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The inhibitory effect of M2 macrophage-derived exosomes on gefitinib resistant lung adenocarcinoma cells through the MIF/TIMP1/CD74 axis
Family Screening in Relatives at Risk for Plakophilin-2–Associated Arrhythmogenic Right Ventricular Cardiomyopathy
BACKGROUND: Penetrance and risk of ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are increasingly recognized as being genotype specific. Therefore, genotype-informed family screening protocols may lead to safer and more personalized recommendations than the current one-size-fits-all screening recommendations. We aimed to develop a safe, evidence-based plakophilin-2 ( PKP2 )–specific longitudinal screening algorithm. METHODS: We included 295 relatives (41% male; age 30.9 years [18.0–47.7 years]) with a pathogenic or likely pathogenic PKP2 variant from 145 families. Phenotype was ascertained with ECG, Holter monitoring, and cardiac imaging and classified by the 2010 Task Force Criteria. VA was defined as a composite of sudden cardiac arrest or death, spontaneous sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter defibrillator intervention. We performed Cox regression to determine predictors of ARVC development and multistate modeling to assess the probability of ARVC development and occurrence of VA. RESULTS: At baseline, 110 relatives (37%) had definite ARVC. During 8.5 years (4.2–12.9 years) of follow-up, 62 of 185 relatives (34%) without definite ARVC at baseline progressed to definite ARVC diagnosis, and 35 of 295 of all relatives (12%) had VA. VAs occurred only in relatives who previously fulfilled definite ARVC diagnosis. Relatives with borderline ARVC (fulfillment of one minor criterion plus the major family history criterion) progressed 5 times faster in the multistate model to definite ARVC diagnosis and compared with genotype-positive/phenotype-negative (G+/P−) relatives (ie, major family history criterion alone). Relatives 20 to 40 years of age had increased risk for developing definite ARVC (hazard ratio, 2.23; P =0.012) compared with those ≥40 years of age. New Task Force Criteria fulfillment most commonly occurred first on ECGs, followed by Holter monitoring and cardiac imaging. Consequently, 3 risk profiles were identified, and appropriate screening protocols were derived: relatives with borderline ARVC (annual ECG and Holter monitoring; complete evaluation [ie, ECGs, Holter monitoring, and imaging] every 2 years), younger (<40 years of age) or symptomatic G+/P− relatives (every 2 years an ECG and Holter monitoring; complete evaluation every 4 years), and older (≥40 years of age) and asymptomatic G+/P− relatives (complete evaluation every 5 years). CONCLUSIONS: An evidence-based longitudinal screening algorithm that integrates age, symptoms, and baseline clinical phenotype may improve patient care and improve efficiency of clinical resource allocation.
Phytochemical profiling and network pharmacology-based prediction of Pelargonium graveolens essential oil in the context of Guillain-Barré syndrome
Abstract Guillain-Barré syndrome (GBS) is a rare autoimmune disorder with limited treatment options. This study investigates the chemical composition of Pelargonium graveolens essential oil and explores its potential interaction with GBS-related molecular targets using in-silico tools. Essential oil was analyzed using GC–MS. Identified components were subjected to network pharmacology analysis and molecular docking to assess binding affinities with GBS-relevant proteins, particularly TNF-α. Thirty compounds were identified, with citronellol (26.74%) and geraniol (20.28%) as major components. Comparative phytochemical analysis showed consistency with global P. graveolens chemotypes. Docking results suggest high binding affinity of citronellyl and geranyl derivatives toward TNF-α. These findings support further investigation of P. graveolens oil as a potential modulator of inflammatory pathways in GBS.
Aortic Aneurysm Risk and the Somatic <i>JAK2</i> <sup> <i>V617F</i> </sup> Mutation: Insights From a Multicenter, Population-Based Cardiovascular Screening Study
BACKGROUND: The somatic JAK2 V617F sequence variation, a key driver of myeloproliferative neoplasms, has been associated with increased risk of aortic aneurysms. This study aimed to explore associations between the JAK2 V617F variant allele frequency (VAF) and ascending, descending, and abdominal aortic aneurysms. METHODS: In the DANCAVAS I and II trials (Danish Cardiovascular Screening), 15 000 individuals underwent cardiovascular risk assessments including blood samples and noncontrast ECG-gated computed tomography scans. In this cross-sectional substudy, individuals with screening-detected aortic aneurysms (≥45 mm ascending, ≥35 mm descending, or ≥30 mm abdominal), random aneurysm-free male controls, and all women (only included during the DANCAVAS I pilot study) were tested for the JAK2 V617F sequence variation. RESULTS: A total of 8056 individuals (90.9% men, mean age 68±4 years) were tested for the JAK2 V617F sequence variation, which presented an overall prevalence of 7.1%. Ascending, descending, and abdominal aneurysm prevalences were 6.6%, 2.9%, and 6.8%, respectively. In JAK2 V617F -negative participants (n=7486), JAK2 V617F -positive participants with VAF <1% (n=491), and JAK2 V617F -positive participants with VAF ≥1% (n=79), ascending aortic aneurysms were observed in 6.4%, 9.0%, and 16.5%, respectively ( P <0.001). No significant differences were observed across sequence variation groups for descending and abdominal aneurysms. Among JAK2 V617F -positive individuals, the median VAF was higher in those with ascending aneurysm (9.5%; interquartile range, 3.0–40.0) than in controls (4.4%; interquartile range, 1.8–20.0; P =0.021). Ascending aortic diameter correlated modestly with VAF (Spearman ρ=0.10; P =0.026). No significant correlations were observed for descending or abdominal diameters. For ascending aneurysms, JAK2 V617F VAF <1% and ≥1% presented adjusted odds ratios of 1.4 (95% CI, 1.01–2.0; P =0.045) and 2.7 (95% CI, 1.5–5.1; P =0.002), respectively, compared with JAK2 V617F -negative controls. For each doubling in VAF, the risk for ascending aneurysm increased by 11% ( P adjusted =0.013). The JAK2 V617F sequence variation was not significantly associated with descending or abdominal aneurysms after adjusting for covariates and using these VAF thresholds. CONCLUSIONS: In a study population of primarily men 60 to 74 years of age, the somatic JAK2 V617F sequence variation was strongly and independently associated with ascending aortic aneurysms, presenting a positive correlation between aneurysm size and JAK2 V617F VAF. No convincing associations were observed for descending or abdominal aneurysms. Screening patients with larger ascending aortic aneurysms for the JAK2 V617F sequence variation, and vice versa, screening JAK2 V617F -positve individuals presenting higher VAFs for ascending aneurysms, may be clinically appropriate.
Transfer learning driven fake news detection and classification using large language models
Two Sides of a Coin: Safety Versus Harm of the ACC/AHA Perioperative Guideline Class 1 Level C-LD Recommendation for SGLT Discontinuation
Publisher Correction: Graphical model analysis of subjective well-being and various factors in Japanese adults from the Iwaki cross-sectional study
Author Correction: Bmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP
Reduced risk of lymphedema after immediate breast reconstruction in breast cancer: a retrospective nationwide study
Machine learning enables legal risk assessment in internet healthcare using HIPAA data
Integrin β5 interacts with G3BP1 through activating FAK/Src signaling pathway to promote gastric carcinogenesis
A novel cuproptosis-related genes nomogram on the prognosis and immune microenvironment of breast invasive carcinoma
Author Correction: Clinical significance and effect of lncRNA HOXA11-AS in NSCLC: a study based on bioinformatics, in vitro and in vivo verification
Exploring the nucleus accumbens circuit and oxytocin therapy in a Sapap3 knockout mouse model of trichotillomania
Innovative approach to IOL-bag complex fixation with Siepser’s scleral sliding knots in pseudoexfoliation syndrome
Federated learning with enhanced cryptographic security for vehicular cyber-physical systems
A novel blockchain technology-based supply chain coordination considering classified after-sales services of electronic products
Correction: Predictors of fatigue improvement in multimodal, multimodal-aerobic and aerobic exercise intervention studies in breast cancer survivors with cancer-related fatigue
Room-temperature ethylene glycol sensor based on cuprous oxide/MXene films
Abstract This study demonstrates a high-performance room-temperature ethylene glycol (EG) gas sensor using Cu2O/MXene bilayer films on quartz crystal microbalance (QCM) substrates, addressing critical needs for industrial safety and environmental monitoring. The fabricated sensors were systematically characterized by XRD, FTIR, and FESEM, revealing that the Cu2O/MXene bilayer configuration achieved exceptional performance with an ultra-low detection limit of 381 ppb, high sensitivity of 22.8 Hz/ppm, and excellent selectivity compared to individual Cu2O, MXene, or their mixture films. The enhanced sensing capability originates from synergistic effects between p-type Cu2O and conductive MXene, forming a Schottky junction that facilitates charge transfer and promotes EG adsorption through combined physisorption mechanisms involving hydrogen bonding with MXene’s functional groups (OH, O, F) and interactions with oxygen species on Cu2O nanoparticles. At 72 ppm EG concentration, the bilayer sensor exhibited 12.6-fold, 3.6-fold, and 2.34-fold higher response than pure Cu2O, MXene alone, and their mixture film, respectively. While humidity tests showed a moderate ~ 15% response reduction at 60% RH, the Cu2O/MXene bilayer maintained robust performance, establishing it as a cost-effective and reliable room-temperature sensing platform suitable for next-generation gas detection applications in challenging environments.