Pediatric sepsis, a major cause of acute lung injury (ALI), involves a dysregulated host response. Cuproptosis is a novel copper-dependent cell death process regulated by Ferredoxin 1 (FDX1). However, its role in pediatric sepsis-associated ALI is unknown. This study investigated the upstream regulation mechanism of FDX1, and its role in pediatric sepsis-related ALI.

Peripheral blood mononuclear cells (PBMCs) were collected from septic children and healthy controls. All enrolled pediatric subjects were divided into three groups: healthy control group (N = 40), sepsis without ALI group (N = 30), and sepsis with ALI group (N = 30). The clinical significance of FDX1, steroidogenic factor 1 (SF1), and Jun proto-oncogene (cJUN) was assessed by qRT-PCR. A septic ALI cell model was established using LPS-treated BEAS-2B cells. Functional assays (CCK-8, TUNEL, ELISA) assessed viability, apoptosis, and inflammation. An in vivo cecal ligation and puncture (CLP) model was employed to confirm the role of FDX1. Molecular mechanisms (transcriptional regulation, protein interaction) were examined via ChIP, dual-luciferase, and Co-IP.

FDX1, SF1, and cJUN levels were significantly elevated in pediatric sepsis patients, especially in those complicated with ALI, and the three genes were positively correlated with each other. In vitro, LPS induced BEAS-2B cell injury, inflammation, and cuproptosis. FDX1 overexpression exacerbated these effects, while its knockdown exerted protective effects. Mechanistically, SF1 directly bound to the FDX1 promoter to activate its transcription. SF1 physically interacted with cJUN, and they synergistically enhanced FDX1 transcription. Knockdown of cJUN abolished SF1-mediated FDX1 upregulation and its pro-cuproptotic effects. In vivo experiments demonstrated that FDX1 knockdown attenuated CLP-induced lung injury, inflammation, and cuproptosis.

SF1, cJUN, and FDX1 may be closely involved in pediatric sepsis-related ALI. The physical interaction between SF1 and cJUN potentially modulates FDX1 transcription, which may contribute to cuproptosis and pediatric sepsis-related ALI progression.

Cardiovascular disease (CVD) remains the leading global cause of mortality, and exercise-based cardiac rehabilitation improves cardiorespiratory fitness and reduces recurrent events. However, center-based rehabilitation is constrained. Telerehabilitation has emerged as a scalable alternative, yet prior systematic reviews have generally bundled exercise training with coequal lifestyle components such as health education, dietary counseling, behavior-change techniques, or psychological support, making it difficult to isolate the cardiometabolic contribution of exercise itself.

This systematic review and meta-analysis quantified the effects of exercise-based telerehabilitation, with exercise as the core therapeutic component, on peak oxygen uptake (VO₂ peak), systolic blood pressure, and diastolic blood pressure in adults with CVD, and examined 5 digital-health dimensions as potential moderators.

Following PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-2020) and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, PubMed, Cochrane Library, Web of Science, Embase, and MEDLINE were searched from inception to March 20, 2026, supplemented by trial registry searches and forward and backward citation searching. Randomized controlled trials comparing exercise-based telerehabilitation with usual care in adults with CVD were eligible. Risk of bias was assessed with the Cochrane RoB 2 tool (Cochrane Risk of Bias Tool version 2). Random-effects meta-analyses used the Hartung-Knapp-Sidik-Jonkman approach: between-study variance (τ²) was estimated by the Sidik-Jonkman method, and CIs were computed with the Knapp-Hartung adjustment. Prespecified meta-regression and subgroup analyses examined 5 digital-health dimensions: telemedicine modality, guidance type, technology platform, intervention duration, and intervention composition. Certainty of evidence was rated using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation).

Thirteen randomized controlled trials (n=958) were included. Exercise-based telerehabilitation significantly improved VO₂ peak (mean difference [MD]=2.58 mL/kg/min, 95% CI 1.16 to 4.00, t₉=4.10, P=.003; 95% prediction interval -1.28 to 6.44; I²=74.45%). The prediction interval crossed 0, indicating that the average effect may not be reproduced in every clinical setting. No significant pooled effect was observed for systolic blood pressure (mean difference -1.80 mm Hg, 95% CI -7.42 to 3.81, P=.42) or diastolic blood pressure (mean difference -2.00 mm Hg, 95% CI -4.76 to 0.75, P=.11). Meta-regression and subgroup analyses did not identify any moderator as a significant source of heterogeneity (all Omnibus P>.05), although smartphone or mHealth (mobile health) delivery and professional-led guidance produced larger and more homogeneous VO₂ peak gains. Possible small-study effects for VO₂ peak were detected (Egger test, P=.03). GRADE certainty was very low across all outcomes.

Exercise-based telerehabilitation probably improves cardiorespiratory fitness in adults with CVD but provides no convincing evidence of an antihypertensive effect. Telerehabilitation should be considered a patient-centered alternative for individuals unable to access center-based rehabilitation, rather than a uniformly equivalent substitute. Component-isolated trials and hypertensive cohort studies with standardized digital-health reporting are needed.

Population pharmacokinetic (PopPK) models have been developed to characterize rivaroxaban exposure; however, their transferability across different clinical populations remains uncertain. This study aimed to externally evaluate published rivaroxaban PopPK models in older Chinese patients with nonvalvular atrial fibrillation (NVAF) and assess whether Bayesian forecasting could improve individual concentration prediction.

Six published rivaroxaban PopPK models were evaluated using an independent cohort from the RIVA-GAP study. Predictive performance was assessed using prediction error metrics reflecting bias, precision, and prediction coverage, together with normalized prediction distribution error (NPDE) diagnostics. Bayesian forecasting was performed using paired steady-state trough-peak concentrations to evaluate changes in individual peak concentration prediction.

A total of 135 patients with 257 rivaroxaban concentration observations were included for external validation, and 122 patients with paired trough-peak samples were included for Bayesian forecasting. Predictive performance varied substantially among the six models, and none consistently met predefined acceptance criteria. Model A showed comparatively lower prediction bias among the evaluated models but still demonstrated limited precision (MDPE 33.64%, MDAPE 53.72%, F30 31.52%). Bayesian forecasting reduced the MDIPE of Model A from 33.64% to 12.38%, but MAIPE remained 37.33% and IF30 was 41.8%. Similar model-dependent effects were observed across the other models.

Published rivaroxaban PopPK models demonstrated heterogeneous transferability in older Chinese patients with NVAF. Bayesian forecasting using a single trough concentration provided modest and model-dependent improvement in concentration prediction but did not consistently overcome limitations of the underlying models.

Chinese Clinical Trial Registry, ChiCTR2300074934; registered 21 August 2023.

To compare subclinical target-organ damage (TOD) across normotension (NT), white-coat hypertension (WCH), and mild-to-moderate hypertension (HT), and examine the association of 24-h systolic blood pressure (SBP) variability with concurrent TOD in untreated WCH.

This single-center retrospective cross-sectional study included 267 hospitalized participants who underwent ambulatory blood pressure monitoring between 2012 and 2021 (91 NT, 93 WCH, 83 HT). TOD markers were compared across groups. Within WCH, multivariable models assessed 24-h SBP variability in relation to any TOD, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and microalbuminuria (MA), adjusting for age, sex, body mass index, and 24-h mean SBP.

Any TOD occurred in 26.4%, 52.7%, and 71.1% of NT, WCH, and HT participants, respectively (P<0.001). Within WCH, any TOD occurred in 35.5%, 64.5%, and 58.1% across increasing variability tertiles; the unadjusted between-tertile comparison was not statistically significant (P=0.056). Continuous 24-h SBP variability was associated with any TOD (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.05-1.52), LVH (OR 1.30, 95% CI 1.08-1.60), LVMI (β=2.23 g/m², 95% CI 0.33-4.12), and log-transformed MA (β=0.105, 95% CI 0.052-0.157). The area under the receiver operating characteristic curve was 0.613 for the base model and 0.678 after adding 24-h SBP variability, with better overall fit of the extended model (likelihood-ratio P=0.009).

WCH showed an intermediate prevalence of any TOD between NT and mild-to-moderate HT. Within WCH, higher 24-h SBP variability was associated with concurrent TOD after accounting for 24-h mean SBP and basic clinical factors, and may provide Supplementary Information when interpreted alongside mean ambulatory blood pressure. These single-center cross-sectional findings do not establish temporal or causal relationships and require confirmation in prospective multicenter studies.

Fibromyalgia (FM) is a chronic, multifactorial pain syndrome involving widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive dysfunction, significantly reducing the quality of life of patients. FM is classified under MG30.01, representing chronic widespread pain, within the broader classification of chronic primary pain according to the International Classification of Diseases, 11th Revision. FM has a complex, multifactorial pathophysiology involving peripheral and central mechanisms that contribute to its marked clinical heterogeneity. Currently, FM is diagnosed primarily through clinical assessment using widely accepted criteria, such as the American College of Rheumatology criteria, most recently revised in 2016, which evolved from the widely used 2010/2011 diagnostic framework. A thorough differential diagnosis is required to distinguish FM from a wide range of rheumatic, neurological, endocrine, psychiatric, and other medical disorders. FM management requires a multidisciplinary approach. Non-pharmacological interventions, including patient education, exercise (eg, aerobic and resistance training), and psychological therapies, such as cognitive behavioral therapy, are recommended as first-line treatments. Pharmacological therapies, including pregabalin, duloxetine, milnacipran, and cyclobenzaprine, are Food and Drug Administration-approved and provide clinically meaningful benefits to patients with FM. Although tramadol may be considered, the use of other opioids is generally not recommended because of their limited efficacy and potential risks. Despite the availability of current diagnostic criteria and treatment options, achieving a consistent diagnosis and optimal outcomes in patients remains challenging. Therefore, this narrative review aims to provide a concise, updated, and clinically relevant overview of the current evidence regarding the pathogenesis, diagnosis, and multidisciplinary management of FM to improve diagnostic accuracy and support individualized patient management. Furthermore, future directions should prioritize improving diagnostic precision and developing mechanism-based interventions targeting the underlying pathophysiology of FM.

Monounsaturated fatty acids (MUFAs) are dietary and circulating fats that may influence cardiovascular health. However, their causal role in cardiovascular diseases (CVDs) remains unclear due to conflicting observational evidence. This study aimed to determine the causal relationship of high serum MUFAs with the risk of various CVDs using the Mendelian randomization (MR) design.

The summary statistics dataset related to serum MUFAs was used from the published genome-wide association study (GWAS) of European descent in UK Biobank participants (n=114,999). Genetic variants underlying angina, atherosclerotic, ischemic heart disease (IHD), myocardial infarction (MI), and hypertension events were ascertained using a GWAS dataset of 461,880 (case=14,828, control=447,052), 463,010 (case=12,171, control=450,839), 361,194 (case=20,857, control=340,337), 462,933 (case=10,616, control=452,317), and 461,880 (case=124,227, control=337,653) European descent participants from the UK Biobank, respectively. We investigated potential association relationships between MUFAs and these outcomes using generalized summary Mendelian randomization (GSMR) and two-sample Mendelian randomization (TSMR). TSMR was employed to validate associations identified by GSMR. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs).

GSMR results showed that MUFAs were associated with angina (OR=1.007, 95%CI:1.005-1.009; P<0.001), atherosclerotic (OR=1.006, 95%CI:1.004-1.008; P<0.001), IHD (OR=1.006, 95%CI:1.003-1.009; P<0.001), MI (OR=1.003, 95%CI:1.001-1.005; P<0.001), and hypertension (OR=1.003, 95%CI:0.998-1.008; P<0.001). Besides, TSMR results indicated that MUFAs were associated with angina (OR=1.012, 95%CI:1.010-1.015), atherosclerotic (OR=1.009, 95%CI:1.006-1.011; P<0.001), IHD (OR=1.015, 95%CI:1.010-1.019; P<0.001), MI (OR=1.007, 95%CI:1.004-1.009; P<0.001), and hypertension (OR=1.021, 95%CI:1.011-1.031; P<0.001). These findings remained consistent when utilizing different MR methods and sensitivity analyses.

The current MR study indicated that higher levels of MUFAs might be associated with an increased risk of CVD events.Preprint Declaration: A preprint version of this manuscript is available at https://www.medrxiv.org/content/10.1101/2023.09.06.23295142v1.

Poststroke dysphagia is common and adversely affects patient outcomes, yet no standardised tool exists to assess nursing management capacity in this area.

To develop and validate the nursing management capacity in poststroke dysphagia (NMC-PSD) Scale, a self-report instrument measuring nurses' perception of unit-level management capacity.

The 35-item scale was adapted from an existing checklist and refined through two rounds of Delphi consultation (I-CVI = 0.80-1.00; S-CVI/Ave = 0.93) and pilot testing. A cross-sectional survey provided psychometric validation. The scale uses a mixed model: a formative structure dimension (resource inputs jointly constituting capacity) alongside reflective process and outcome dimensions. Reliability was evaluated using Cronbach's α for the reflective dimensions and test-retest ICC for the total scale and the human resources composite.

In 410 nurses from 12 Chinese provinces, the 26-item reflective core showed adequate internal consistency (process α = 0.97; outcome α = 0.95) and test-retest reliability (ICC = 0.98). Bifactor model fit was good: χ²(348) = 699.11, CFI = 0.958, TLI = 0.951, RMSEA = 0.050, SRMR = 0.027. The 26-item reflective core showed dominant unidimensionality (ECV = 0.869, ωH = 0.963) and is recommended as the primary validated metric (range 26-130). Nine formative structural indicators, supported by content validity (S-CVI/Ave = 0.93), are reported separately as descriptive resource inputs. Six specific factors had low independent reliability (ωHS = 0.05-0.19) and serve as conceptual or descriptive groupings only. Mean reflective total score was 54.71 (SD = 18.40); the exploratory weighted index was 207.87 (SD = 66.41).

The NMC-PSD Scale demonstrated acceptable psychometric properties as an individual-level measure of nurse-perceived unit capacity. A bifactor re-specification, developed post hoc within the same sample, revealed a dominant general factor underlying the 26 reflective items. Independent cross-validation is warranted. The 26-item reflective total score is recommended as the primary validated metric; nine formative structural indicators are reported separately as descriptive resource inputs. Subscale profiles serve as conceptual or descriptive item groupings only.

The 26-item reflective total score supports individual-level inference regarding nurses' perceptions of unit management capacity. Organisational-level benchmarking requires further validation of within-unit agreement and aggregation reliability. The nine structural indicators offer descriptive resource profiling, and the exploratory weighted index remains supplementary pending criterion-related validation against objective administrative indicators.

Cerebral small vessel disease (SVD) is a leading cause of stroke, vascular cognitive impairment, and functional decline in older adults. Emerging experimental and translational data implicate glymphatic dysfunction in SVD pathogenesis and in vascular amyloid accumulation. The analysis along the perivascular space (ALPS) index, derived from diffusion tensor imaging (DTI), noninvasively estimates water diffusivity along perivascular pathways and has been proposed as an indirect imaging marker related to glymphatic function. In this study, we aim to determine whether the baseline DTI-ALPS index is associated with baseline SVD burden and subsequent longitudinal changes in SVD markers and amyloid-β deposition in cognitively normal aging. We analyzed 204 cognitively normal participants from the Harvard Aging Brain Study with baseline and follow-up visits separated by 3 years. Primary MRI SVD outcomes were intracranial-volume-normalized white matter hyperintensities (WMH/ICV), and visual SVD ratings (Fazekas, ARWMC, perivascular space, and BOMBS [microbleed scale]). Secondary outcomes included cortical amyloid PET burden (PIB_FS_DVR_FLR). We tested the effects of time, baseline ALPS (z-scored), and the time-ALPS interaction using Bayesian mixed-effects models with subject-specific random intercepts adjusted for baseline age, sex, and education; amyloid models were additionally adjusted for APOE4 status. Continuous outcomes were modeled with Gaussian mixed-effects models, binary outcomes with Bernoulli mixed-effects models, and ordinal outcomes with Bayesian cumulative mixed-effects models. In a sensitivity analysis, ALPS was recalculated after excluding voxels with λ₂/λ₃ > 1.8, and the models were repeated using the crossing-fiber-adjusted index. Posterior means and 95% HDIs were the primary summaries. Multiplicity was controlled using the Benjamini-Hochberg false discovery rate procedure, and the resulting FDR-adjusted two-sided posterior tail-area p-analogues are reported as p_corrected. Over the 3-year follow-up, SVD and amyloid-β burden increased: WMH/ICV (β = 0.096, 95% HDI [0.069, 0.121], p_corrected < 0.001), cortical amyloid-β (β = 0.130, 95% HDI [0.106, 0.152], p_corrected < 0.001), Fazekas (β = 0.320, 95% HDI [0.088, 0.541], p_corrected = 0.010), ARWMC (β = 0.404, 95% HDI [0.165, 0.649], p_corrected = 0.004), basal ganglia (β = 0.318, 95% HDI [0.079, 0.546], p_corrected = 0.010), and centrum semiovale (β = 0.244, 95% HDI [0.026, 0.450], p_corrected = 0.025). PVS scores also increased over time. Higher baseline ALPS was associated with lower Fazekas severity (β = -0.742, 95% HDI [-1.281, -0.201], p_corrected = 0.026) and with attenuated amyloid accumulation over time (β = -0.025, 95% HDI [-0.049, -0.001], p_corrected = 0.039). In a sensitivity analysis excluding voxels with a high likelihood of substantial fiber crossing, the ALPS-by-time interaction for amyloid burden remained significant (β = -0.028, 95% HDI [-0.052, -0.003], p_corrected = 0.022), whereas the baseline association with Fazekas severity was attenuated (β = -0.413, 95% HDI [-0.966, 0.181], p_corrected = 0.751). Higher baseline WMH/ICV was associated with poorer baseline global cognition (PACC5) (β = -0.092, 95% HDI [-0.177, -0.011], p_corrected = 0.036), processing speed (β = -0.116, 95% HDI [-0.223, -0.010], p_corrected = 0.036), and executive function (β = -0.144, 95% HDI [-0.251, -0.029], p_corrected = 0.035). Higher baseline amyloid burden was associated with steeper PACC5 decline (β = -0.065, 95% HDI [-0.096, -0.033], p_corrected < 0.001). In cognitively normal older adults, higher conventional baseline ALPS was associated with lower Fazekas severity, although attenuation after crossing-fiber adjustment indicates that this cross-sectional relationship was sensitive to the microstructural composition of the ALPS regions. In contrast, higher baseline ALPS was associated with slower short-term amyloid-β accumulation, and this longitudinal association remained significant after crossing-fiber adjustment. Greater baseline amyloid burden was associated with more rapid decline in global cognition, whereas higher baseline WMH volume was associated with poorer baseline global cognition, processing speed, and executive function. These findings support ALPS as a candidate noninvasive diffusion marker associated with longitudinal amyloid-related change, while emphasizing the need for further validation of its relationship with SVD burden and its biological specificity.

Ketone body levels are elevated in patients with heart failure (HF). Recently, plasma levels of ketone bodies have been associated with mortality in patients with HF. However, little is known about the biological processes active in patients with high levels of ketone bodies. The objective of this study was to investigate the features and prognosis of patients with HF with elevated β-hydroxybutyrate levels. Furthermore, we aimed to determine the specific biological processes that are active in these patients that may result in elevated levels of β-hydroxybutyrate.

β-hydroxybutyrate concentrations were measured by nuclear magnetic resonance spectroscopy in plasma from 478 patients with HF from the BIOSTAT-CHF cohort. In addition, the concentrations of 1057 circulating proteins were measured by liquid chromatography-mass spectrometry. Differential expression and ingenuity pathway analyses were used to investigate which biological processes are associated with high levels of β-hydroxybutyrate. Cox regression was used to investigate the association of β-hydroxybutyrate with mortality and HF hospitalization. Mediation analysis was conducted to determine how much of the association between β-hydroxybutyrate and outcomes is statistically explained by these processes.

The cohort consisted mostly of male patients (64.2%), with equal proportions of HF with reduced ejection fraction and preserved ejection fraction. Elevated β-hydroxybutyrate levels were independently associated with higher heart rate, lower iron levels, and lower body mass index. Moreover, every doubling of β-hydroxybutyrate was associated with a 36.4% increase in mortality (unadjusted hazard ratio 1.364: 95% confidence interval 1.089-1.707). Even after accounting for known risk factors, the relationship remained highly robust (adjusted hazard ratio 1.389; 95% confidence interval 1.150-1.677). Differential expression and ingenuity pathway analyses revealed that higher β-hydroxybutyrate levels were associated with the upregulation of pathways associated with acute inflammation and cachexia, whereas lipogenic and anabolic pathways were down-regulated. Subsequent multiple mediation analysis showed that 76% of the association between β-hydroxybutyrate and mortality was explained by these pathways.

Elevated β-hydroxybutyrate levels predict mortality in chronic HF, independent of established risk factors. Proteomic analysis links elevated β-hydroxybutyrate to heightened inflammation and catabolism, and these pathways largely mediated the association between β-hydroxybutyrate and mortality. These findings suggest that elevated ketone bodies may reflect underlying metabolic stress in patients at risk of adverse outcome.

Primary nephrotic syndrome (NS) is associated with systemic effects that may impact cardiac function, although several studies have explored left ventricle in children with NS. Few studies investigated right ventricle (RV) in this disease. Therefore, the study aimed to provide a comprehensive evaluation of RV functions in children with primary NS using echocardiography.

A case-control observational study was conducted from January 2022 to August 2024 on 40 primary NS patients with steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS), alongside 40 healthy controls. All participants underwent RV assessments using conventional parameters, tissue Doppler imaging (TDI), two-dimensional speckle-tracking echocardiography (2D STE), and three-dimensional echocardiography (3DE).

Significantly lower s', e' in NS patients compared to controls, especially lower in SRNS compared to SSNS. Significantly higher E/e' and Tei index was detected in the NS group compared to controls (p = < 0.001) and more pronounced in SRNS. RV free wall strain longitudinal strain (RVFWLS) and RV four chamber longitudinal strain (RV4CSL) were significantly reduced in NS group compared to controls. 3D auto RV-derived ejection fraction (EF), TAPSE, stroke volume and septal strain were lower in NS compared to controls(p = < 0.001); however, there are no significant differences between SSNS and SRNS. Significant correlations were detected between some echocardiographic parameters and serum cholesterol, albumin, and creatinine.

Integrative use of variable echocardiographic modalities allows detection of subclinical alterations in RV function in children with primary NS, with more affected parameters in SRNS. Therefore, regular surveillance of RV functions in primary NS should be considered.