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PubMed2026

Improving survival in Duchenne muscular dystrophy across eras: a systematic review and cumulative meta-analysis.

BACKGROUND: Duchenne muscular dystrophy (DMD) was historically associated with death in the late teens or early twenties, mainly from respiratory failure. Survival has improved substantially with home mechanical ventilation (HMV) and multidisciplinary care, although variability remains. This study evaluated temporal trends in survival in DMD and the impact of HMV. METHODS: A study-level cumulative meta-analysis (PROSPERO CRD420251163011) of studies reporting survival outcomes in patients with DMD was conducted (PubMed 1977 to 13 October 2025). Pooled estimates of median survival were calculated, and random-effects meta-analyses with predefined subgroups (HMV and study period) were performed, alongside meta-regressions. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: 53 studies (median follow-up 8 years), comprising more than 13,000 patients, of whom 60% received HMV, were included. Median survival differed substantially between ventilated (29 years, 95%CI 27 to 31) and non-ventilated (19 years, 95%CI 18 to 20) patients. Survival improved progressively over time in both groups. Glucocorticoid therapy was not associated with improved survival (p=0.45), whereas treatment with heart failure medications, including renin-angiotensin system inhibitors (p=0.002) and β-blockers (p=0.02), was associated with longer survival. The predominance of mortality shifted from respiratory to cardiac causes, while enhanced cardiac management was associated with a growing contribution of other causes of death. CONCLUSION: Survival in DMD has increased substantially over time, with median survival now approaching the third decade of life among ventilated patients. The growing contribution of cardiac and other non-respiratory causes of death highlights the importance of long-term multidisciplinary and early cardioprotective intervention. STUDY REGISTRATION: The meta-analysis and systematic review have been registered on PROSPERO (CRD420251163011).

Humans↗

PubMed2026

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist = max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median Δ -21.0 ms; 95% CI -33.9 to -18.6; p < 0.001). Signed VED16 did not change significantly (median Δ 0.4 ms; p = 1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median Δ -5.2 ms; p = 0.070), whereas dist decreased significantly (median Δ -0.7 ms; 95% CI -14.4 to 0.0; p = 0.015). The proportion of patients within the normal dyssynchrony band (|VED16| ≤ 20 ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r = -0.45, p = 0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans↗

PubMed2026

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans↗

PubMed2026

Epithelial regeneration in the gastrointestinal tract.

The gastrointestinal tract possesses a remarkable regenerative capacity to maintain tissue homeostasis against various injuries. However, the intestine and stomach exhibit distinct regenerative strategies. In the intestine, damage to Lgr5-positive (Lgr5+) stem cells induces cellular plasticity and the emergence of transient Revival stem cells (RevSCs), a process critically dependent on YAP/TAZ signaling. Conversely, the stomach utilizes paligenosis, where quiescent p57-positive (p57+) mature chief cells act as reserve stem cells, dedifferentiating to restore damaged tissue. Although the cellular origins differ, both organs appear to share some common regenerative features, including transient activation of pro-proliferative programs such as YAP/TAZ signaling. In contrast, whether Retinoic Acid (RA) signaling also serves as a conserved mechanism for regenerative resolution in the stomach remains to be determined. In this review, we discuss the cellular and molecular mechanisms governing regeneration in these two organs. This comparative analysis provides a framework for future research.

Regeneration↗

PubMed2026

An automated geometric modeling framework in GATE for the design and optimization of high-sensitivity converging-beam SPECT collimators.

Objective.The trade-off between detection sensitivity and spatial resolution is a fundamental challenge in designing organ-dedicated Single-photon emission computed tomography (SPECT) collimators. While converging-hole geometries offer a solution, their optimization is often hindered by the lack of flexible computational tools capable of modeling large-scale, non-parallel hole arrays. This study aims to develop an automated geometric modeling framework to facilitate the design and evaluation of complex converging- and diverging-hole collimators within standard Monte Carlo environments.Approach.We developed a specialized modeling framework by implementing custom C++ classes and a vector-based alignment algorithm within GATE. This platform enables automated, orientation-consistent construction of large-scale converging arrays not natively supported by standard implementations. A high-sensitivity pure cone-beam collimator (CBC) was designed using this framework. The evaluation used hot-rod, disc, and Jaszczak phantoms for physical characterization, while XCAT and dedicated brain models were employed for clinical tasks, including cardiac, brain perfusion, and DaTscan SPECT simulations.Main results.The CBC achieved a nearly fourfold sensitivity increase compared to a conventional low-energy high-resolution parallel-hole collimator at a 20 cm radius of rotation, while maintaining comparable spatial resolution. Despite a 52.3% field of view reduction, the CBC yielded a 2.2-fold noise reduction (CV: 11.7% vs 25.9%) and mitigated partial volume effects via geometric magnification. XCAT and brain phantom simulations confirmed enhanced anatomical definition and contrast recovery in cardiac, perfusion, and DaTscan tasks.Significance.This work provides an efficient computational tool for rapid design space exploration of advanced collimator geometries. The results demonstrate that the proposed CBC design offers a significant sensitivity advantage, making it highly suitable for high-performance, small-volume clinical applications such as brain and cardiac molecular imaging.

Tomography, Emission-Computed, Single-Photon↗

PubMed2026

Impact of renal dysfunction on immediate versus staged revascularization of non-culprit lesions in patients with ST segment elevation myocardial infarction: a pre-specified subgroup analysis of the randomized MULTISTARS AMI trial.

BACKGROUND: Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). METHODS: In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2. Patients with an eGFR < 30 ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1 year. RESULTS: In MULTISTARS AMI, 108 (13%) of 832 patients had renal dysfunction. The primary endpoint occurred more frequently in patients with renal dysfunction (19.4% vs. 11.2%, unadjusted HR 1.82, 95% CI 1.13-2.94), primarily driven by higher rates of death. Among patients with renal dysfunction, the rates of the primary end point were 14.5% and 24.5% in the immediate and staged PCI groups (unadjusted HR 0.55, 95% CI 0.23-1.33). There was no interaction between renal dysfunction and the randomized treatment assignment with respect to the primary end point (adjusted HR 1.30, 95% CI 0.8-2.20, pint 0.82). The occurrence of acute renal insufficiency was statistically similar in patients with renal dysfunction who underwent immediate and staged PCI (10.9% vs. 18.9%, unadjusted HR 0.61, 95% CI 0.22-1.72, pint 0.09). Renal dysfunction at baseline emerged as a strong risk factor for the development of acute renal insufficiency (adjusted HR 5.0, 95% CI 2.30-10.70, p < 0.01). CONCLUSIONS: Outcomes with immediate compared to staged multivessel PCI did not appear significantly altered by the presence of renal dysfunction at baseline. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275).

Humans↗

PubMed2026

Lipid-mediated activation of BLT2 promotes membrane repair to prevent cell death.

Various pathogenic microorganisms produce toxins that create pores in cell membranes, causing cell damage and disrupting the host epithelial barrier. Recently, we reported that mice lacking the G protein-coupled receptor leukotriene B4 receptor 2 (BLT2), which is expressed in vascular endothelial and alveolar epithelial cells, are highly susceptible to pneumolysin (PLY), a pneumococci-generated toxin. Although we clarified the protective roles of BLT2 in vascular endothelial cells, those in alveolar epithelial cells have not been elucidated. Here, we report that lipid mediator 12-hydroxyheptadecatrienoic acid (12-HHT), which is produced by membrane-damaged epithelial cells, prevents cell death by promoting membrane repair through BLT2. BLT2 promoted the release of PLY-bound plasma membranes as extracellular vesicles in a sphingomyelinase-dependent manner. Additionally, BLT2 activated Rac1 and subsequent actin polymerization, leading to resistance to cell death. Furthermore, inhibition of 12-HHT production by aspirin and treatment with a BLT2 antagonist abolished the protective effect of BLT2. These findings provide a new therapeutic strategy for bacterial infection.

Receptors, Leukotriene B4↗

PubMed2026

Effects of essential amino acid supplementation on musculotendinous recovery following eccentric plantar flexor exercise: a randomized controlled trial.

BACKGROUND: Exercise-induced muscle damage (EIMD) resulting from eccentric contractions leads to transient impairments in muscle function. Essential amino acids (EAAs) stimulate muscle protein synthesis and may support recovery following damaging exercise. However, limited research has examined the effects of EAAs on muscle function following eccentric plantar flexor exercise. The purpose of this study was to examine the effects of EAA supplementation on indirect markers of muscle and musculotendinous recovery following EIMD. METHODS: Thirty-six recreationally active males (age: 21.2 ± 2.7 years) were randomly assigned to an EAA group (10 g of EAAs), placebo (10 g of maltodextrin), or control (no supplementation). Supplements were consumed 30 minutes before and immediately after an eccentric plantar flexor protocol (4 × 50 repetitions followed by one set to failure) and during the 72 hours recovery period. Indirect markers of muscle damage were assessed pre-exercise, immediately post-exercise, and 24, 48, and 72 hours post-exercise, consisting of perceived soreness (NPRS), pain pressure threshold (PPT), calf muscle thickness and Achilles tendon thickness (ultrasound), and calf circumference. RESULTS: The eccentric protocol elicited responses consistent with EIMD, including increased soreness (p < 0.001), increased calf muscle thickness and circumference (p < 0.001), and reduced PPT (p = 0.018). EAA supplementation attenuated soreness at 24 hours compared with placebo. Calf muscle thickness increased following exercise in both groups; however, swelling returned to baseline by 72 hours in the EAA group but remained elevated in placebo (Condition × Time, p < 0.001). Achilles tendon thickness decreased immediately post-exercise (p = 0.005) but was not influenced by supplementation. CONCLUSIONS: EAA supplementation modestly reduced soreness and was associated with faster recovery of muscle swelling but did not influence tendon morphology within 72 hours.

Humans↗

PubMed2026

Self-healing materials for food packaging: Design principles, activation mechanisms and implications for food safety.

Self-healing materials (SHMs), originally developed to restore mechanical integrity, have recently attracted growing interest in food packaging. By autonomously repairing physical damage, SHMs help preserve packaging integrity, barrier performance, food safety, and shelf-life during storage and transportation. This review summarizes recent advances in the design principles, activation mechanisms, material systems and food packaging applications of SHMs. Key healing strategies, including microencapsulation, dynamic covalent bond exchange, reversible non-covalent interactions and responsiveness to external stimuli such as temperature, pH, and humidity, are discussed. Representative material systems, including biopolymer-based films, hydrogels, nanocomposites, and stimuli-responsive polymers are evaluated with respect to their relevance to packaging animal-derived foods, fruits, and vegetables. Performance evaluation methods, sustainability implications, and food-contact safety concerns are addressed. Despite promising healing efficiency and mechanical resilience, challenges remain regarding production cost, food-grade safety, migration risks, trigger compatibility and stability under fluctuating environmental conditions. Future research should focus on scalable manufacturing, standardized evaluation protocols, repeated damage-healing safety assessment, regulatory compliance, and integration with intelligent packaging technologies.

Food Packaging↗

PubMed2026

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗

PubMed2026

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans↗

PubMed2026

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P = .03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P = .005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P = .15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P = .54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans↗

PubMed2026

Unraveling the Clinical Spectrum of DNASE1L3 Deficiency: Insights from Case Series and Systematic Literature Review.

BACKGROUND: DNASE1L3 deficiency is a rare monogenic cause of lupus and lupus-like autoimmunity resulting from impaired extracellular DNA clearance and sustained immune activation. Although most reported patients present with early-onset systemic lupus erythematosus (SLE), emerging evidence suggests broader phenotypic variability, including vasculitic and overlap manifestations. Whether these presentations represent distinct clinical entities or a continuum of DNASE1L3-associated immune dysregulation remains unclear. We aimed to define the clinical spectrum of DNASE1L3 deficiency and examine the relationship between recurrent pathogenic variants and disease severity. METHODS: We conducted a combined pediatric case series and systematic literature review. Four children with genetically confirmed biallelic DNASE1L3 variants followed at a tertiary pediatric rheumatology centre were retrospectively analysed for clinical, immunological, genetic, treatment, and outcome data. In parallel, a systematic search of PubMed/MEDLINE, Scopus, and Web of Science identified previously reported patients with confirmed biallelic pathogenic or likely pathogenic DNASE1L3 variants and extractable patient-level clinical data. To facilitate cross-case comparison, we applied an exploratory three-tier descriptive framework reflecting increasing disease severity: vasculitic or organ-limited disease (G1), systemic lupus or overlap phenotypes without irreversible organ damage (G2), and severe systemic organ-damaging disease (G3). The assigned grades were descriptive rather than permanent categories, as some patients may meet the criteria for a higher grade if broader systemic manifestations or irreversible organ damage develop during follow-up. FINDINGS: Fifteen reports provided extractable patient-level data, corresponding to 45 unique previously reported patients after accounting for known or probable overlapping reports. Combined with four patients from our centre, the analysis included 49 genetically confirmed individuals. SLE-dominant disease was the most frequent phenotype (27 [60%] of 45), followed by hypocomplementaemic urticarial vasculitis/HUVS-dominant disease (10 [22.2%]) and overlap phenotypes (8 [17.8%]). Renal involvement was reported in 30 (66.7%) of 45 patients, and disease onset occurred by age 3 years in 20 (44.4%). Persistent hypocomplementemia affecting C3 and C4 was frequently reported across the spectrum. Recurrent DNASE1L3 variants were observed across multiple phenotypic and severity grades. Variants such as p.Asn191Ser and p.Thr97Ilefs*2 occurred in patients spanning organ-limited vasculitic disease, lupus overlap phenotypes, and severe multisystem lupus with major organ involvement. CONCLUSION: DNASE1L3 deficiency was associated with a broad clinical spectrum of immune-mediated disease rather than a single clinicopathological entity. The occurrence of identical pathogenic variants across distinct phenotypic and severity states argues against a simple genotype-phenotype model and suggests that additional modifiers influence disease expression.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand↗

PubMed2026

Long-term heat exposure reshapes muscle molecular regulation and enhances thermal tolerance in Clarias fuscus.

Rapid fluctuations in water temperature driven by global warming have become a major abiotic stressor affecting muscle function in teleost fish. This study examined the effects of long-term thermal conditions on heat tolerance in Clarias fuscus. Fish were maintained for 90 days at either a normal temperature group (NT, 26 °C) or a high-temperature group (HT, 34 °C). Subsequently, muscle histology, and transcriptomic profiles were observed following acute high-temperature exposure (34 °C) and after temperature recovery (26 °C). Histological analysis showed that fish from the NT under acute high-temperature stress exhibited severe muscle damage (atrophy, myofilament disruption, and myolysis), whereas fish from the HT displayed markedly reduced lesions. RNA-seq profiling revealed 5769 differentially expressed genes (DEGs) in the NT and 3292 DEGs in the HT following acute temperature challenges. Functional enrichment indicated that, in the HT, modulation of key cell cycle regulators (e.g., ccna, ccnb, cdk1, cdk2) contributed to alleviating muscle damage caused by temperature fluctuations. In the NT, genes associated with ribosome biogenesis (e.g., nop56, riok2, riok1) were up-regulated and then down-regulated during temperature fluctuation, whereas p53 in the cell cycle pathway showed the opposite expression pattern. These findings demonstrate long-term heat exposure reshapes molecular expression and regulatory mechanisms in the muscle of C. fuscus, thereby enhancing thermal tolerance and adaptability, and providing a theoretical basis for breeding heat-resistant, high-quality aquaculture strains.

Animals↗

PubMed2026

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets + vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans↗

PubMed2025

UV-based homogeneous disinfection process for removal of antibiotic resistance genes: Efficiency, mechanisms and influencing factors.

The proliferation and dissemination of antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to global public health. Ultraviolet-driven homogeneous advanced oxidation processes (UV-AOPs) represent a prospective suite of technologies for the efficient removal of ARGs. This review critically assesses recent advances in the application of UV-AOPs, specifically UV/hydrogen peroxide (UV/H2O2), UV/peracetic acid (UV/PAA), UV/persulfate (UV/PS), and UV/chlorine (UV/Cl), for the elimination of extracellular ARGs and intracellular ARGs. The underlying mechanisms involve direct ultraviolet-induced DNA damage, including pyrimidine dimer formation and strand breakage, as well as oxidation mediated by radicals such as hydroxyl radicals, sulfate radicals, carbon-centered radicals, and reactive chlorine species. The relative contribution of radical and non-radical pathways is strongly influenced by water chemistry and process conditions. We further expound on the critical operational and environmental factors governing ARG removal kinetics, including UV wavelength and fluence, oxidant type and dosage, ARG sequence characteristics, pH, ubiquitous anions, and dissolved organic matter, which collectively affect radical generation, quenching, and reaction microenvironments. Notably, for i-ARGs, UV-AOPs facilitate degradation not only through direct radical attack but also by disrupting cellular integrity and permeabilizing membranes, thereby enhancing the exposure of genetic materials to oxidative and photolytic damage. This review synthesizes current understanding to provide a mechanistic basis for the design and optimization of UV-AOP systems, highlighting their potential as effective barriers against the dissemination of antibiotic resistance in water reuse and purification scenarios.

Disinfection↗