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PubMed2026

Effects of music interventions on seizure outcomes in people with epilepsy: a systematic review and meta‑analysis.

OBJECTIVES: To evaluate effects of music interventions on seizure outcomes in people with epilepsy. METHODS: We performed a systematic review and meta‑analysis of controlled and single‑arm studies. Searches were conducted in four English databases, two trial registries, and three Chinese databases, up to October 11, 2025. Dichotomous outcomes were pooled as odds ratios (ORs) and continuous outcomes as mean differences or standardized mean differences (SMD, Hedges' g) using random‑effects models. Heterogeneity was assessed with Cochran's Q and I2. Preplanned subgroup and leave‑one‑out sensitivity analyses examined control type and study influence. Risk of bias and evidence certainty were appraised. RESULTS: Fifteen studies were included. Single‑arm syntheses suggested benefit: pooled curative‑effect rate 0.715 (95 % CI 0.584-0.846) and pre-post IED reduction -0.51 (95 % CI -0.88 to -0.13). Controlled between‑group estimates were imprecise and heterogeneous. Pooled OR for seizure response was 2.71 (95 % CI 0.61-12.12, I2 = 81.2 %, p = 0.19). IED responder OR was 4.57 (95 % CI 0.84-24.86, I2 = 68.9 %). IED frequency SMD was -1.48 (95 % CI -3.06 to 0.10, I2 = 95.2 %). Seizure‑frequency SMD across controlled studies was -0.004 (95 % CI -1.772 to 1.763, I2 = 95.6 %). Results were sensitive to individual studies and limited by small samples and variable comparators. CONCLUSIONS: Music interventions show promising within‑study effects on seizure outcomes, but controlled evidence is inconclusive due to high heterogeneity and imprecision. High‑quality, adequately powered randomized trials with standardized interventions and matched active controls are needed.

Humans↗

PubMed2026

Heterogeneity in Teriflunomide Treatment Arms: A Systematic Review and Meta‑Regression of Randomised Multiple Sclerosis Trials.

BACKGROUND: Teriflunomide is widely used as an active comparator in Phase 3 randomised trials for relapsing multiple sclerosis (RMS). Temporal changes in disease activity within teriflunomide-treated cohorts have not been systematically examined. OBJECTIVES: To assess temporal trends in relapse and disability outcomes across teriflunomide arms of Phase 3 multiple sclerosis (MS) trials and identify predictors of between-trial heterogeneity. METHODS: We performed a systematic review and meta-analysis of Phase 3 randomised controlled trials including a teriflunomide arm. PubMed, Scopus, and ClinicalTrials.gov were searched up to October 2025. Annualised relapse rate (ARR) and 12- and 24-week confirmed disability worsening (CDW) were extracted together with baseline characteristics. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses, meta-regression, and sensitivity analyses were performed. RESULTS: Twelve teriflunomide cohorts from eight trials involving 4,900 adults with RMS were included. ARR ranged from 0.11 to 0.37 with substantial heterogeneity (I2 = 94%). Trial start year was inversely associated with ARR and explained a large proportion of between-study variability in exploratory meta-regression analyses. Confirmed disability worsening outcomes also showed substantial heterogeneity with a weaker trend toward lower event rates in more recent trials. CONCLUSION: Teriflunomide-treated trial populations have shifted toward lower relapse activity over time, and trial start year was the principal predictor of between-trial heterogeneity in ARR in exploratory analyses. These findings most plausibly reflect evolving recruitment and diagnostic practices rather than changes in drug efficacy. Accounting for these temporal dynamics is essential when interpreting outcomes from RMS trial using teriflunomide as comparator.

Humans↗

PubMed2026

Influence of endodontic access on the fracture resistance, retention and microleakage of full-coverage restorations in vitro: A systematic review and meta-analysis.

BACKGROUND: Endodontic access through retained full-coverage restorations (FCRs) is a preferred option for patients because of its high cost-effectiveness. However, the clinical performance of FCRs after repaired access cavity remains insufficiently characterized. This systematic review investigates the effects of endodontic access cavity preparation through retained FCRs on fracture resistance, retention, and microleakage based on in vitro studies. METHODS: A comprehensive search was performed in PubMed, Web of Science, and Scopus databases. Studies investigating the influence of endodontic access on the fracture resistance, retention, and microleakage of FCRs were included. Two independent reviewers conducted study selection, data extraction, and risk-of-bias assessment using the QUIN tool. Meta-analysis was employed to estimate fracture resistance and retention, with sensitivity analysis and subgroup evaluation also performed. Microleakage was summarized qualitatively. RESULTS: Twentythree studies were included: fracture resistance (n = 15), retention (n = 5), and microleakage (n = 3). Endodontic access significantly reduced fracture resistance for zirconia (p = 0.0002) and lithium disilicate (LD) restorations (p = 0.007), but not for resin-matrix ceramic (RMC) restorations (p = 0.25). Abutment tooth type contributed to heterogeneity within the LD and RMC subgroups. Retention was significantly reduced when access cavities were left unrepaired (p = 0.03), whereas appropriate repair protocols restored or enhanced retention relative to baseline. Accelerated aging increased microleakage in retained FCRs. Surface pretreatments and flowable resin liners tended to reduce microleakage, but findings were inconsistent. CONCLUSIONS: Endodontic access significantly reduces fracture resistance of zirconia and LD FCRs, whereas RMC restorations show no significant change. Appropriate repair protocols can restore or improve retention, potentially exceeding original values. Limited evidence suggests that effective sealing is achievable with appropriate materials. However, well-designed and in-vivo researches are needed to provide more detailed clinical guidance. CLINICAL SIGNIFICANCE: When performing endodontic access through retained FCRs, reduced fracture resistance must be carefully considered for zirconia and LD restorations, while RMC restorations may be exempt from this concern. Loss of retention with access can be restored after repair. Surface pretreatment and flowable resin liners help decrease microleakage.

Humans↗

PubMed2026

Application of musculoskeletal ultrasound in postoperative rehabilitation assessment and monitoring after rotator cuff repair: A systematic review.

BACKGROUND: The development of rehabilitation protocols after rotator cuff repair has long lacked objective benchmarks. Traditional time‑based regimens are limited by considerable inter‑individual variability and an increased risk of re‑tear. Musculoskeletal ultrasound allows dynamic assessment of tendon healing and muscle morphology, yet evidence for directly linking its use to rehabilitation decisions remains scarce. OBJECTIVE: To systematically synthesize the evidence on the use of musculoskeletal ultrasound monitoring to inform rehabilitation decision‑making after rotator cuff repair. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines, we searched PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data from January 2020 to April 2026. Original studies were included if they involved patients who had undergone rotator cuff repair, used musculoskeletal ultrasound (including gray‑scale ultrasound, elastography, etc.) to evaluate the rotator cuff tendons or shoulder muscles, and reported at least one parameter related to rehabilitation decision-making or functional outcomes. RESULTS: Eleven studies were included. Shear wave velocity (SWV), cross‑sectional area (CSA), and echo intensity (EI) were the most frequently reported ultrasound parameters. Available evidence indicated that SWV increased progressively after surgery, with an overall increase of approximately 22% to 25% from one week to 12 months postoperatively. This dynamic trajectory may serve as a reference baseline for judging rehabilitation progress. An abnormally elevated SWV in the early postoperative period was associated with an increased risk of re‑tear, suggesting that a more conservative rehabilitation strategy should be adopted. Tendon stiffness measured at 12 weeks after surgery independently predicted long‑term return to sport. Regarding muscle parameters, changes in CSA and EI were positively correlated with shoulder function scores, and the combination of these two parameters effectively identified patients with rehabilitation bottlenecks. CONCLUSION: Musculoskeletal ultrasound parameters are associated with the initiation of active movement, adjustment of exercise load, prediction of return‑to‑sport prognosis, and identification of retear risk. Among these, SWV shows particular promise as an objective monitoring parameter for supporting rehabilitation assessment after rotator cuff repair. Future randomized controlled trials are needed to determine whether ultrasound-informed assessment can improve rehabilitation outcomes compared with traditional time-based regimens, and to establish standardized measurement protocols and clinically applicable reference values. Key findings of this review are summarized in S1 File.

Humans↗

PubMed2026

Multi‑omics approaches to decipher the molecular mechanisms of exercise‑mediated bone protection: From mechanistic insights to personalized exercise prescription (Review).

The global burden of bone metabolic disorders necessitates a shift from generic exercise recommendations toward personalized prescription strategies. Exercise confers skeletal protection through mechanotransduction, yet the underlying molecular networks remain incompletely understood. Multi‑omics technologies, including transcriptomics, proteomics, metabolomics and single‑cell spatial approaches, have revolutionized the capacity to decode exercise‑mediated bone adaptation at the systems level. The present review synthesizes current single‑omics landscapes and integrative multi‑omics analyses that elucidate the core regulatory networks, mechanobiological coupling mechanisms and multiorgan crosstalk that are implicated in the bone response to mechanical loading. Translational applications across clinical scenarios such as osteoporosis, osteoarthritis and disuse bone loss are evaluated, and the technical, analytical and translational challenges limiting clinical implementation are addressed. Finally, the present review provides a framework for translating multi‑omics molecular signatures into personalized exercise prescriptions for optimized skeletal health.

Humans↗

PubMed2026

Nonviral transposon‑engineered stem cells characterization: dose‑dependency between vector copy number and transgene expression.

Genetically engineered stem cells hold substantial promises for advancing regenerative medicine, yet ensuring their genomic safety remains a critical challenge. A key safety concern is vector copy number (VCN), which defines the number of integrated transgene copies per genome. Although ddPCR is used to assess VCN in virally transduced cells, its application in transposon‑engineered systems is limited. In this study, we extended VCN determination to non‑viral, transposon‑engineered stem cells. In alignment with FDA recommendations, the primary objective was to establish a robust and quantitative framework for interim VCN determination at the time of lot release. Specifically, we demonstrate that reliable interim VCN estimates increase in a dose‑dependent manner with increasing plasmid input. In addition, strong linear correlations between VCN and both EGFP median fluorescence intensity (MFI) and gene‑of‑interest (GOI) protein expression validate the accuracy of this framework. Furthermore, comparison of two distinct GOIs revealed gene‑specific differences in expression efficiency. Together, these findings validate a standardized VCN determination workflow that quantitatively links plasmid dose, genomic integration, and functional transgene expression. This workflow provides a systematic characterization of engineered cells, offering comprehensive information to support downstream risk‑based analyses to ensure the genomic safety and stability of the final cell product.

Transgenes↗

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

Imaging‑based models for predicting cerebrovascular complications of carotid stenosis.

This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (≥ 18 years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C‑statistic/area under the curve (AUC)) and calibration (calibration‑in‑the‑large, calibration slope, observed‑to‑expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable‑selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high‑risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast‑enhanced ultrasound (CEUS)) or technical protocol (e.g. 3 T versus 1.5 T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.

Humans↗

PubMed2026

Randomized Trial of Intensive Nurse-Led Follow‑Up Versus Standard Care in Inflammatory Bowel Disease.

BACKGROUND:  Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy. METHODS:  Patients were randomized (1:1) to intensive nurse follow‑up (Arm A) or standard care (Arm B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD‑Disk score in W12. Secondary outcomes were W52 reduction, robust response (> 20-point improvement), and IBD-Disk remission (score < 40). RESULTS: Overall, 98 patients were randomized (Arm A: n = 50; Arm B: n = 48) with similar baseline characteristics. Mean baseline IBD‑Disk scores were 49.2 ± 20.7 in Arm A and 42.0 ± 19.8 in Arm B (p = 0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1 ± 22.9 vs. 10.1 ± 20.1, p = 0.09). At W52, improvement was greater in Arm A (18.4 ± 20.7 vs 9.4 ± 17.8; p = 0.08). More patients achieved robust response in Arm A (49% vs 21%, p = 0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p = 0.045). CONCLUSIONS:  In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse‑led follow‑up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient‑centered outcomes.

Humans↗

PubMed2026

Understanding Suicide through Coroners' Narratives: implications for primary care from a mixed‑methods study of 157 Coroners' reports.

Suicide is a major public health concern, and general practice is often a recent point of contact before death. While mental illness is well recognised, the broader social and contextual factors influencing suicide risk remain under-reported in primary care and epidemiological research Aim To describe the demographic, clinical, and psychosocial characteristics of individuals who died by suicide, integrating coronial quantitative data with qualitative narrative accounts to identify implications for primary/ secondary care and public health. Design and setting Explanatory sequential mixed‑methods study of 157 consecutive deaths by suicide recorded by coroners (2018-19) across five English local authorities. Method Demographic, clinical, and social data were extracted from coroners' records and summarised descriptively. Narrative case summaries were coded and analysed thematically to identify contextual, relational, and service factors preceding death. Results Of 157 individuals: 79% were male; 65% lived in the most deprived IMD quintile; 85% had a diagnosed mental health condition; 62% had a long‑term physical illness; 41% had a previous suicide attempt. About half consulted a GP in the preceding three months; mental health featured in about half of those consultations. Common stressors were relationship breakdown (37.2%), housing instability (22.1%), and work pressures (18.2%). Seven interlinked themes were identified: Mental health; Alcohol/Substance use, Physical health; Social connectedness; Life course trauma, Socioeconomic and Structural Vulnerability; Healthcare access. Service transitions were key vulnerability points Conclusion Coroners' records offer important insights into the complex circumstances preceding suicide and highlight opportunities for GPs to recognise intersectional complexity and support integrated, cross-sector suicide prevention approaches.

General Practice↗

PubMed2026

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

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans↗

PubMed2026

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105 kg P₂O₅ ha⁻¹) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B‑type starch granule formation. Starch granule‑associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch‑synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation‑related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain‑filling intensity and duration, and were associated with the highest theoretical grain weight (50.70 mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210 kg P₂O₅ ha⁻¹) was associated with disrupted inter‑tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C‑type starch granules (0∼5 µm) at 7 DPA, yet by maturity achieved the highest proportion of large A‑type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome‑related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue‑specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum↗

PubMed2026

Robust optimisation for photon radiotherapy: A scoping review of models, paradigms, and reporting.

BACKGROUND AND PURPOSE: Robust optimisation offers an alternative to conventional margin-based photon radiotherapy planning by explicitly modelling uncertainty, but practice is variable and not standardised. MATERIALS AND METHODS: A scoping review was conducted to map robust optimisation for photon external beam radiotherapy. Electronic searches of Scopus, PubMed and Google Scholar (2000-2025, English language) identified planning studies that incorporated modelled uncertainties into the optimisation process and reported at least one robustness-related outcome. Data were charted on clinical context, uncertainty models, optimisation paradigms, robustness metrics and evidence for clinical implementation. RESULTS: Seventy-one studies were included. Most investigated prostate, breast or lung cancer and used intensity-modulated radiotherapy or volumetric-modulated arc therapy in commercial or research treatment planning systems. Scenario-based worst-case (minimax) optimisation was the dominant paradigm in clinically oriented work, while chance-constrained, conditional value at-risk, distributionally robust and adaptive formulations were confined to small methodological series. Uncertainty modelling focused mainly on rigid set-up error; fewer studies incorporated respiratory motion, inter-fraction anatomical change, dose-calculation uncertainty or biological variation. Robustness was evaluated with diverse scenario-based dose-volume metrics, probabilistic coverage measures, composite robustness indices and, less often, biological endpoints. Direct clinical implementation reports were scarce. CONCLUSION: Robust photon planning is technically feasible and generally maintains or improves target coverage and organ sparing compared with margin-based planning. However, heterogeneity in uncertainty models, optimisation configuration and robustness reporting limits comparison and synthesis. Pragmatic minimum standards are proposed to support future consensus and wider clinical adoption.

Humans↗

PubMed2026

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress↗

PubMed2026

Sex-stratified mortality trends in preterm birth complications in Sierra Leone: progress, persistence, and equity implications.

BACKGROUND: Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. OBJECTIVE: To examine two‑decade trends in sex‑stratified mortality from preterm birth complications using standardized equity indicators. METHODS: We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). RESULTS: Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. CONCLUSION: Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2.

Humans↗

PubMed2026

Meta-analysis of growth and inactivation kinetics of Legionella.

Quantitative risk assessments intended to inform evidence-based water management plans and public health targets for Legionella in engineered water systems are constrained by fragmented and heterogeneous growth and inactivation kinetics. We conducted a meta-analysis of 25 growth and 39 thermal- and chemical-inactivation studies, fitting microbial persistence models to harmonize parameters. Nonlinear models outperformed first-order formulations, indicating that lag phases and resistant or protected subpopulations are central to Legionella persistence. Random forest analysis identified environmental and methodological drivers of variability based on 226 growth rates and reduction times for thermal (209) and chemical (135) inactivation. Growth was primarily governed by temperature, nutrient availability, and compatible Legionella-host pairings; thermal inactivation by quantification method, temperature, and turbidity; and chemical inactivation by inoculum size, disinfectant type, concentration, and host-associations. Accordingly, temperature-dependent growth parameters and exposure metrics for heat, free-chlorine, and monochloramine, expressed as TT (Temperature×time) and CT (Concentration×time), were derived as condition-specific inputs for predictive models. Growth optima around 37-40 °C, together with lag-time estimates, indicate that hot-water temperature setbacks and energy-saving practices may favor Legionella proliferation under repeated or prolonged lukewarm exposure. Culture- and viability-based TT differences highlight the need to consider viable‑but-non-culturable persistence in monitoring programs. CT comparisons suggest monochloramine may be advantageous because of its lower apparent sensitivity to host-associated protection. Although limited by restricted experimental conditions, the findings show that predictive models should account for microbial ecology, water matrix effects, and quantification endpoints. Future kinetic studies should prioritize realistic multi-host systems, strain pre-adaptation, complementary viability measurements, and standardized protocols and reporting to ensure reproducibility and enable robust system-level predictive modeling.

Legionella↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗

PubMed2026

Association of lipoprotein-associated phospholipase A2 with recurrence risk and its predictive value in large artery atherosclerotic stroke.

OBJECTIVE: To investigate the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with large artery atherosclerotic (LAA) stroke and its predictive value for recurrence. METHODS: We consecutively enrolled 412 acute LAA stroke patients. Using a cutoff of 200 ng/mL, patients were divided into high and low Lp-PLA2 groups, and into recurrence and non‑recurrence groups based on 1‑year follow‑up. Baseline characteristics, lipid profiles, National Institutes of Health Stroke Scale (NIHSS) scores, and vascular stenosis degree were compared. Binary logistic regression and Receiver Operating Characteristic (ROC) analysis were used to identify independent risk factors and evaluate predictive value. RESULTS: The high Lp-PLA2 group had significantly higher low-density lipoprotein cholesterol (LDL-C), small dense low-density lipoprotein cholesterol (sdLDL-C), prevalence of severe stenosis (≥70%), and proportion of NIHSS > 15 (all P < 0.05). The recurrence group showed elevated Lp-PLA2, higher LDL‑C and sdLDL-C, more severe neurological deficits, and more severe stenosis (all P < 0.001). Multivariable regression identified elevated Lp-PLA2 (per 10 ng/mL: OR = 1.139, 95% CI: 1.089-1.191), moderate (OR = 3.145) and severe (OR = 11.663) neurological deficits, and severe stenosis (OR = 9.390) as independent risk factors for recurrence (all P < 0.05). The Area Under the Curve (AUC) of Lp-PLA2 was 0.75 (95% CI: 0.69-0.82), with an optimal cutoff of 208.95 ng/mL. CONCLUSION: Elevated Lp-PLA2 is associated with adverse lipid profiles, more severe neurological deficits, and greater vascular stenosis in LAA stroke patients, and independently predicts 1‑year recurrence. Lp-PLA2 shows moderate predictive value, supporting its potential for risk stratification.

Humans↗

Results for “Meta&#x2011;analysis”

Results for “Meta‑analysis”