods to evaluate risk of irAEs prior to initiation of ICIs. MATERIALS AND METHODS: We conducted a pilot study evaluating the ability of blood-based, single-cell secretomic analysis to characterize irAEs. A total of 10 patients with thoracic malignancies who were scheduled to receive ICIs were enrolled. Each patient had a pre-ICI blood sample drawn as well as a sample at the time of irAE development or 12 weeks after ICI initiation, whichever came first. Utilizing IsoPlexis's IsoLight system, polyfunctionality percentages (PFAs) and strength indices (PSIs) were analyzed for CD4+ and CD8+ T cells. RESULTS: Five patients developed irAEs and 5 patients did not develop irAEs. Pre- and post-ICI CD8+ T cell PFA was significantly elevated in patients who developed irAEs compared with those who did not (p = 0.017 and p = 0.014, respectively). CONCLUSIONS: In this pilot study, pre-ICI CD8+ T cell PFA was associated with development of irAEs. While this is a pilot study, this is a first step toward developing a blood-based, streamlined assay to assess risk of irAEs prior to initiation of ICIs. Validation in larger cohorts is warranted.

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

Treating neurogenic detrusor overactivity in order to manage autonomic dysreflexia - A systematic review.

INTRODUCTION: Autonomic dysreflexia (AD) is a severe and potentially life-threatening complication of a spinal cord injury (SCI), particularly in patients with lesions at or above the sixth thoracic level. Neurogenic detrusor overactivity (NDO) is one of the main triggering factors. The impact of NDO treatment on AD remains insufficiently clarified. METHODS: We conducted a systematic review of the literature in PubMed and Cochrane Database between January 1990 and May 2025. Eligible studies included patients with SCI and AD undergoing treatment for NDO, including antimuscarinics, botulinum toxin (BTX) or augmentation cystoplasty. The primary outcome was the assessment of systolic blood pressure (SBP) parameters in patients undergoing cystomanometry. RESULTS: Of the thirteen eligible studies, only five were included. No study evaluated augmentation cystoplasty. One study (12 patients) evaluating fesoterodine and four studies (95 patients) evaluating BTX injection demonstrated improved urodynamic parameters and a decrease in severity of AD during urodynamic studies and in daily life. Improvements in AD-HR-QoL and I-QoL scores were also demonstrated. DISCUSSION: Controlling NDO with fesoterodine or BTX injection reduces the prevalence and severity of AD, likely by limiting abnormal C-fiber recruitment and reducing neurogenic inflammation. BTX additionally modulates TRPV1-expressing afferents, which further reduces AD risk. Although hypertensive peaks improve, submaximal parameters remain unchanged, highlighting the need for additional complementary strategies. CONCLUSION: The use of BTX and fesoterodine for NDO treatment effectively reduces AD episodes in patients with SCI. Further long-term studies are needed to confirm the cardiovascular benefits and inform future therapeutic strategies.

Humans