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We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18 months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains: intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles: a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD.

Prematurity is a prototype of biological risk that could affect the late neurocognitive outcome; however, the condition itself remains a non-specific marker. This longitudinal 6-year study aimed to evaluate the prognostic role of neonatal spectral EEG in premature infants without neurological complications. The study cohort was 26 children born 23–34 gestational ages; all neonates underwent multichannel EEG recordings at 35 weeks post-conception. EEG data were transformed into the frequency domain and divided into delta (0.5–4 Hz), theta (5–7 Hz), alpha (8–13 Hz), and beta (14–20 Hz) frequency bands. At 6 years, a neuropsychological and behavioral evaluation was performed. Correlations between spectral bands and neuropsychological assessments were performed with a conservative and robust Bayesian correlation model using weakly informative priors. The correlation of neuropsychological tasks to spectral frequency bands highlighted a significant association with visual and auditory attention tests. The performance on the same tests appears to be mainly impaired.Conclusions: We found that spectral EEG frequencies are independent predictors of performance in attention tasks. We hypothesized that spectral EEG might reflect early circuitries’ imbalance in the reticular ascending system and cumulative effect on ongoing development, pointing to the importance of early prognostic instruments.What is Known:• Prematurity is a non-specific marker of late neurocognitive risk.• Precise prognostic instruments are lacking, mostly in patients with low-grade conditions.What is New:• Longitudinal long-term studies are scarce but crucial for the inferential attributive process.• Spectral EEG frequencies are independent predictors of performance in attention tasks.

Innovative clinical trial designs, such as adaptive and Bayesian methodologies, have gained traction as solutions to the challenges of traditional trials, including their high costs and complex regulations. When they adhere to relevant ethical and regulatory requirements, these designs can improve efficiency, flexibility, and ethical standards. However, their application outside of oncology, particularly in fields such as neuroscience and rare diseases, remains underexplored. We analyzed data from ClinicalTrials.gov for interventional trials registered between 2005 and 2024. The trials were classified as innovative or traditional using a keyword-based algorithm. Therapeutic areas were identified using a large language model (LLM), with classification accuracy evaluated using a random sample of 2,000 trials. Of the 348,818 trials, 5827 were classified as innovative, with prevalence in neuroscience and rare diseases. These designs were predominantly observed in early-phase trials and pediatric research, with limited representation in elderly-focused or sex-specific studies. Innovative trial adoption has grown since 2011, spurred by regulatory advancements and increased funding from scientific networks and the National Institutes of Health. Survival analysis revealed that innovative trials tend to remain active for longer than traditional trials; however, this trend varies across different medical disciplines. LLM demonstrated a classification accuracy of 94.6% (95%CI = 93.6%-95.5%), supporting its utility for trial categorization. The rise in innovative clinical trial designs reflects a shift toward addressing complex challenges in neuroscience, rare diseases, and other therapeutic areas. Although these designs show promise in improving trial efficiency and patient outcomes, their success depends on rigorous planning and adherence to regulatory standards. Advancing LLM-based tools can further optimize clinical trial monitoring by tailoring research in trial settings and therapeutic fields.

Background: Obesity is a major public health issue in developed countries, primarily managed through dietary interventions and physical activity. Food portion sizes influence the estimation of energy intake, particularly through bites, of which characteristics remain insufficiently defined. This study investigates the variability in bite energy content. Methods: This observational study was conducted over 14 months. Thirteen types of packaged food were provided to 30 Italian healthy volunteers (mean age 26.8 ± 8.5 years) in a semi-naturalistic dietary feeding setting. Participants’ anthropometric measurements were recorded. A total of 1850 bites were weighed and 420 bites were assessed for volume and energy content. Results: Bite volume and mass explained bite energy content at different rates. The most influential anthropometric feature was waist circumference. Gender modified the association between waist circumference and bite characteristics; males showed increased bite volume, mass, and energy content as waist circumference increased, whereas females showed little or no association. Age was inversely associated with bite volume and mass, with younger participants having larger bites. Gender significantly influenced average bite size, with females showing lower values than males. The use of a fork was associated with higher bite volume, mass, and energy compared to a spoon. Food eaten with bare hands had lower mass but higher energy content compared to food eaten with a spoon. The variability in bite energy was considerably greater per bite than per gram, reflecting the combined influence of food texture, bite size, and cutlery used. Conclusions: Bite energy variability, influenced by intrinsic factors (gender, age, waist circumference) and extrinsic factors (cutlery, food texture), significantly impacts portion size effect. Future bite counters should consider these elements for accurate dietary assessment.

Background Chorioamnionitis is associated with preterm delivery and morbidities; its role in lung disease is controversial. The aim of this study is to assess the effect of chorioamnionitis on metabolite and lipid profiles of epithelial lining fluid in preterm newborns with respiratory distress syndrome (RDS). Methods The study involved 30 newborns with RDS, born from mothers with or without histological chorioamnionitis (HCA): HCA+, N  = 10; HCA−, N  = 20. Patients had a gestational age ≤30 weeks; the groups were matched for age and birth weights. Tracheal aspirates were collected within 24 h after birth and analyzed using liquid chromatography/mass spectrometry-based untargeted lipidomics. Results According to Mann–Whitney U tests, 570 metabolite features had statistically significantly higher or lower concentrations ( p  < 0.05) in tracheal aspirates of HCA+ compared to HCA−, and 241 metabolite features were putatively annotated and classified. The most relevant changes involved higher levels of glycerophospholipids (fold change 2.42–17.69) and sphingolipids, with lower concentration of all annotated sphingomyelins in HCA+ (fold change 0.01–0.50). Conclusions Untargeted lipidomics of tracheal aspirates suggested the production of lipid mediators in the context of an ongoing inflammatory status in HCA+ babies. However, the effect of chorioamnionitis on epithelial lining fluid composition deserves further investigations on a larger group of infants. Impact Our lipidomics investigation on tracheal aspirates of preterm newborns at birth suggested that exposure to maternal histological chorioamnionitis may cause changes in epithelial lining fluid composition. This is the first description of epithelial lining fluid lipidomic profiles in preterm infants with and without exposition to chorioamnionitis. These results could provide novel link between placental membrane inflammation and newborns’ respiratory outcome.

Introduction: Cochlear implants (CI) have been developed to enable satisfying verbal communication, while music perception has remained in the background in both the research and technological development, thus making CI users dissatisfied by the experience of listening to music. Indications for clinicians to test and train music abilities are at a preliminary stage compared to the existing and well-established hearing and speech rehabilitation programs. The main aim of the present study was to test the utility of the application of two different patient reporting outcome (PRO) measures in a group of CI users. A secondary objective was to identify items capable of driving the indication and design specific music rehabilitation programs for CI patients. Materials and Methods: A consecutive series of 73 CI patients referred to the Audiology Unit, University of Padova, was enrolled from November 2021 to May 2022 and evaluated with the audiological battery test and PRO measures: Musica e Qualità della Vita (MUSQUAV) and Nijmegen Cochlear Implant Questionnaire (NCIQ) Italian version. Results: The reliability analysis showed good consistency between the different PRO measures (Cronbach’s alpha = 0.873). After accounting for the epidemiological and clinical variables, the PRO measures showed a correlation with audiological outcomes in only one case (rho = −0.304; adj. p = 0.039) for NCIQ-T with the CI-pure tone average. A willingness for musical rehabilitation was present in 63% of patients (Rehab Factor, mean value of 0.791 ± 0.675). Conclusions: We support the role of the application of MUSQUAV and NCIQ to improve the clinical and audiological evaluation of CI patients. Moreover, we proposed a derivative item, called the rehab factor, which could be used in clinical practice and future studies to clarify the indication and priority of specific music rehabilitation programs.

Ryanodine receptor 1-related myopathies (RYR1-RM) are caused by RYR1 gene variants and comprise a wide spectrum of histopathological manifestations. Here, we focus on patients carrying RYR1 variants and muscle histopathology consistent with central core disease (CCD) or multi-minicore disease (MmD). RNA-sequencing analyses of skeletal muscle biopsies obtained from both CCD and MmD patients and from healthy controls were performed to better understand the molecular pathways activated by RYR1 variants. Our analyses revealed that, beyond the well-established role of RYR1 in calcium homeostasis, broader cellular pathways are implicated. In CCD, differentially expressed genes were enriched for pathways related to oxidative stress response, SMAD signalling, and apoptosis, consistent with the role of intracellular calcium dysregulation in promoting mitochondrial dysfunction and cell death. In contrast, MmD patients exhibited enrichment of pathways related to immune activation. This was corroborated by the upregulation of GTPase-regulating genes and the down-regulation of transcriptional repressors such as ZFP36 and ATN1. When considering all RYR1-RM patients collectively, Wnt signalling, immune-related pathways, and oxidative phosphorylation emerged as shared enriched pathways, indicating possible convergent mechanisms across histopathological phenotypes. Our study suggests that complex gene regulation driven by RYR1 variants may be a unifying feature in CCD and MmD, offering new insight into potential therapeutic targets.

The term progressive pulmonary fibrosis (PPF) refers to a specific disorder that becomes worse despite optimal treatment. The pathogenic explanation of this progressive worsening is still to be found. In this study, we explored whether any histological, molecular, radiological, or clinical features could predict a progressive phenotype in patients with fibrotic interstitial lung diseases. Two hundred and fifteen patients with PPF other than idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated ILD (CTD-ILD) were followed in our ILD clinic between January 2016 and May 2023. Based on tissue block availability, 48 patients were definitively enrolled. Progression was defined according to the most recent guidelines. Clinical, radiological, and functional data were also collected retrospectively and correlated with tissue morphological and molecular cytokine profiles. Fifteen patients were classified as progressors (PPF) and 33 as non-progressors (nPPF) with similar age at diagnosis and gender. PPF showed a higher prevalence of traction bronchiectasis (80% vs. 27%; p=<0.001) at CT scan and lower functional parameters [FVC: 2.42 L vs. 3.37 L; p=0.004; TLC: 3.83 L vs. 4.65 L; p=0.027] at diagnosis. Lung specimens revealed a significant overexpression of IL9 in the PPF compared to the nPPF group (p=0.049). Boruta algorithm analysis showed that lymphoid aggregates and traction bronchiectasis at diagnosis are the most important variables in determining the PPF status. The present results increase the understanding of the pathological mechanisms of PPF, offering potential avenues for improved prognostication and therapeutic intervention.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by irreversible scarring of the distal lung. IPF is best described by its histopathological pattern of usual interstitial pneumonia (UIP), characterized by spatial heterogeneity with alternating interstitial fibrosis and areas of normal lung, and temporal heterogeneity of fibrosis characterized by scattered fibroblastic foci (FF), dense acellular collagen and honeycomb changes. FF, comprising aggregated fibroblasts/myofibroblasts surrounded by metaplastic epithelial cells (EC), are the cardinal pathological lesion and their presence strongly correlates with disease progression and mortality. We hypothesized that the EC/FF sandwich from patients with UIP/IPF has a distinct molecular signature which could offer new insights into the crosstalk of these two crucial actors in the disease. Laser capture microdissection with RNAseq was used to investigate the transcriptome of the EC/FF sandwich from IPF patients versus controls (primary spontaneous pneumothorax). Differentially expressed gene analysis identified 23 up-regulated genes mainly related to epithelial dysfunction. Gene ontology analysis highlighted the activation of different pathways, mainly related to EC, immune response and programmed cell death. This study provides novel insights into the IPF pathogenetic pathways and suggests that targeting some of these up-regulated pathways (particularly those related to secreto-protein/mucin dysfunction) may be beneficial in IPF. Further studies in a larger number of lung samples, ideally from patients with early and advanced disease, are needed to validate these findings.

COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1β and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.