Circulating cell-free RNA (cfRNA) has emerged as a promising minimally invasive biomarker capable of capturing transcripts originating from multiple tissues and cell types, but its utility in chronic inflammatory airway diseases remains poorly understood. Equine asthma (EA), a naturally occurring respiratory disease that shares key clinical and immunopathological features with human asthma, provides a valuable comparative model for evaluating plasma cfRNA in this context. We performed transcriptomic profiling of plasma cfRNA from horses with EA and healthy controls and compared these findings with partially matched bronchoalveolar lavage (BAL) and whole-blood (WB) transcriptomes. Differential abundance analysis of plasma cfRNA identified increased abundance of the epithelial alarmin IL33, together with signatures associated with tissue remodeling, cellular stress responses, and immune alterations. Notably, cfRNA from EA horses exhibited reduced B-cell-associated and increased T-cell-associated transcript signatures, a pattern independently supported by differential abundance, co-expression network, and deconvolution analyses. In contrast, similar immune-associated signatures were not evident in the BAL and WB transcriptomes analyzed in this study. Cross-compartment comparisons further demonstrated that plasma cfRNA captured a molecular profile largely distinct from those identified in BAL and WB, while sharing only a small set of differentially abundant transcripts across compartments. Collectively, these findings indicate that plasma cfRNA captures molecular patterns associated with EA that differ from those observed in conventional transcriptomic sampling compartments. These results support the potential utility of plasma cfRNA as a minimally invasive source of biomarkers for characterizing airway disease-associated molecular and immune alterations in both veterinary and comparative asthma research.

Oxidative stress is fundamental to the pathogenesis and progression of allergic rhinitis (AR) during mast cell (MC) degranulation. However, effective therapeutic strategies that target both oxidative stress and the degranulation process remain limited. We developed ultrasmall mPEG (2000)-PE-modified zirconium-doped cerium oxide nanoparticles (PEG-CZ NPs) with broad-spectrum reactive oxygen/nitrogen species (ROS/RNS) scavenging and intrinsic phosphatase-like activity and investigated their prophylactic efficacy in an ovalbumin (OVA)-induced mouse model of AR.

PEG-CZ NPs were synthesized and characterized, and their superoxide dismutase-, catalase-, and phosphatase-like activities were assessed. Antioxidative and MC-stabilizing effects were examined in anti-DNP IgE-sensitized, DNP-HSA-challenged RBL-2H3 cells by measuring intracellular ROS/RNS, β-hexosaminidase (β-HEX) release, and transcriptomic changes. Prophylactic efficacy and biosafety were evaluated in OVA-induced AR mice following intranasal administration of PEG-CZ NPs (2 mg kg^-1).

The PEG-CZ NPs were ultrasmall and well dispersed and exhibited robust multienzyme-like activity, efficiently scavenging ROS (H₂O₂, •OH and O₂ ^•-) and RNS (•NO). At 30 μg mL^-1, the PEG-CZ NPs reduced β-HEX release by 50.1% and the intracellular ROS- and RNS-response fluorescence by 84.4% and 95.3%, respectively, without appreciable cytotoxicity. Transcriptomic analysis revealed the suppression of MAPK signaling. In AR mice, they dose-dependently relieved nasal symptoms (maximally 65.7%/79.4% reduction in sneezing/nasal rubbing), rebalanced Th1/Th2 cytokines (48.7% reduction in IL-4, 20.1% reduction in IL-13, 84.7% elevation in IFN-γ), reduced nasal mucosal ROS levels by 69.9% and alleviated mucosal inflammation. No obvious histopathological abnormalities were observed in the major organs during the 31-day study period.

PEG-CZ NPs alleviated AR by scavenging ROS/RNS and inhibiting MC degranulation. These findings support the use of PEG-CZ nanozymes as a promising prophylactic platform for AR.

SARS-CoV-2 undergoes persistent genomic evolution, yet prevalent circulating variants tend to evolve toward reduced pathogenicity. However, direct comparative pathogenesis data involving contemporary, immune-evasive strains-such as the Omicron EG.5 subvariant (a descendant of the globally dominant XBB lineage)-relative to ancestral strains remain scarce.

To clarify the evolutionary trajectory of viral virulence, we conducted a systematic, head-to-head comparison of the in vivo pathogenicity of three pivotal strains: the ancestral Wild-type (Wuhan lineage), Delta, and the currently circulating Omicron EG.5. We utilized the highly susceptible K18-hACE2 transgenic mouse model to assess disease progression, viral burden, and histopathology.

Despite uniformly progressing to lethality in this model, the strains exhibited a distinct gradient in the kinetics and severity of disease. The Wild-type strain demonstrated the most rapid disease progression, highest viral loads across multiple organs (notably liver, brain, lung, and intestine), and most severe histopathological damage. The Delta variant showed an intermediate phenotype. Strikingly, the Omicron EG.5 variant displayed significantly attenuated pathogenicity, characterized by markedly delayed mortality, milder clinical presentation, and reduced tissue viral burden, yet it retained a capacity for multi-organ infection.

Our study provides direct experimental evidence for a pronounced attenuation in pathogenicity along the evolutionary trajectory from Wild-type through Delta to Omicron EG.5. These findings offer crucial insights for risk assessment of emerging variants and underscore the need for ongoing surveillance.

Immune recovery after withdrawal of long-term immunosuppression may unmask autoimmune disease, but thyroid autoimmunity in patients with failed kidney allografts remains poorly characterized. We report a 29-year-old man with kidney allograft failure who developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after discontinuation of maintenance immunosuppression and subsequently presented with weight loss, tremor, tachycardia, diffuse goiter, and overt thyrotoxicosis. Positive thyrotropin receptor antibodies (TRAb) and diffusely increased radionuclide uptake supported a diagnosis of Graves' disease rather than destructive thyroiditis. His symptoms and thyroid function improved following treatment with methimazole, propranolol, glucocorticoids, and supportive treatment. Extracorporeal blood-purification therapies were used in the setting of persistent tachycardia, dialysis-related blood pressure fluctuations, and systemic inflammation, although their independent contribution could not be determined. Persistently elevated TRAb levels despite low peripheral B-cell counts suggested that circulating B-cell numbers did not reliably reflect humoral autoimmune activity. This case highlights a possible immune reconstitution-associated form of thyroid autoimmunity after immunosuppression withdrawal and emphasizes early recognition and thyroid evaluation following new inflammatory triggers.

Our objective was to describe morphologic features and longitudinal changes observed on high-resolution vessel wall imaging (HR-VWI) in a selected retrospective case series of patients evaluated for suspected inflammatory intracranial vasculopathy.

This retrospective case series included patients who underwent 3T intracranial HR-VWI for suspected inflammatory intracranial vasculopathy. Clinical and imaging data were collected from medical records and imaging archives. Three radiologists reviewed baseline and follow-up examinations for vessel wall enhancement (VWE) pattern and grade, wall thickness, luminal narrowing, arterial distribution, diffusion-restricted lesions, and susceptibility-sensitive findings. Analyses were descriptive and patient-level. Each patient contributed one baseline and one final examination to longitudinal summaries; intermediate scans characterized individual trajectories only.

Nineteen patients were included, and 17 underwent serial HR-VWI. Median age was 46 years (IQR, 35.5-60.0 years), and 11 patients were female. Follow-up HR-VWI was available in 17 patients over a median of 391 days (IQR, 237-1819 days; range, 15-4034 days). VWE was present in all patients, with a purely concentric pattern in 15/19 (78.9%). The middle cerebral and internal carotid arteries were involved in 17/19 and 13/19 patients, respectively. Among the 17 patients with paired examinations, VWE grade decreased in 13 patients (76.5%) and remained stable in four patients (23.5%), with the median decreasing from 3.0 to 1.0. Maximum wall thickness decreased in 16 patients and remained stable in one, with the median changing from 2.0 mm to 1.4 mm.

In this selected retrospective case series of patients evaluated for suspected inflammatory intracranial vasculopathy, 3T HR-VWI commonly demonstrated concentric VWE and provided descriptive longitudinal information regarding enhancement evolution. These findings should not be interpreted as evidence of diagnostic performance.

Background/Objectives: Myocardial perfusion PET/CT, e.g., using Rb-82, enables the measurement of absolute myocardial blood flow (MBF) and, hence, the blood flow reserve, which plays a crucial role in the diagnosis of coronary artery disease. However, the values might depend on the observer's analysis and, thus, depend on the observer's experience. We investigated the inter-observer reliability of MBF measurements in Rb-82-PET/CT. Methods: Thirty consecutive patients who underwent Rb-82-PET/CT for suspected myocardial ischemia were analyzed. Stress conditions were simulated using 400 µg Regadenoson. MBF was measured using Corridor 4DM software. Myocardial flow reserve (MFR) is the ratio of absolute flow measurements under stress and rest conditions. Four different physicians with different levels of experience (two senior physicians and two residents) measured the MBF. The experience of the two residents was one year of experience and no previous experience, respectively. Intraclass correlation coefficients (ICC) were calculated for MBF and MFR in the three main vascular territories as well as in the whole left ventricle. Additionally, the left ventricular ejection fraction (EF) was determined. Results: The evaluation of MBF showed an excellent correlation between all observers, indicated by a low inter-observer variability. Comparing the two different levels of experience, senior physicians showed a slightly higher accordance in MBF assessment (ICC ranging from 0.9 to 0.98) than the residents (ICC ranging from 0.86 to 0.94). The MFR calculations showed a slightly lower reliability due to the accumulation of variability in rest and stress measurements (ICC between 0.78 and 0.81), still indicating a good reliability. The EF calculations also showed a good reliability among the different observers (ICC 0.83). Conclusions: Measurement of MBF, MFR and EF in Rb-82-PET/CT is highly robust with a very low inter-observer variability. A slightly higher inter-observer reliability was found for more experienced physicians.

Post-stroke spasticity may interfere with function and rehabilitation and contribute to pain, contracture, care burden, and disability. Botulinum toxin type A is an established focal treatment for post-stroke spasticity, but it is often introduced in the chronic phase, when persistent involuntary muscle overactivity may coexist with secondary musculoskeletal complications. This opinion paper critically examines whether early treatment with botulinum toxin should be considered a myth or an emerging clinical reality. Current evidence from meta-analyses, randomized trials, observational cohorts, and pooled analyses was reviewed with particular attention to treatment timing, treatment triggers, functional outcomes, and prevention of secondary complications. The literature supports the clinical usefulness of earlier treatment in appropriately selected patients, particularly for reducing focal involuntary muscle overactivity and resistance to passive movement, delaying symptomatic progression, slowing contracture development, and reducing pain-related complications. However, a consistent additional effect on active motor recovery has not been demonstrated, and evidence for participation and long-term functional independence remains less definitive. Moreover, "early" is heterogeneously defined across studies, ranging from the first weeks to the first year after stroke. We therefore propose moving from a rigid time-based concept of "early" treatment toward timely, target- and goal-guided intervention, integrating botulinum toxin with rehabilitation when a clinically relevant and modifiable focal neural treatment target emerges. To operationalize this concept, we propose a pragmatic set of clinical variables including the neural treatment target, its clinical impact and trajectory, passive musculoskeletal status, pain and care burden, motor recovery context, rehabilitation goals, and patient priorities.

Post-stroke spasticity involves both neural and non-neural mechanisms, including structural alterations of muscles and surrounding fascia. Although botulinum toxin type A (BoNT-A) is widely used to treat focal spasticity, its effects on fascial tissue remain unclear. This retrospective observational study investigated longitudinal changes in fascial thickness after BoNT-A injection using ultrasonography. Thirty-seven patients with post-stroke spasticity were included. Fascial thickness was measured at baseline, 3 weeks, and 3 months after treatment in the injected muscle regions. Clinical outcomes were assessed using the Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and Brunnstrom stages. Repeated-measures analysis demonstrated significant reductions in fascial thickness across all evaluated regions. Pairwise comparisons showed significant decreases from baseline to week 3 and month 3, whereas continued reductions between week 3 and month 3 were observed only in the flexor digitorum superficialis fascia, the flexor digitorum superficialis-flexor digitorum profundus interfascial layer, and the deep brachialis fascia. MAS scores and upper extremity Fugl-Meyer scores improved significantly, whereas Brunnstrom stages remained unchanged. These findings suggest that the therapeutic effects of BoNT-A may extend beyond neural inhibition to include fascial remodeling. Ultrasonographic assessment of fascial thickness may represent a potential imaging biomarker for monitoring structural treatment responses in post-stroke spasticity.

Atrial fibrillation (AF) is associated with atrial remodelling, hemodynamic stress, and complex cardiopulmonary interactions. While natriuretic peptides and echocardiographic abnormalities are established markers of AF-related substrate, the contribution of spirometry changes, as a landmark of pulmonary impairment, remains less clearly defined. This study evaluated whether AF is associated with an integrated cardiopulmonary profile characterized by altered spirometry, increased NT-proBNP, and conventional echocardiographic markers of left atrial structure and function.

We performed a retrospective, single-center observational study based on an existing clinical database of adult patients referred for 24 h 12-lead Holter ECG monitoring because of palpitations and/or chest pain. None of the included patients had a previously documented diagnosis of atrial fibrillation before Holter monitoring. Because a single 24 h Holter recording cannot establish spontaneous termination or long-term temporal pattern with certainty, AF documented for the first time during this recording is referred to throughout as "newly detected AF" rather than "paroxysmal AF". During Holter monitoring, no ECG changes suggestive of myocardial ischemia were detected. From 536 records of patients without previously known AF who underwent 24 h 12-lead Holter ECG monitoring for palpitations and/or chest pain, 164 patients were retained for the main comparison, including 48 with newly detected paroxysmal AF and 116 without AF. Demographic, biochemical, spirometric, and echocardiographic variables were analyzed. The main respiratory parameters were forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF). NT-proBNP was the primary biomarker, while conventional left atrial structural and functional variables were used for echocardiographic assessment.

NT-proBNP was markedly higher in the AF group (684.5 vs. 62.3 pg/mL, p = 0.001), even when accounting for confounders like age, CKD, or CPD, showing by far the largest between-group difference among the biomarkers assessed (formal discrimination statistics such as ROC/AUC were not computed). The exploratory inflammatory markers assessed (hs-CRP, neutrophil/lymphocyte ratio, homocysteine) showed only modest, non-significant differences. Conventional echocardiographic parameters did not differ significantly between groups. In the strict complete-case comparison, spirometric indices did not reach statistical significance; however, preliminary project-level analysis showed lower FVC, FEV1, and PEF in AF patients, but without supporting the COPD diagnosis, and exploratory correlations suggested a relationship between spirometric performance and left atrial function.

In this cohort, AF was most strongly associated with NT-proBNP, while the respiratory signal was weaker but directionally consistent with a broader cardiopulmonary phenotype. These findings do not support spirometry or NT-proBNP as stand-alone diagnostic tools for AF. However, when interpreted alongside traditional AF risk factors and symptoms, elevated NT-proBNP with concordant spirometric impairment may represent a hypothesis-generating additive signal supporting longer or repeated rhythm monitoring beyond 24 h in selected patients with suspected AF; this additive value was not formally tested against clinical models alone and requires prospective confirmation.

In-hospital cardiac arrest (IHCA) remains associated with poor survival, while the contribution of arrest etiology and early physiological markers to outcome remains incompletely defined. We examined associations between clinical, neurological, metabolic, and etiological factors and sustained return of spontaneous circulation (ROSC) lasting >20 min, 28-day survival, and 60-day mortality.

This retrospective single-center cohort included 134 adults with confirmed IHCA requiring cardiopulmonary resuscitation at a tertiary university hospital with advanced transplant care between 2011 and 2015. Sustained ROSC and 28-day survival were analyzed using parsimonious Firth penalized logistic regression models, and 60-day mortality using Cox proportional hazards regression. Selected neurological and biomarker analyses were considered exploratory.

Sustained ROSC was achieved in 91 patients (67.9%), 33 (24.6%) survived to day 28, and 30 (22.4%) survived to day 60. Initial non-shockable rhythm was associated with lower odds of sustained ROSC (aOR 0.26, 95% CI 0.09-0.69) and 28-day survival (aOR 0.27, 95% CI 0.10-0.68), and with higher 60-day mortality (aHR 1.96, 95% CI 1.25-3.08). The presence of a potentially reversible cause was associated with more favorable outcomes, whereas active hematologic malignancy was associated with higher 60-day mortality (aHR 1.89, 95% CI 1.15-3.10). Exploratory analyses also showed associations of initially dilated pupils with lower 28-day survival and higher lactate with 60-day mortality. Among patients who survived beyond 24 h, higher BNP was associated with subsequent mortality.

Non-shockable rhythm and the presence of a potentially reversible cause were consistently associated with outcomes following IHCA, while active hematologic malignancy was associated with poorer longer-term survival. Exploratory findings from lactate, initial pupillary assessment, and BNP may provide complementary prognostic information, although the BNP analysis was limited to patients who survived beyond 24 h. These findings require confirmation in contemporary multicenter cohorts and do not establish validated clinical prediction tools.