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PubMed2026

Effects of Lactiplantibacillus plantarum KABP051 Probiotic on Body Composition, Microbiome and Mood in Healthy Overweight Adults.

Obesity and mental health disorders are among the greatest public health challenges of the 21st century. Interestingly, an altered microbiome profile has been associated with both conditions. The aim of this randomized, double-blind, placebo-controlled clinical trial was to evaluate the effects of dietary supplementation with a specific probiotic strain (Lactiplantibacillus plantarum KABP051) on body composition and gut microbiome balance, together with measures of mood state, in a population of healthy overweight subjects. Sixty healthy, moderately stressed, nondepressed and overweight or obese volunteers were supplemented for 12 weeks with probiotic (L. plantarum KABP051; 1 billion colony forming units/day) or placebo (microcrystalline cellulose). The KABP051 group experienced significantly greater improvements compared with placebo on body composition measurements, including a reduction in body weight and waist circumference, which decreased in 1.97 ± 0.77 (mean ± SE) kg and 2.15 ± 0.81 (mean ± SE) cm versus placebo at the end of the intervention (both P < .05, mixed model for repeated measures [MMRM] and post-hoc analysis). Microbiome composition improved in KABP051 group, with significant increase in the relative abundance of Lactiplantibacillus spp. versus placebo. Body fat percentage, profile of mood states fatigue, and confusion sub-scores showed a global trend toward improvement compared with placebo, with the change at 12 weeks being significant in the three measurements in post-hoc analysis (P = .015, P = .014, and P = .016, respectively). No serious adverse events were registered during the intervention period. These results suggest that a specific strain of probiotic bacteria (L. plantarum KABP051) may have both metabolic and psychobiotic effects and may be beneficial for enhancing weight loss and body composition, improving energy (less fatigue) and mood levels while embarking on a healthy lifestyle regimen. ClinicalTrials.gov identifier: NCT06808061.

Humans↗

PubMed2026

Rational design of high-productivity perfusion processes for CHO Cells: From growth inhibitory strategies to model-driven optimization.

While perfusion culture for Chinese hamster ovary (CHO) cells offers advantages such as continuous operation and flexibility, it suffers from product loss through cell bleeding and difficulties in reaching high productivity due to sustained rapid cell growth. Growth inhibitory strategies are widely used to enhance productivity in fed‑batch processes; however, their practical implementation and comparative effectiveness in perfusion processes remain insufficiently explored. Meanwhile, process development often relies on costly trial‑and‑error approaches. Here, we systematically compared three growth inhibitory strategies in perfusion culture-low cell‑specific perfusion rate (CSPR), sodium butyrate, and mild hypothermia-with respect to cell growth, metabolism, productivity, and product quality. Genome‑scale metabolic flux sampling analysis revealed that low‑CSPR and sodium butyrate induce a convergent up‑regulation of energy metabolism, correlating with greater gains in specific productivity (qp). Building on this insight, we developed a growth‑kinetic model for the combined low‑CSPR + butyrate strategy, incorporating parameter uncertainty. This model‑guided framework enabled the rational design of two distinct high‑productivity perfusion processes: a sustained mode that achieved robust long‑term stability alongside substantial productivity gains, and a high‑intensity mode that pushed qp and daily volumetric titer to their maxima, with increases of up to 108.94% and 190.36%, respectively, in a model CHO cell line with a moderate baseline productivity. Our study provides a proof‑of‑concept framework for perfusion intensification, from strategy selection to rational process design.

Animals↗

PubMed2026

Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score ≥2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

Humans↗

PubMed2026

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 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↗

PubMed2026

Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.

BACKGROUND: The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. METHODS: We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50 mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. RESULTS: Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. CONCLUSIONS: The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.

Humans↗

PubMed2026

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Early diagnosis of cholangiocarcinoma (CCA) remains challenging because existing diagnostic approaches often lack sufficient sensitivity for reliable detection of early-stage disease. Circulating tumor cells (CTCs) in blood and exfoliated tumor cells (ETCs) in bile represent valuable targets for liquid biopsy-based detection; however, their low abundance and the complexity of clinical sample analysis pose substantial technical challenges for reliable enrichment and identification. Herein, we present a reproducible workflow for isolating and identifying CCA tumor cells from blood for CTCs and bile for ETCs using synthetic cell-surface heparan sulfate (HS) octasaccharide-functionalized magnetic beads (MBs) on integrated microfluidic systems. The method combined sample pre-processing, magnetic bead-based enrichment, controlled low-shear mixing and immunofluorescence-based identification into a unified workflow compatible with distinct clinical sample types. Key operational parameters, including MB concentration, mixing frequency, and pressure settings, were detailed to facilitate consistent performance. Using this workflow, tumor cell capture rates of approximately 70% in bile (for ETCs) and blood (for CTCs) were achieved, with a total processing time of 60-90 min per sample under clinically relevant low-abundance conditions. The platform enables reliable detection of as few as 1 tumor cell per mL of blood or bile. This method provides a practical and adaptable strategy for glycosaminoglycan-mediated liquid biopsy applications and may be extended to other tumor-cell enrichment workflows involving heterogeneous cell-surface interactions.

Humans↗

PubMed2026

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans↗

PubMed2026

Stigma, discrimination-related events, and determinants among adult people living with systemic lupus erythematosus (SLE): Systematic review and indicator-level meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with 0.4 million new cases diagnosed annually. With its wide variety of visible and invisible manifestations, people living with SLE report being exposed to stigmatization, which impacts their personal and professional lives. However, the current literature is unclear on whether healthcare management teams assess this concern during follow-up. This study aims to synthesize existing evidence on the prevalence and determinants of stigma among people living with SLE.MethodsThis systematic review and meta-analysis gathered evidence from observational studies identified from three databases on 16 July 2025. Dual independent screening, data extraction, and risk-of-bias assessment (using the Newcastle-Ottawa Scale) were performed. Results were synthesized using descriptive statistics, narrative synthesis, and indicator-level meta-analyses.ResultsWithin the past two decades, 11 studies comprising 2254 people living with SLE reported and measured stigma- and discrimination-related events using various scales. Stigma was found to be prevalent across its three constructs: interpersonal, perceived, and intrapersonal stigma. This review demonstrated that people living with SLE reported a moderate overall burden of stigma (34.71 [95% CI 26.15, 43.27]), with average stigma scores indicating psychological impact. Additionally, nearly one in two persons (46% [95% CI 28-66%]) experienced at least one form of stigma or discrimination, most commonly social isolation and unfair treatment. Mental health associations were correlated with higher stigma burden.ConclusionThis review demonstrates that stigma and discrimination are not just social challenges but also critical determinants of health. With cautious interpretation, pooled evidence reveals a consistent high prevalence of stigma and discrimination, which act as "toxic" stressors, creating a vicious cycle with psychological stress and psychiatric manifestations and disease activity. There is an urgent clinical need to move beyond a mere biological approach to disease assessment and management and to begin screening for the "invisible" burden of invalidation and discrimination.

Humans↗

PubMed2026

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA ≥85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans↗

PubMed2026

Postoperative Curvature Loss in Three-Level Anterior Cervical Discectomy and Fusion With Zero-Profile Device.

PURPOSE: Cervical curvature loss is a frequent complication following 3-level anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device. Consequently, the capacity of this device to maintain cervical sagittal alignment in 3-level ACDF remains highly controversial. This study aimed to identify potential predictors for postoperative curvature loss (PCL) and evaluate its impact on clinical outcomes. METHODS: A total of 113 patients who underwent ACDF for 3-level cervical degenerative disc disease (CDDD) between January 2021 and December 2023 were retrospectively reviewed. Demographic data, radiological parameters, and clinical outcomes were analyzed. Radiographic measures included cervical curvature, T1 slope, C2-7 sagittal vertical axis, and titanium plate and endplate (TPE) distance. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Statistical analyses were performed using paired and independent t-tests, as well as Pearson correlation coefficients. RESULTS: The average curvature loss was 6.82° from 1 week postoperatively to the final follow-up (p < 0.001). However, the final curvature (11.65°) was maintained, representing a 4.33° improvement compared to preoperative values. Significant correlations were observed between PCL and preoperative curvature (r = -0.368, p = 0.013), preoperative T1 slope (r = -0.546, p < 0.001), ∆T1 slope (r = 0.443, p = 0.002), and ∆TPE distance (r = 0.417, p = 0.004). PCL did not correlate with Japanese Orthopaedic Association (JOA) scores or arm VAS scores at the final follow-up. Nevertheless, patients with a PCL ≥ 6° exhibited significantly higher neck VAS (p = 0.028) and NDI scores (p = 0.041). CONCLUSION: Although contiguous 3-level ACDF with a Zero-Profile device may result in PCL, it preserves an improved cervical lordosis compared to the preoperative baseline. Low preoperative curvature and a low preoperative T1 slope are potentially predictive factors for PCL. Postoperative changes in TPE distance and T1 slope are significantly associated with PCL, suggesting a potential biomechanical link that requires direct validation. Furthermore, PCL may lead to higher neck VAS and NDI scores. Consequently, the Zero-Profile device may require careful consideration in 3-level CDDD patients presenting with low preoperative curvature and a low T1 slope. Importantly, the 6° PCL threshold identified is preliminary and requires prospective validation before clinical application.

Humans↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans↗

PubMed2026

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans↗

PubMed2026

Patient-reported outcome measures within European cohorts of severely injured patients: a systematic review and meta-analysis.

PURPOSE: Severe injury affects multiple health-related domains, yet comprehensive European data on patient-reported outcomes remain limited. This systematic review and meta-analysis evaluates patient-reported outcome measures (PROMs) use and outcomes in severely injured European cohorts. METHODS: A systematic search of four databases up to October 14, 2025, identified European studies from 2000 onward reporting PROMs in severely injured patients. Severe injury was defined as an Injury Severity Score ≥ 16, Glasgow Coma Scale ≤ 8, intensive care unit admission, spinal cord injury, traumatic amputations, or pelvic fractures. Two reviewers independently screened records, with disagreements resolved by a third reviewer. Meta-analysis was performed when ≥ 3 studies reported comparable PROMs at similar follow-up timepoints. RESULTS: Of 2,479 studies, 119 were included. Most cohorts originated from the Netherlands (26%), Norway (18%), and Germany (16%). General severely injured cohorts were most frequently studied (61%), followed by traumatic brain injury (17%), and spinal cord injury (15%). In total, 94 PROMs were used across 277 follow-up timepoints. Health-related quality of life was assessed most frequently (63%), after that anxiety/depression (14%), post-traumatic stress (9%), and social functioning (6%). At one year follow-up, the pooled EuroQol-5D-3 L index score was 0.70 (95% CI 0.62-0.77) and VAS score was 68 (95% CI 60-75), indicating persistent impairment compared to population norms. CONCLUSION: Severely injured patients show persistent impairments with incomplete restoration of pre-injury functioning. Despite increased PROMs use, heterogeneity in selection and outcome reporting limits comparability, underscoring the need for standardised PROM assessment to improve outcome evaluation after severe injury.

Humans↗

PubMed2026

Beyond multidimensionality: a systematic review of recurrent frailty archetypes in community-dwelling older adults.

BACKGROUND: Frailty is a clinically heterogeneous geriatric syndrome commonly summarised using physical or multidomain severity scores. Whether person-centred analyses identify recurring within-frailty configurations has not been systematically examined in community-dwelling older adults. METHODS: We searched PubMed, Embase, MEDLINE, and CINAHL (January 2000-November 2025) for cross-sectional studies using latent class, latent profile, or analogous clustering methods to derive frailty subgroups. Quality was assessed using the AHRQ checklist and a purpose-built appraisal of person-centred model reporting. Study-derived classes were mapped in duplicate to a structured archetype framework developed through comparison of class-defining features across studies. RESULTS: Fourteen reports representing 12 independent datasets from eight countries were included. Six configurations were identified: minimally impaired reference, mobility-physical, nutritional-metabolic, cognitive-predominant, combined cognitive-physical, and psychosocial/mood-predominant. Convergence was measurement-dependent. The reference and mobility-physical configurations recurred across physical-only and multidomain indicator sets, while the combined cognitive-physical configuration appeared across several multidomain frameworks but required cognition to be measured. The remaining configurations emerged only when their defining domains were included. Evidence of prognostic value beyond aggregate frailty severity came from one deficit-index study. Collapsing shared-provenance reports and excluding the boundary-eligible study did not alter recurrence; excluding the Croatian dataset left five configurations recurrent, with the cognitive-predominant configuration supported by one independent dataset. CONCLUSIONS: Person-centred analyses identify recurring within-frailty configurations, but their apparent stability is partly measurement-dependent. A five-configuration core persisted after exclusion of the Croatian dataset, whereas the cognitive-predominant configuration remained weakly replicated. Harmonised indicators and rigorous external validation are needed before clinical application.

Humans↗

PubMed2026

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans↗

PubMed2026

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

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

Pseudouridine↗

PubMed2026

Clinical outcomes of zirconia dental restorations: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival and success rates of zirconia dental restorations (ZDRs) and their complications. DATA & SOURCES: Electronic searches of PubMed, Cochrane, Embase and Web of Science were conducted up to January 1, 2026. Clinical studies with at least 1-year follow-up evaluating zirconia dental restorations in natural teeth were included. Survival rates, success rates, and biological and mechanical complications were analyzed. Risk of bias was assessed using RoB 2, Newcastle-Ottawa Scale (NOS), and Joanna Briggs Institute tools (JBI). Certainty of evidence was evaluated using the GRADE approach. STUDY SELECTION & RESULTS: Sixty-six studies published between 2008 and 2025 were included. Pooled survival rates ranged from 92.9% to 98.7% up to 10 years for single crowns (SCs), 77.6% over 10 to 13 years for fixed dental prostheses (FPDs), 97.4% for resin-bonded FPDs (RBFPDs) over 10 to 15 years, from 50.0% to 52.6% over 9 to 13 years for conventional cantilever FPDs (CFPDs) and 89.0% for inlay-retained FPDs (IRFPDs) over 10 years. Pooled success rates were 46.1% for SCs over 10 years, 40.1% for FDPs over 10 to 13 years, 84.3% for RBDPDs over 10 to 15 years, 12.5% to 22.6% for CFPDs over 9 to 13 years and 70.3% for IRFPDs over 10 years. Biological and mechanical complication rates were 12.1% and 53.9% for SCs at 10 years, 19.4% and 46.7% for FPDs over 10 to 13 years, 50.0% and 37.5% for CFPDs at 9 years, 21.4% and 14.3% for IRFPDs at 3 years, and 3.3% and 8.0% for RBFPDs over 10 to 15 years. Restorations treated with airborne-particle abrasion (APA) combined with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) achieved favorable short-term clinical outcomes, with pooled survival and success rates of 98.6% and 97.7% for SCs, and 98.1% and 70.1% for IRFPDs, respectively. The included studies were assessed as having low to moderate risk of bias using RoB 2, NOS, and JBI tools, but GRADE assessment yielded evidence of very low certainty. CONCLUSIONS: ZDRs generally demonstrated acceptable to excellent short- to long-term survival and success outcomes. Mid- to long-term clinical performance was varied according to restoration types. The RBFPDs had relatively low complication rates, followed by the SCs, the FPDs and the IRFPDs. CFPDs exhibited relatively low success rates and high complication rates. The predominant biological complications were secondary caries and pulpitis or apical periodontitis, while chipping and debonding were the most common mechanical complications. APA treatment followed by application of MDP is capable of producing favorable short-term clinical outcomes. CLINICAL SIGNIFICANCE: ZDRs except for CFPDs could achieve favorable mid- to long-term clinical performance. CFPDs should be conducted with caution.

Zirconium↗