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Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-κB, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans

All eyes on gas exchange: impact of controlled arterial hypertension on cardiopulmonary function and the effects of high-intensity interval training.

INTRODUCTION: Arterial hypertension (AH) impairs vascular function which, in turn, may reduce cardiopulmonary function. However, the impact of AH on cardiorespiratory fitness (CRF) and its potential mechanisms remains insufficiently investigated. We compared cardiopulmonary function during exercise testing (CPET) between adults with and without AH (part 1) and evaluated the effects of high-intensity interval training (HIIT) in adults with AH on submaximal cardiopulmonary CPET parameters (part 2). METHODS: Thirty-eight adults with AH and 19 controls without AH partook in the study. Adults with AH were randomized into either HIIT or a control group. CPET assessed CRF and submaximal exercise parameters, including the oxygen uptake efficiency slope (OUES), V̇E/V̇CO 2 slope, PETCO 2 , V̇O 2 /work rate (WR) slope, and O 2 pulse. The HIIT intervention consisted of triweekly sessions over 8 weeks. RESULTS: Adults with AH had a 6.5 ml kg -1  min -1 (95% confidence interval: 1.7-11.3) lower CRF, a steeper V̇E/V̇CO 2 slope (moderate-large effect size), lower PETCO 2 (large effect size), flatter V̇O 2 /WR slope (moderate effect size), and lower O 2 pulse (small-moderate effect size) than adults without AH. HIIT improved CRF and altered certain cardio-circulatory parameters in AH, including OUES (small-large effect size), V̇O 2 /WR slope (small-moderate effect size, low precision) and O 2 pulse (small-moderate effect size). However, effects of HIIT on pulmonary-vascular parameters were inconclusive, with large variability observed in the V̇E/V̇CO 2 slope and PETCO 2 . CONCLUSION: Adults with controlled AH might have lower CRF, indicating limitations in pulmonary-vascular and cardio-circulatory organ systems. A short-term 8-week HIIT enhances CRF and cardio-circulatory function, however, evidence is limited for improvements in pulmonary-vascular function.

Humans

Clinical Utility of Ultra-Widefield Swept-Source OCT for Intraocular Tumors: Comparison With Ultrasonography, SD-OCT, and MRI.

PURPOSE: To evaluate the clinical performance of ultra-widefield swept-source optical coherence tomography (UWF-OCT) in the assessment of choroidal tumors and to compare it with ultrasonography (US), spectral-domain (SD)-OCT, and magnetic resonance imaging (MRI). DESIGN: Retrospective diagnostic comparison. SUBJECTS: Thirty-nine eyes from 39 patients diagnosed with choroidal tumors at a single tertiary referral center. METHODS: This retrospective diagnostic comparison evaluated patients diagnosed with choroidal tumors at a single tertiary referral center between January 2023 and August 2025. All patients underwent UWF-OCT imaging at diagnosis. Tumor measurements obtained with UWF-OCT were compared with US, SD-OCT, and MRI. Comparative analysis among imaging modalities and predictors affecting UWF-OCT applicability was performed. MAIN OUTCOME MEASURES: Tumor thickness (mm) and largest basal diameter (LBD, mm) measurements, and complete measurability rate across different tumor size categories. RESULTS: Thirty-nine eyes from 39 patients (mean age 59.2 &#xb1; 16.9 years) were analyzed, including 27 choroidal melanomas (69.2%), 5 metastatic tumors (12.8%), 4 hemangiomas (10.3%), 2 osteomas (5.1%), and 1 (2.6%) indeterminate choroidal melanocytic lesion. UWF-OCT successfully measured both tumor thickness and largest basal diameter (LBD) in 100% (31/31) of small and medium choroidal tumors, substantially outperforming SD-OCT (complete measurement achieved in 63.6% of small tumors, and 0% of medium or large tumors). UWF-OCT measurements were systematically smaller than ultrasonography (thickness: -32.3%, P < .01; LBD: -11.1%, P < .01) and MRI (thickness: -29.2%, P < .01). Mushroom-shaped tumor morphology was the strongest negative predictor of UWF-OCT quality (OR = 0.015, 95% CI 0.001-0.196, P < .01). UWF-OCT's complete measurability was limited in large tumors (12.5%, 1/8). CONCLUSIONS: UWF-OCT provides precise, noninvasive, single-scan assessment of small-to-medium choroidal tumors with detailed structural visualization. It may be particularly useful for dome-shaped tumors, while multimodal imaging with US and MRI remains optimal for complex morphologies. Overall, UWF-OCT represents a valuable tool for diagnosis and treatment planning, with potential utility for longitudinal follow-up in choroidal tumor management.

Humans

Synchronicity of parent-child sleep and potential mechanisms: A systematic review and meta-analysis.

Existing evidence indicates that parent and child circadian rhythms are associated, but studies have mainly examined factors affecting child sleep health. This systematic review addressed two questions: a) is there a synchronous relationship between parent and offspring sleep? and b) what are the potential mechanisms? PubMed, Embase, PsychINFO, and Scopus were searched from inception to April 2025. Forty-six studies comprising over 100000 parent-child dyads across 16 countries were included. Results showed small-to-moderate parent-child synchronicity in sleep duration (r&#x202f;=&#x202f;0.18, 95% CI [0.14, 0.23]), sleep efficiency (r&#x202f;=&#x202f;0.30, 95% CI [0.19, 0.41]), bedtime (r&#x202f;=&#x202f;0.34, 95% CI [0.20, 0.46]), and wake up time (r&#x202f;=&#x202f;0.48, 95% CI [0.24, 0.66]), with stronger effects observed in mother-child dyads. Synchronicity in sleep continuity was moderate, whereas associations in sleep satisfaction were small and non-significant. Mechanisms included genetic and hormonal factors, bedtime routines, shared environments, and attachment. These findings are consistent with family systems theory's premise that sleep is a relational phenomenon. Observed synchronicity in sleep timing may partly reflect shared external constraints like work and school schedules. Most studies were cross-sectional, limiting causal or directional conclusions. Future research should adopt standardized methodologies and longitudinal designs to clarify mechanistic pathways.

Humans

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P&#x202f;<&#x202f;.0001; equivalent to -4.0&#x202f;mmol/mol). Heterogeneity was moderate-to-substantial (I&#xb2; = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P&#x202f;=&#x202f;.31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans

Phylogenomics and female reproductive morphology reframe the classification of the Halymeniales (Rhodophyta).

The red algal order Halymeniales (Rhodophyta) exhibits remarkable morphological and taxonomic diversity but its higher-level relationships remain poorly resolved. Here, we present a comprehensive phylogenomic analysis based on newly generated plastid (170 protein-coding genes), mitochondrial (23 genes), and complete nuclear ribosomal cistron sequences from 56 taxa, complemented with an expanded rbcL dataset encompassing 334 sequences. Our results provide a robust phylogenomic framework for the Halymeniales, offering a taxonomic backbone for future systematic studies. The analyses consistently recover six early-diverging lineages (Acrodiscus, Isabbottia, Norrissia, Pachymenia, Zymurgia, and Tsengia) and two strongly supported larger clades (Halymenia s.l. and Grateloupia s.l.). While most small and recently described genera are monophyletic, several traditional genera (e.g., Halymenia, Cryptonemia, Grateloupia) are poly- or paraphyletic, requiring considerable taxonomic revision. At the family level, the data indicate that reinstatement of the Grateloupiaceae sensu Kim et al. (2021) would entail a revised circumscription of the Halymeniaceae and the recognition of at least five small families to accommodate the early-diverging lineages. Although such a revised classification would result in monophyletic families, it is not supported by morpho-anatomical characters. Instead, we propose a more stable two-family system, recognizing a broadly circumscribed Halymeniaceae that is sister to the Tsengiaceae. Female reproductive characters, particularly the structure of carpogonial and auxiliary cell ampullae, support this two-family system and further characterize many genus-level clades, although substantial convergence across lineages exists.

Phylogeny

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n&#x2009;=&#x2009;16) or vascular imaging (n&#x2009;=&#x2009;14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans

Effect of Narrative-Based Palliative Care on Psychological Stress, Quality of Life, and End-of-Life Acceptance in Elderly Terminal Cancer Patients and Their Families.

ObjectiveThis study aimed to preliminarily evaluate the impacts of narrative-based palliative care on psychological stress, end-of-life acceptance, and quality of life in elderly terminally ill cancer patients and their family caregivers.MethodsThis single-center, small-sample randomized controlled study enrolled 50 elderly terminal cancer patients. Patients were randomly assigned to either the observation group or the control group (n = 25 each). The observation group received narrative-based palliative care, while the control group received routine standard care. Family psychological stress was assessed using the Relative Stress Scale (RSS), and patients' perceived stress was evaluated with the Perceived Stress Scale-10 (PSS-10). Caregiver satisfaction was measured using a hospital-developed questionnaire. Patients' quality of life was evaluated using the SF-36, Chinese Version of the Death Attitude Profile (DAP-C), and Pittsburgh Sleep Quality Index (PSQI), respectively.ResultsBaseline characteristics did not differ significantly between the two groups (P > .05). Post-intervention, the observation group demonstrated significantly lower psychological stress among family members and higher caregiver satisfaction (P < .05). Patients in the observation group reported better quality of life, improved sleep, and greater acceptance of death than those in the control group (P < .05).ConclusionAs a small-sample, single-center study, these findings offer preliminary evidence that narrative-based palliative care may reduce psychological stress in elderly terminal cancer patients and caregivers while enhancing patients' quality of life, sleep quality, and acceptance of death. However, the limited sample size, single-site design, and narrow inclusion criteria restrict generalizability. Larger multicenter trials are needed to confirm these results.

Humans

Effect of SGLT2 inhibitor drugs on triglyceride-glucose (TyG) index in adults: A systematic review and meta-analysis.

BACKGROUND: Insulin resistance is a serious public health concern. The triglyceride-glucose (TyG) index is a simple, cheap, and reproducible surrogate of insulin resistance, and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped cardio-metabolic care beyond glycemic control. METHODS: We followed PRISMA and registered the protocol in PROSPERO (CRD420251056341). We searched PubMed, Scopus, Web of Science, EMBASE, and Cochrane from inception to May 31st, 2026, including observational studies and clinical trials reporting baseline and follow-up TyG in adults. Two reviewers screened records, a third resolved disagreements, data were extracted with a standardized form, and quality was assessed with Cochrane RoB 2.0, the Newcastle-Ottawa Scale, and the JBI checklists. The primary outcome was within-group change in TyG pooled with random-effects (Hartung-Knapp); tests were two-sided with a significance threshold of 0.05. RESULTS: Twelve studies comprising thirteen study arms were included, with a total of 1845 participants. Follow-up ranged from 12 weeks to 5 years. Across studies, SGLT2 inhibitor therapy was associated with a significant reduction in TyG index (mean difference = -0.28, 95% confidence interval [-0.41; -0.14], I2 = 99.5%). Egger's test suggested possible small-study effects, whereas Begg's test and trim-and-fill analysis did not show clear evidence of publication bias; leave-one-out analyses showed that no single study materially influenced the pooled estimate. CONCLUSION: Despite heterogeneity in populations, drug choice, and follow-up duration, SGLT2 inhibitors were associated with a significant decrease in TyG, although small-study effects cannot be excluded.

Humans

The impact of artificial intelligence on critical thinking and clinical reasoning in health professions education: A systematic review and meta-analysis.

BACKGROUND: Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. OBJECTIVE: To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. METHODS: Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. RESULTS: Fourteen randomised controlled trials and seven controlled clinical trials were included (n&#xa0;=&#xa0;21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value&#xa0;=&#xa0;0.00; I2&#xa0;=&#xa0;38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value&#xa0;=&#xa0;0.01; I2&#xa0;=&#xa0;79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. CONCLUSION: AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. PROTOCOL REGISTRATION: CRD42025634074.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n&#xa0;=&#xa0;148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1&#xb7;08, 95% CI 1&#xb7;02-1&#xb7;13; p&#xa0;=&#xa0;0&#xb7;004; I2&#xa0;=&#xa0;44%), driven by the observational studies group (1&#xb7;08, 1&#xb7;02-1&#xb7;14; I2&#xa0;=&#xa0;61%); RCTs showed a directionally consistent but non-significant RR (1&#xb7;12, 0&#xb7;87-1&#xb7;43; I2&#xa0;=&#xa0;0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans

Do adherence-focused interventions in low back pain have an impact on rehabilitation outcomes? A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide. Exercise-based interventions are effective, but adherence remains suboptimal. This systematic review and meta-analysis evaluated the effectiveness of strategies designed to enhance adherence to exercise-based interventions in individuals with LBP in terms of adherence as well as pain and functionality. METHODS: Randomized controlled trials including adults with non-specific LBP were eligible if they compared exercise-based interventions incorporating adherence-enhancing strategies versus exercise alone or usual care. Primary outcome was adherence; secondary outcomes were pain and functionality. Searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Scopus, and PEDro up to May 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Random-effects meta-analyses were performed using standardized mean differences. Certainty of evidence was evaluated using the GRADE approach. RESULTS: Fourteen randomized controlled trials including 1233 participants were included. Risk of bias was low in six studies, with the remainder showing some concerns or high risk. For adherence outcomes, evidence showed no clear effect of adherence-enhancing strategies on either device-measured physical activity (SMD&#x202f;=&#x202f;0.21, 95% CI -0.01 to 0.43; 3 trials, 320 participants; moderate-certainty evidence) or questionnaire-based adherence (SMD&#x202f;=&#x202f;0.33, 95% CI -0.23 to 0.89; 4 trials, 377 participants; very low-certainty evidence). For pain and functionality, moderate certainty of evidence indicated small improvements favoring intervention groups in the medium term. CONCLUSIONS: Strategies to enhance adherence to exercise in LBP show uncertain effects on adherence but may provide small improvements in clinical outcomes in the medium term. Higher-quality trials are needed to strengthen the evidence base.

Adult

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Prognostic Value of Circulating Tumor DNA-Based Minimal Residual Disease for Recurrence-Free Survival in Resectable Gastric Cancer: A Systematic Review and Meta-Analysis with Serial Monitoring Analysis.

BACKGROUND: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) is an emerging biomarker, but its utility in resectable gastric cancer remains incompletely characterized. METHODS: We conducted a systematic review and meta-analysis of eight studies (520 patients) to evaluate the prognostic value of ctDNA-based MRD for recurrence-free survival (RFS) and overall survival (OS) in resectable gastric cancer. RESULTS: In localized resectable gastric cancer (Stage I-III), the setting in which postoperative ctDNA most coherently represents true molecular residual disease after curative-intent surgery, postoperative ctDNA positivity was associated with diminished recurrence-free survival (RFS: HR 12.26, 95% CI 3.30-45.52) and overall survival (OS: HR 8.57, 95% CI 3.06-23.98). The test for subgroup differences between localized and mixed-stage cohorts was not statistically significant (P&#x2009;=&#x2009;0.57), and the numerically higher HR in the localized subgroup should therefore not be interpreted as evidence of a quantitatively stronger prognostic effect. Postoperative ctDNA detection demonstrated substantially stronger prognostic value (overall RFS: HR 10.00, 95% CI 4.53-22.10) compared to preoperative assessment (HR 2.17, 95% CI 1.10-4.28). Both tumor-informed and tumor-agnostic strategies effectively stratified high-risk patients. However, these effect sizes should be interpreted cautiously given the small number of studies and substantial heterogeneity (I2&#x2009;=&#x2009;65-72%). Results from mixed-stage cohorts including Stage IV disease are supportive but should not be considered equivalent to localized-disease findings, as ctDNA in metastatic disease reflects persistent systemic burden rather than minimal residual disease in the postoperative sense. CONCLUSIONS: Postoperative ctDNA-based MRD shows a consistent adverse prognostic association in resectable gastric cancer, with localized disease (Stage I-III) representing the most biologically and clinically coherent setting for interpretation. However, the large pooled hazard ratios (HR 10.00-12.26) should be interpreted as a directionally consistent signal rather than precise quantitative estimates, given the small number of studies, wide confidence intervals, and substantial heterogeneity (I2&#x2009;=&#x2009;65-73%). This heterogeneity is largely driven by substantial variation in postoperative sampling timing (4&#xa0;days to 16&#xa0;weeks) and ctDNA assay characteristics (platform, sensitivity, coverage, variant filtering, and positivity thresholds), which require standardization in future studies. While ctDNA is prognostically valuable, its clinical utility remains unestablished. Prospective randomized trials are needed to determine whether ctDNA-guided strategies improve patient outcomes before routine clinical implementation can be recommended.

Humans

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n&#xa0;=&#xa0;65) or routine nursing only (n&#xa0;=&#xa0;65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6&#xa0;months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6&#xa0;months ranged from small for resilience (D&#xa0;=&#xa0;0.28) and avoidance coping (D&#xa0;=&#xa0;0.26) to moderate for confrontation coping (D&#xa0;=&#xa0;0.60) and resignation coping reduction (D&#xa0;=&#xa0;-0.51), and large for attributional style (D&#xa0;=&#xa0;0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans

The Brazilian contribution to ant toxinology: challenges and perspectives.

Ant toxinology in Brazil is a small but growing field that has revealed wide biochemical diversity and clear potential for bioprospecting therapeutic molecules. This review compiles the Brazilian contribution, focusing on advances in the characterization of venoms from medically and ecologically important species of Dinoponera, Solenopsis, Paraponera, Pachycondyla, Neoponera, and Ectatomma. Brazilian groups applied omics approaches, including transcriptomics and proteomics, to resolve the composition of these venoms and identified peptide-rich arsenals with antimicrobial, antiparasitic, antitumor, and neuroactive activity. Studies of venom phenotypic plasticity showed ecological factors such as diet and seasonality shape venom composition. Two challenges persist: assigning function to still unidentified components and obtaining venom in the quantities that broad analysis requires. The near-term prospects are the rational design of peptide analogues with improved activity and continued bioprospecting of new species, which together position Brazil as a central contributor to ant toxinology.

Animals

Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals