Publications by authors named "Soul J"

Background: Neonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone.

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  • Emerging research links age-related musculoskeletal diseases, particularly osteoarthritis (OA), to developmental factors, highlighting the importance of DNA methylation in OA risk.
  • A study quantified DNA methylation across approximately 700,000 individual CpGs in developing human chondrocytes, revealing significant changes in 3% of CpGs and over 8,200 differentially methylated regions during development.
  • Findings indicate that specific OA genetic variants align with methylation changes, suggesting that understanding these developmental processes could significantly influence future genetic-based therapies for OA.
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  • * Results showed that 65% of the children had abnormal sleep scores, and around 27% screened positive for sleep-disordered breathing, with higher occurrences in those with cerebral palsy or epilepsy.
  • * The findings suggest a significant relationship between sleep issues and parental anxiety/depression, emphasizing the importance of early screening and treatment for sleep disorders to potentially improve outcomes for these children.
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Changes in chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so recognition of the regulative processes during chondrogenesis can lead to a better understanding of OA. microRNAs (miRNAs) are key regulators of gene expression in chondrocytes/OA, and we have used a combined experimental, bioinformatic, and systems biology approach to explore the multiple miRNA-mRNA interactions that regulate chondrogenesis. A longitudinal chondrogenesis bioinformatic analysis identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators.

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  • * In studies with miR-324-null mice, researchers found that these mice had increased bone density and thickness, reduced lipid content in bone marrow, and higher bone formation rates, indicating a strong connection between miR-324 and bone maintenance.
  • * It was revealed that miR-324-5p targets key regulators in bone cells, such as Pin1 and Runx2, which influence the balance between bone formation and resorption, highlighting the potential for miR-324-related therapies in treating bone diseases.
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Background: Parents of neonates with seizures report persistent symptoms of depression, anxiety, and posttraumatic stress. We aimed to characterize the parent experience of caring for children impacted by neonatal seizures, including longitudinal assessment across childhood.

Methods: This prospective, observational, multicenter study was conducted at Neonatal Seizure Registry (NSR) sites in partnership with the NSR Parent Advisory Panel.

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  • - The study compares two animal models of post-traumatic osteoarthritis (PTOA) using C57Bl6 mice: a non-surgical ACL rupture and a surgical destabilization of the medial meniscus, finding they produce similar pathological changes.
  • - Transcriptome profiling and gene ontology analysis revealed that both models share enriched pathways, primarily focusing on anabolic processes.
  • - The research highlights the significance of microRNA miR-199-5p, linking its inhibition in human chondrocytes to changes similar to those seen in both OA patients and the animal models, further establishing the ACL model as a useful tool in PTOA research.
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  • Serine proteinase inhibitors (serpins) are proteins that play important roles in various biological processes, including blood coagulation and extracellular matrix remodeling.
  • This study reveals that SERPINA3, a specific serpin, is crucial for the differentiation of mesenchymal stem cells into chondrocytes during early cartilage development, showing increased expression during this process.
  • Silencing SERPINA3 impairs cartilage formation and reduces levels of SOX9, a master regulator of chondrogenesis, indicating that SERPINA3 is essential for proper chondrocyte differentiation through the regulation of SOX9.
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  • The study aimed to assess how different international clinical sites manage therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) and identify areas for standardization.
  • An electronic survey was conducted, gathering responses from 105 sites, primarily from high-income regions, revealing varying practices in eligibility criteria, use of electroencephalography, and sedation methods.
  • The findings indicated significant regional differences in TH management, suggesting that future guidelines should take into account the availability of resources globally.
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Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4 and CD8 T lymphocytes from patients with psoriasis and AD.

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The epigenome, including the methylation of cytosine bases at CG dinucleotides, is intrinsically linked to transcriptional regulation. The tight regulation of gene expression during skeletal development is essential, with ~1/500 individuals born with skeletal abnormalities. Furthermore, increasing evidence is emerging to link age-associated complex genetic musculoskeletal diseases, including osteoarthritis (OA), to developmental factors including joint shape.

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  • Advances in perinatal and neonatal care have improved the survival rates of preterm infants, shifting the focus to enhancing long-term neurological outcomes.
  • Current therapies like antenatal steroids show short-term benefits, but there's little evidence for long-term neurodevelopmental improvement, necessitating further research into effective neuroprotective strategies.
  • Promising treatments under investigation include multipotential stem cells and anti-inflammatory therapies, while immediate care methods that nurture brain health in NICUs are crucial for fostering neuroplasticity.
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Objective: Among neonates with acute symptomatic seizures, we evaluated whether inability to take full feeds at time of hospital discharge from neonatal seizure admission is associated with worse neurodevelopmental outcomes, after adjusting for relevant clinical variables.

Methods: This prospective, 9-center study of the assessed characteristics of infants with seizures including: evidence of brainstem injury on MRI, mode of feeding upon discharge, and developmental outcomes at 12, 18, and 24 months. Inability to take oral feeds was identified through review of medical records.

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Background: Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures.

Methods: Neonatal seizure burden was calculated from continuous video-EEG data.

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Variation in mesenchymal stromal cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs are attributed to secretion of biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome remains largely unknown.

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Background: Neonatal encephalopathy (NE) continues to be a significant risk for death and disability. To address this risk, regional guidelines were developed with the support of a malpractice insurance patient safety organization. A NE registry was also established to include 14 centers representing around 50% of deliveries in the state of Massachusetts.

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Background: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO's potential as a diagnostic for HIE.

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Background: Limited data exist regarding seizure burden, electroencephalogram (EEG) background, and associated outcomes in neonates with acute intracranial infections.

Methods: This secondary analysis was from a prospective, multicenter study of neonates enrolled in the Neonatal Seizure Registry with seizures due to intracranial infection. Sites used continuous EEG monitoring per American Clinical Neurophysiology Society guidelines.

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Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children.

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Mild isolated fetal ventriculomegaly (iFVM) is the most common abnormality of the fetal central nervous system. It is characterized by enlargement of one or both of the lateral ventricles (defined as ventricular width greater than 10 mm, but less than 12 mm). Despite its high prevalence, the pathophysiology of iFVM during fetal brain development and the neurobiological substrate beyond ventricular enlargement remain unexplored.

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Background: Children with a history of acute provoked neonatal seizures are at high risk for disability, often requiring developmental services. The coronavirus disease 2019 (COVID-19) pandemic has led to widespread changes in how health care is delivered. Our objective was to determine the magnitude of service interruption of among children born between October 2014 and December 2017 and enrolled in the Neonatal Seizure Registry (NSR), a nine-center collaborative of pediatric centers in the United States.

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Background: Neurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD.

Methods: Fetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3).

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