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Association of media use with sleep of children and adolescents: an umbrella review.

Adequate sleep is essential for child and adolescent development, driving extensive research across scientific disciplines. This umbrella review provides a comprehensive overview of existing evidence on media consumption and sleep and thereby lays the foundation for identifying key concepts and gaps. An inclusive systematic search for reviews reporting literature searches was conducted in 02/2021 and updated last in 09/2024. Methodological quality of the included reviews was assessed using AMSTAR-2. We included 84 reviews reporting on the association between media use and sleep in individuals aged 0-18 years. The field is dominated by reviews of low methodological quality, mainly including original cross-sectional studies with subjective measures in older children and adolescents. A total of 475 original articles were covered by the reviews; only 10 of them appeared in at least seven and at most nine reviews. Screen time generally had a negative impact on sleep, though evidence varied from very low to strong. Evidence for effects of conventional books on sleep remains inconclusive. High quality systematic reviews are needed to evaluate robust studies using objective measures of sleep and contemporary media use across all age groups up to adolescence and to explore the impact of non-digital media use on sleep, considering age and gender differences.

Humans

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH&#x2082;O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO&#x2082;/FiO&#x2082;), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6&#x2009;>&#x2009;12.5), the PaO&#x2082;/FiO&#x2082; ratio and Cstat increased significantly after RM (PaO&#x2082;/FiO&#x2082;: 100.8&#x2009;&#xb1;&#x2009;30.3 vs. 125.4&#x2009;&#xb1;&#x2009;38.3&#xa0;mmHg, p&#x2009;<&#x2009;0.05; Cstat: 21.5&#x2009;&#xb1;&#x2009;5.8 vs. 28.0&#x2009;&#xb1;&#x2009;7.0&#xa0;mL/cmH&#x2082;O, p&#x2009;<&#x2009;0.001), Pdriv decreased (19.1&#x2009;&#xb1;&#x2009;3.5 vs. 15.6&#x2009;&#xb1;&#x2009;3.2 cmH&#x2082;O, p&#x2009;<&#x2009;0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6&#x2009;&#x2264;&#x2009;12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

Humans

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6&#x2009;months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250&#x2009;mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4&#x2009;months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0&#x2009;months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8&#x2009;months (95% CI: 3.3-8.2), and median OS was 10.9&#x2009;months (95% CI: 6.0-15.8). Grade &#x2265;3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

Humans

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (&#x223c;19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (&#x223c;6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans

Comparison of analgesic treatments used for ankle sprains in the emergency department.

BACKGROUND: Ankle sprains (ASs) account for approximately 5% of emergency department visits and 40% of all sports-related injuries, causing significant pain and restriction in the range of motion (ROM). This study aims to observe the clinical outcomes of early administration of intravenously administered paracetamol, ibuprofen, and dexketoprofen, which are frequently used in emergency department practice for ASs. For this purpose, pain monitoring and ROM measurements were performed to demonstrate the effectiveness of early functional analgesia. METHODS: This prospective, randomized, double-blind study was conducted between December 2023 and May 2024 on patients diagnosed with grade 1-2 ASs in the emergency department. Patients were divided into three groups and received intravenous dexketoprofen (Group D, n=52), paracetamol (Group P, n=52), and ibuprofen (Group I, n=51). Pain assessment was performed using the numeric rating scale (NRS) and the Wong-Baker FACES Pain Scale (WBS). ROM was evaluated by measuring dorsiflexion ROM (d-ROM) and plantar flexion ROM (p-ROM) angles using a semicircular goniometer. Pre-treatment and 1-h post-treatment measure-ments were compared. RESULTS: In the post-treatment pain assessment, no significant difference was observed between the groups in terms of NRS scores (p=0.352); however, Group I had the lowest WBS scores (p<0.001). Nevertheless, in all three groups, post-treatment pain scores (NRS and WBS) were significantly lower compared to pre-treatment values (p<0.001). Regarding ROM, pre-treatment d-ROM and p-ROM values were similar among the groups (p=0.196) and p=0.287, respectively). Post-treatment measurements revealed that d-ROM was lower in Group I (p=0.034), whereas p-ROM was higher (p=0.011). However, in all groups, ROM values significantly improved after treatment compared to baseline (p<0.001). When pre- and post-treatment changes (&#x394;) in pain scores and ROM values were compared, no statistically significant differences were found between the groups (&#x394;NRS p=0.264, &#x394;WBS p=0.965, &#x394;d-ROM p=0.099, &#x394;p-ROM p=0.073). CONCLUSION: Paracetamol, ibuprofen, and dexketoprofen demonstrated similar efficacy in reducing pain and improving ankle joint ROM during the acute phase of ASs. These findings suggest that the early initiation of analgesic treatment in ASs contributes to clinical recovery.

Humans

A systematic review of sleep hygiene interventions in physically and operationally demanding occupations.

Workers in physically and operationally demanding (POD) occupations (e.g. military personnel, emergency responders, law enforcement) experience disrupted sleep due to irregular schedules and high-stress work environments. Given the importance of sleep for physical and cognitive performance, interventions to improve sleep in POD occupations are crucial yet remain under-researched. To investigate the effectiveness of sleep hygiene interventions in improving sleep quality and quantity outcomes for POD occupations, a systematic review was conducted across five databases (PubMed, CINAHL, SPORTDiscus, PsycINFO, Web of Science) in September 2024. Eligible studies involved workers in POD occupations where a sleep hygiene intervention was compared against a waitlist or passive control. Ten studies were included, eight randomised controlled trials (RCTs) and two non-randomised controlled trials (NRCTs). Narrative synthesis identified Structured Training Programs (n&#x202f;=&#x202f;7), Phone Assistance Programs (n&#x202f;=&#x202f;2), and Single Lecture Interventions (n&#x202f;=&#x202f;1). Evidence certainty ranged from Very Low to Moderate, converging towards Low quality due to imprecision, risk of bias, and indirectness. Structured Training Programs showed moderate improvements in sleep quality and small-to-moderate effects on sleep duration. Phone Assistance Programs had minimal effects, and Single Lecture Interventions had negligible impact. Higher-quality research is urgently needed to assess sleep hygiene interventions in POD occupations.

Humans

Psychological skills training for sport-related outcomes: An umbrella review of evidence credibility and methodological quality.

Psychological skills training (PST) is widely used in sport, but review-level evidence remains fragmented across interventions, populations, outcomes, and methodological standards. This umbrella review synthesized evidence on PST-related interventions for sport-related outcomes, including athletic performance, psychological outcomes, cognitive performance, and sports injury, and evaluated evidence credibility, certainty, and methodological quality. A systematic literature search was conducted on 21 May 2025 in MEDLINE, PsycInfo, PubMed, Scopus, SportDiscus, Web of Science, and CINAHL Complete. Overall, 61 reviews involving 42,106 participants were included; 35 meta-analyses involving 28,076 participants were eligible for quantitative synthesis, and 26 reviews or meta-analyses involving 14,030 participants were summarized qualitatively. Quantitative findings showed generally positive point estimates for mindfulness-based interventions, imagery practice, music-based interventions, neurofeedback, perceptual-cognitive training, and multiple PST interventions, but most findings were weak or non-significant and certainty was generally very low. Qualitative evidence suggested potential benefits, but conclusions varied according to intervention definition, delivery, outcome measurement, and methodological quality. Evidence was more developed for athletic performance and psychological outcomes than for cognitive performance and sports injury. Overall, PST-related interventions may benefit sport-related outcomes, but conclusions should remain cautious because of low certainty, methodological heterogeneity, and limited evidence credibility.

Humans

Evaluation of oral health-related quality of life following pulp therapy or extraction in paediatric patients: a systematic review.

BACKGROUND: Treatment decision between pulp therapy and extraction for compromised teeth in paediatric patients remains a topic of debate. While both approaches address the associated pain, their long-term impact on children's well-being remains unclear. This systematic review aimed to analyse and compare the impact of pulp therapy and extraction on OHRQoL in paediatric patients. METHODS: This review was conducted in accordance with PRISMA guidelines. A comprehensive search was performed in multiple electronic databases. Methodological quality and risk of bias were evaluated using the RoB 2 tool for randomised controlled trials, ROBINS-I tool for non-randomised trials, and the Newcastle-Ottawa Scale for observational studies. RESULTS: Seven studies comprising a total of 1367 participants met the inclusion criteria. The results indicated that pulp therapy was associated with superior OHRQoL outcomes compared to extraction. Children who underwent pulp therapy reported lower anxiety, better emotional well-being, and higher parental satisfaction. Given the heterogeneity among the studies, a narrative synthesis was performed. CONCLUSION: Pulp therapy may offer better OHRQoL outcomes than extractions in paediatric patients by preserving function, reducing anxiety, and minimising long-term complications. However, these findings should be interpreted cautiously since&#xa0;the available evidence was limited and of low to very low certainty. Further well-designed randomised controlled trials are required.

Children

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day &#x2264; 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n&#x2009;=&#x2009;60) and a control group (n&#x2009;=&#x2009;60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P&#x2009;<&#x2009;0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P&#x2009;<&#x2009;0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans

Improving Patient Comfort of Vibratory Anesthetic Devices With a Dampener: A Pilot Study.

BACKGROUND: Vibratory anesthetic devices (VADs) reduce dermatologic injection pain, but their vibration can feel harsh at sensitive anatomical sites. Simple modifications improving patient comfort may enhance VAD adoption. OBJECTIVE: The authors evaluated whether dampening VAD vibration with a cotton buffer improves patient comfort and characterized tactile features influencing preferences. MATERIALS AND METHODS: In a single-site, participant-blinded pilot study (N = 53), adults received a dampened VAD (D-VAD) and standard VAD (S-VAD) at 5 sites-lateral nasal wall, submalar cheek, ear helix, lateral neck, and dorsal forearm-in randomized, contralateral application. Site-specific preference was analyzed with binomial and Cochran Q tests; demographic associations with univariate analyses. Word2vec and hierarchical clustering analyzed qualitative reasons behind patient preference. RESULTS: D-VAD was preferred at all sites across demographics-lateral nasal wall (88.7%), submalar cheek (84.9%), ear helix (88.7%), lateral neck (77.4%), and dorsal forearm (75.5%) (all p < .001), with strongest preference at face and head/neck (p = .018). Computational semantics analysis of qualitative responses identified 6 themes driving preference: Smoothness, Gentleness, Controlled, Low Frequency, Low Intensity, and Less Bothersome. CONCLUSION: Dampening VAD vibration with a cotton buffer enhances comfort across sensitive sites, with reduced harshness and smoother sensation underlying preference. This simple modification may improve patient experience, encouraging broader VAD adoption.

Humans

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult

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

Reliability-aware hierarchical learning for Chagas disease screening from 12-lead ECGs: tackling label uncertainty and class imbalance.

Objective.Chagas disease, a neglected tropical disease (NTD) with significant cardiovascular impact, remains underdiagnosed in resource-limited regions. Electrocardiogram (ECG) screening offers a low-cost tool for detecting cardiac involvement, yet algorithm development is challenged by label noise, data scarcity, and the latent nature of infection. This study proposes a robust ECG-based screening framework that explicitly addresses these constraints.Approach.We introduce aReliability-Aware Hierarchical Learningstrategy that calibrates supervision according to data provenance, prioritizing serology-confirmed labels over noisy self-reports. To mitigate data scarcity, we compare a specialized convolutional neural network (CNN) trained from scratch with a transfer learning approach based on a Spatio-Temporal ECG foundation Model (FM). Performance is evaluated across varying data scales, and the representation structure is analyzed to interpret model behavior.Main results.On the official hidden test set of the George B. Moody PhysioNet/Computing in Cardiology Challenge 2025, our approach achieved a Challenge Score of 0.163. We observe that while the specialized CNN performs competitively in data-rich regimes, the FM exhibits superior robustness in extreme low-resource settings. Furthermore, performance reaches a plateau imposed by underlying disease physiology. Bimodal score distributions suggest that models distinguish established cardiomyopathy from indeterminate infection, which remains electrophysiologically indistinguishable from healthy controls.Significance.These findings clarify both the potential and intrinsic limits of ECG-based AI screening for NTD-associated cardiac involvement. Reliability-aware supervision and data-efficient transfer learning provide a practical framework toward scalable and clinically meaningful ECG screening systems in resource-constrained environments.

Humans

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy

Neighborhood Deprivation and Screening Mammography Utilization: A Retrospective Cross-Sectional Study.

RATIONALE AND OBJECTIVES: Access to screening mammography reduces breast cancer mortality disparities. The Area Deprivation Index (ADI) is a validated measure of neighborhood socioeconomic disadvantage linked to adverse health outcomes. There is limited data evaluating mammography utilization among patients residing in areas of higher deprivation. This study evaluated the association between ADI and screening mammography utilization within an accountable care organization (ACO) affiliated with a multicenter academic medical center in the Upper Midwest. METHODS: This retrospective cross-sectional study included women aged 40-85 years attributed to the ACO in 2022, based on Wisconsin Collaborative for Healthcare Quality criteria. The primary outcome was receipt of screening mammography within two years. The primary exposure was ADI, analyzed by decile (ordinal) and as low (deciles 1-5) versus high (deciles 6-10) deprivation. The logistic regression models evaluated associations between ADI and screening, unadjusted and adjusted for age, race, ethnicity, and preferred language. RESULTS: Among 7463 participants with geographic data, 74.4% completed screening. Screening rates were 75.7% in low-deprivation areas versus 66.2% in high-deprivation areas. Increasing ADI decile was associated with reduced screening in unadjusted (OR 0.891, 95% CI 0.87-0.91, p<0.001) and adjusted analyses (OR 0.897, 95% CI 0.88-0.92, p<0.001). Black participants (OR 0.444, p<0.001) and individuals preferring non-English languages (OR 0.333, p<0.001) had lower screening odds after adjustment. CONCLUSION: Higher neighborhood deprivation is independently associated with lower screening mammography utilization. Targeted, equity-focused interventions addressing neighborhood, racial, and language-related barriers are needed to reduce screening disparities.

Area deprivation Index

Optimization of a niosomal formulation for Quercetin delivery: Comparative effects on growth performance, antioxidant and immune responses, and disease resistance against Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

Quercetin (QUR) is a flavonoid with antibacterial and antioxidant properties that has been studied for its effects on fish health and the immune system. Due to the low bioavailability of QUR, the present study was primarily aimed at developing a niosomal formulation of QUR to enhance its bioavailability and therapeutic properties. The performance of niosomal QUR was then compared with that of its free form by evaluating their effects on the growth and immune system of rainbow trout, Oncorhynchus mykiss. For this purpose, an optimal QUR-containing niosome was formulated by testing different proportions of cholesterol, surfactant, and stabilizer, and the niosomes were then added to the fish diet. A QUR-free diet and a diet containing QUR-free niosomes (QFN) were considered control groups. Niosomes prepared at low hydrophilic-lipophilic balance (HLB) values showed higher QUR entrapment efficiency (QUR-EE%) (P&#x202f;<&#x202f;0.01). An increase in the molar ratio of cholesterol to surfactant significantly reduced QUR-EE% (P&#x202f;<&#x202f;0.05). A surfactant/cholesterol/stabilizer ratio of 1:1:0.1 increased QUR-EE% (P&#x202f;<&#x202f;0.05). The particle size of the niosomes was also affected by HLB and the surfactant/cholesterol/stabilizer ratio. Low HLB values resulted in smaller particle sizes (P&#x202f;<&#x202f;0.01). Furthermore, a surfactant/cholesterol/stabilizer ratio of 1:1:0.1 resulted in the smallest niosomal particle size (P&#x202f;<&#x202f;0.05). The presence of diacetyl phosphate as the stabilizer in the formulation improved the niosomal zeta potential to -40.55&#x202f;mV. The optimal niosomal formulation (HLB&#x202f;=&#x202f;6.6; surfactant/cholesterol/stabilizer ratio of 1:1:0.1) remained stable at 2&#x202f;&#xb0;C over 10 days of storage, as the niosomal QUR content and size did not show significant changes during this period (P&#x202f;>&#x202f;0.01). After preparation of the diets containing the optimal niosomal QUR, fish were fed the experimental diets for two months. QUR, in both niosomal and free forms, resulted in better growth performance than the QUR-free diets (P&#x202f;<&#x202f;0.01). There were no significant differences in growth performance between the free and niosomal forms of QUR; however, 500&#x202f;mg/kg QUR showed significantly better growth performance than 250&#x202f;mg/kg QUR (P&#x202f;<&#x202f;0.01). Although both the niosomal and free forms of QUR enhanced immune and antioxidant components in the fish, the effects of the niosomal form were more significant (P&#x202f;<&#x202f;0.01). In addition, QUR in both free and niosomal forms reduced fish mortality after challenge with Streptococcus iniae. In conclusion, the results of this study suggest that the niosomal form of QUR has strong potential for improving the immune system of fish and increasing resistance to S. iniae infection.

Animals

Structured robotic colorectal training in a non-tertiary NHS hospital: a 502-case consecutive cohort implementation study.

Robotic-assisted colorectal surgery has expanded rapidly across NHS practice in the UK. Structured unit-wide training pathways are essential for safe technology adoption, yet published outcome data from non-tertiary hospitals remain limited. This study describes the implementation and feasibility of a unit-wide robotic colorectal program at a high-volume non-tertiary hospital, reporting outcomes across 502 consecutive resections performed by eight consultant surgeons and presenting these in the context of nationally published benchmarks. A retrospective cohort study of 502 consecutive robotic colorectal resections performed at York Teaching Hospital between May 2022 and December 2025. Eight consultant surgeons (A-H) participated in a structured four-phase training pathway incorporating simulation training, proctored cases, complexity-based case progression, and formal credentialing. Primary outcomes were 30-day mortality, unplanned return to theatre (RTT), and anastomotic leak (AL). Anastomotic leak was calculated using only patients who underwent anastomosis as the denominator. Procedure-stratified and individual surgeon outcomes with 95% confidence intervals were reported. Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to evaluate learning curves. Outcomes are presented descriptively alongside nationally published reference data; no formal statistical comparison against national benchmarks was performed. 502 robotic colorectal resections were performed. Mean patient age was 70.0 &#xb1; 11.3&#xa0;years; 58.4% were male. Median ASA grade was III. The indication was malignancy in 89.2% of cases. Length of stay was non-normally distributed and is therefore reported using median and interquartile range in the revised analysis. Key outcomes: - 30-day mortality: 1.0% (5/502; 95% CI 0.4-2.3%) - Unplanned return to theatre (RTT): 5.2% (26/502; 95% CI 3.6-7.5%) - Anastomotic leak (AL): 3.3% (15/450; 95% CI 2.0-5.5%; denominator = patients with anastomosis) - 30-day unplanned readmission: 5.0% (25/502; 95% CI 3.4-7.2%) - Conversion to open surgery: 3.6% (18/502; 95% CI 2.3-5.6%) - Lymph node yield &#x2265;12: 91.3% of cancer resections - R0 resection rate: 95.1% of cancer resections All primary outcomes fell within or below the published reference ranges used for descriptive context. RA-CUSUM trajectories were heterogeneous: no surgeon crossed the predefined upper control limit, but several curves showed later upward movement. Accordingly, the analysis is interpreted as safety surveillance rather than evidence of uniform performance improvement. RA-CUSUM monitoring showed that no surgeon crossed the predefined upper control limit; however, heterogeneous trajectories precluded a claim of uniform performance improvement.

Humans