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PubMed2026

Safe and Stable Germline Transmission of MSTN Mutations in Cattle.

With the global population expected to reach 10 billion by 2050, sustainable livestock production is critical. Gene editing of the myostatin (MSTN) gene represents a promising strategy to enhance muscle growth in cattle. In this study, MSTN-mutated founder (F0) cows were used to generate F1 offspring via ovum pick-up, in vitro fertilization, and embryo transfer. Four F1 calves were born, all confirmed to be heterozygous for the MSTN mutation. Long-term monitoring showed normal growth and no visible health abnormalities. Whole-genome sequencing identified SNPs, INDELs, and structural variants, most with minimal predicted functional effects. Proteomic profiling of Longissimus dorsi muscle quantified 2947 proteins, revealing only subtle expression differences between MSTN-mutated and wild-type cattle. These results demonstrate stable inheritance and confirm that MSTN editing does not disrupt genome integrity or protein expression. Overall, our findings support the safety and utility of MSTN gene editing to improve livestock productivity for future food security.

Animals↗

PubMed2026

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log₁₀(P) ≥ 6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C > T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals↗

PubMed2026

Comprehensive source-risk assessment of organophosphate esters in surface water of the Dianchi Lake Basin, Yunnan, China.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, have been increasingly detected in aquatic environments. However, investigations of their distribution in high-altitude plateau lakes remain scarce. Identifying and quantifying the sources and associated risks of OPEs are crucial for subsequent water environment management. In this study, an integrated source-risk analysis approach was employed by combining the Positive Matrix Factorization (PMF) model, the Geodetector (GD) model, and risk quotient (RQ). Analysis of 14 OPEs in surface waters of the Dianchi Lake Basin (DLB) revealed 12 detectable compounds, with total OPEs concentrations (ΣOPEs) ranging from not detected (ND)-64.6 ng/L during the wet season and ND-35.8 ng/L during the dry season. Elevated ΣOPEs were primarily observed at inflow sites in the northern part of the lake and in urban rivers. Source apportionment indicated four major contributing sources: agricultural films containing flame-retardant and plasticizer additives, traffic-related particulate emissions, releases from household and personal care products, and industrial production and applications of flame retardants in plastics, electronics, and related products (the predominant source). The ecological impact caused by OPEs ranges from no risk to low risk, with tris(2-chloroethyl) phosphate emitted from industrial source being the primary driver of potential environmental risk. These findings highlight the necessity of prioritizing industrial sources in future management strategies. Overall, this study provides a methodological framework for source apportionment and risk assessment of OPEs and offers scientific evidence to support environmental management of OPEs in the DLB.

Environmental Monitoring↗

PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗

PubMed2026

The spatial and temporal distribution of Staphylococcus aureus along a tropical Hawaiian watershed.

Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.

Staphylococcus aureus↗

PubMed2026

Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value. METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool. RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181. CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.

Humans↗

PubMed2026

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2‒102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans↗

PubMed2026

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans↗

PubMed2026

Divergent evolutionary strategies in spider venoms: A comparative proteomic profiling of four sympatric species from Yunnan.

Spider venoms comprise complex cocktails of bioactive molecules evolved for predation and defense, representing a valuable resource for biological research and pharmaceutical discovery. In this study, we performed a systematic analysis of venom gland extracts from four common spider species indigenous to Yunnan, China: Agelena limbata, Hippasa lycosina, Lycosa grahami, and Sinopoda pengi. Using an integrated transcriptomic and proteomic targeted profiling approach, we successfully annotated 141 distinct toxins. Comparative analysis revealed significant interspecific heterogeneity, suggesting distinct evolutionary trajectories and "weapon system economics." Both A. limbata and L. grahami exhibited a "peptide-dominant" profile anchored by neurotoxic peptides and isomerases, optimized for rapid chemical paralysis. In contrast, S. pengi displayed a distinct "protein-dominant" signature enriched with high-molecular-weight enzymes and CAP superfamily proteins, likely functioning to facilitate tissue degradation and toxin diffusion. Occupying an intermediate position, H. lycosina demonstrated a hybrid composition. These findings suggest that although these species share the same geographical range, their venom systems have undergone divergent evolutionary adaptations driven by specific ecological niches and hunting strategies. This study represents the first systematic proteomic characterization of these venom components, providing a valuable reservoir of molecular candidates while highlighting the bioinformatic nuances of analyzing whole-gland homogenates.

Animals↗

PubMed2026

Free polyphenols and multi-omics traits underlying antioxidant variation across Paeonia lactiflora leaf cultivars.

Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397 ng/mg, respectively, compared with 0.012 and 0.002 ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.

Antioxidants↗

PubMed2026

Deimplementation of inappropriate feeding practices in early care and education: a Hybrid Type 3 cluster-randomized trial.

BACKGROUND: The science of deimplementation-reducing harmful or ineffective practices-has focused almost exclusively on clinical prescribing, with no studies conducted in community or educational settings. Early care and education (ECE) settings offer a strategic venue for shaping eating behaviors, with children consuming up to 500 meals annually in these environments. However, ECE educators routinely use feeding practices that undermine self-regulation, including pressuring children to eat, rushing mealtimes, and offering food as reward. These practices contribute to food aversions, diminished self-regulation, and obesity risk. METHODS: We will conduct a Hybrid Type 3 cluster-randomized trial evaluating a co-designed deimplementation strategy package (WISE Words) across 88 ECE sites in Arkansas and Louisiana. Sites will be randomized 1:1 to WISE Words or usual practice, with usual practice sites receiving the intervention after two years (waitlist design). WISE Words includes six strategies: dynamic training using improvisation methods, peer learning collaboratives with goal setting, external facilitation, audit and feedback, environmental reminders, and tailored educational materials. The primary outcome is de-adoption of inappropriate feeding practices measured via direct mealtime observation (Table Talk). Secondary outcomes include adoption of evidence-based practices, acceptability, appropriateness, and sustainability at 12- and 24-months post-intervention. Child outcomes include Body Mass Index, skin carotenoid levels (Veggie Meter) willingness to try new foods (observed) and food neophobia (teacher and caregiver report). An explanatory sequential mixed methods design will test mechanisms of change derived from the Implementation Trust Building Theory of Change examining whether trust mediates strategy effects on outcomes. DISCUSSION: This trial extends deimplementation science into community settings by targeting culturally embedded behavioral practices rather than clinical prescribing behaviors. Results will inform approaches to shifting entrenched practices in ECE and similar settings while testing trust as a deimplementation mechanism. Sustainability assessments will address a notable gap, as few studies have examined whether deimplementation effects persist. TRIAL REGISTRATION: NCT07101321, July 20, 2025.

Humans↗

PubMed2026

Psychiatric mental health nurse practitioner outcomes after completion of a 1-year postgraduate fellowship.

Psychiatric mental health nurse practitioners (PMHNPs) are an essential and growing part of the health care workforce, especially in community settings. To address PMHNPs' increasing presence in community psychiatry, a 1-year postgraduate PMHNP fellowship in community psychiatry was developed with the goals of enhancing clinical competency and employment retention in underserved public sector settings. Data on 5 cohorts and 31 fellows are presented in this article. PMHNP fellows, preceptors, didactics, and clinical sites were evaluated across several time points including baseline and 6 and 12 months. The program has graduated 100% of fellows with largely positive feedback. Fellows reported significant improvements in competency across the domains of 1) assessment and diagnosis, 2) treatment, and 3) professionalism and leadership. These items were substantiated by clinical preceptors' ratings of fellows' clinical skills from 6-month and 12-month time points. Relatedly, clinical sites, preceptors, and didactics were all rated highly by fellows. After the program, 90.3% of graduates remained working in the public sector including correctional settings, community clinics, and safety net hospitals.

Community psychiatry↗

PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗

PubMed2026

Distal versus proximal radial access for diagnostic cerebral angiography: comparative outcomes and learning curve analysis.

BACKGROUND AND PURPOSE: Distal transradial access (dTRA) is an alternative to proximal transradial access (pTRA) for neuroangiography, but comparative real-world data and evidence on its early learning curve remain limited. We compared procedural performance and access-site complications between dTRA and pTRA and evaluated the early learning curve of dTRA. METHODS: We retrospectively analyzed 470 diagnostic cerebral angiography procedures, representing 421 unique patients, performed via radial access at a single center between January 2025 and February 2026, including 237 dTRA and 233 pTRA procedures. Baseline characteristics, including age, sex, body mass index (BMI) category, aortic arch type, and antiplatelet/anticoagulant use, procedural performance, and clinically assessed access-site events were compared between groups. Radial artery occlusion (RAO) was assessed by postoperative bedside pulse examination and confirmed with Doppler ultrasound when clinical findings were uncertain. Multivariable logistic regression was used to evaluate predictors of RAO, persistent bleeding or repeated compression, hand edema, and a composite access-site event endpoint. Because repeated procedures occurred in a subset of patients and event counts were limited, first-procedure sensitivity analysis and analyses of infrequent outcomes were interpreted cautiously. The dTRA learning process was assessed in the first 100 dTRA cases performed by a single operator using multivariable regression, cumulative sum (CUSUM) analysis, segmented trend analysis, and phase-based comparisons. RESULTS: Baseline characteristics were comparable between groups, including age, male sex, BMI category, aortic arch type, and antiplatelet/anticoagulant use. Compared with pTRA, dTRA was associated with more puncture attempts (3.0 [2.0-4.0] vs 2.0 [1.0-3.0], P < 0.001), longer puncture time (2.0 [1.0-5.0] vs 2.0 [1.0-3.0] min, P = 0.003), lower first-pass success (19.4% vs 35.2%, P < 0.001), and a higher crossover rate (11.4% vs 6.0%, P = 0.037). However, dTRA was associated with a lower clinically assessed RAO rate (2.5% vs 7.7%, P = 0.011). On multivariable analysis, pTRA was independently associated with higher odds of RAO (OR 3.27, 95% CI 1.26-8.49, P = 0.015) and the composite access-site event endpoint (OR 3.12, 95% CI 1.55-6.28, P = 0.001). Similar findings were observed in a sensitivity analysis restricted to the first procedure per patient. In the first 100 dTRA cases, cumulative dTRA experience was independently associated with shorter total procedure time (beta = -0.074 min/case, P = 0.009), while CUSUM and moving-average analyses suggested that the major learning effect occurred within approximately the first 10-15 cases. CONCLUSIONS: In this retrospective single-operator cohort, dTRA was associated with lower clinically assessed RAO than pTRA despite greater access difficulty. The early learning effect was mainly reflected in shorter total procedure time. These findings support the feasibility of dTRA but should be interpreted cautiously given the study's observational design and limited anatomical data.

Humans↗

PubMed2026

Suppression of AAV-Delivered Transgene Expression Using Artificial MicroRNAs Delivered by an Alternative AAV Serotype.

Adeno-associated virus (AAV) gene transfer vectors mediate long-term expression in nondividing cells, an advantage for treating chronic disorders. However, current platforms lack a way to selectively shut down transgene expression if adverse effects arise. To create an "off switch," we hypothesized that incorporating unique artificial microRNA (amiRNA) target sequences into an AAV expression cassette would allow subsequent suppression of transgene expression using a second AAV vector encoding the cognate amiRNA. We introduced 22-nt sequences absent from human and mouse transcriptomes into the 3' untranslated region (UTR) of a therapeutic AAV cassette. To identify optimal amiRNAs, two tandem copies of each amiRNA were cloned into the 3'UTR of an mCherry reporter gene. In vitro assessment of six amiRNA/target pairs using a dual luciferase assay identified four amiRNAs that efficiently suppressed reporter expression. Cells cotransfected with target site 3 (TS3) and amiRNA-T3B showed the greatest reduction in luciferase activity (80%, p < 0.0001) and were selected for further study. The "off-switch" system was then evaluated using an AAV5 therapeutic vector expressing a recombinant humanized anti-IgE monoclonal antibody (AAV5-TBG-anti-IgE-TS3), designed for long-term suppression of allergen-induced reactions. Co-transfection of HEK293T cells with anti-IgE-TS3 and amiRNA-T3B significantly reduced anti-IgE mRNA and protein levels relative to a control amiRNA (p < 0.0001). In vivo testing in Balb/c mice (n = 5) involved intravenous administration of AAV5-anti-IgE-TS3 (3.2 × 1010 gc), followed 4 weeks later by an AAVrh.10 amiRNA vector (AAVrh.10-TBG-amiRNA-T3B; 1 × 1011 gc). Control mice receiving only the therapeutic vector expressed 18.4 ± 13.8 µg/mL serum anti-IgE at 10 weeks. In contrast, mice receiving the amiRNA "off" vector showed marked suppression of anti-IgE (0.3 ± 0.15 µg/mL, p < 0.0001). These findings provide proof-of-concept that AAV-delivered amiRNAs can selectively switch off transgene expression, offering a strategy to improve the safety of AAV-mediated gene therapies.

Dependovirus↗

PubMed2026

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗

PubMed2026

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans↗

PubMed2026

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15 years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24 h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24 h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6 ml kg -1 of levobupivacaine 2.5 mg ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg kg -1 in the TAP and infiltration groups, respectively ( P  = 0.95). FLACC scale values did not significantly differ between the two groups ( P  = 0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test = 0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans↗