Publications by authors named "Connelly J"

Objectives: Long-term kidney outcomes after extracorporeal membrane oxygenation (ECMO) are little quantified and understood. We aimed to describe the frequency of kidney dysfunction screening during follow-up and the prevalence of long-term kidney disease.

Design: Retrospective cohort of pediatric ECMO patients with estimated glomerular filtration rate (eGFR) (mL/min/1.

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Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

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Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume.

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A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy. Pre- and post-contrast T-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans.

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Background And Objectives: Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess.

Methods: 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess.

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Article Synopsis
  • Glioblastoma multiforme (GBM) is the most aggressive brain tumor but rarely spreads outside the central nervous system, with only 0.4% of cases showing metastasis, possibly influenced by genetic mutations.
  • A systematic review analyzed 357 studies and 211 patients, revealing that 36.9% of metastases were found near surgical sites and common metastasis locations included bone, lung, and lymph nodes.
  • Unique genetic mutations were observed in primary GBM and metastatic lesions, suggesting that understanding these changes could explain how GBMs spread beyond the CNS and aid future treatment strategies.
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  • The study aimed to evaluate the impact of the UK MHRA's March 2019 Risk Minimisation Measures (RMM) on the usage of fluoroquinolones using interrupted time series (ITS) methods.
  • It analyzed monthly and quarterly fluoroquinolone usage data from various healthcare settings between 2012 and 2022, employing segmented regression and ARIMA models to assess changes across different age groups.
  • Results showed significant reductions in fluoroquinolone usage after the RMM implementation across multiple databases, but some statistical issues such as heteroscedasticity and non-normality were observed in hospital-level data.
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Background: Pediatric recruitment into clinical trials is very challenging. A recruitment plan was designed to recruit healthy children (9-14 years) in a trial testing the 1-year effect of corn soluble fiber supplementation on bone mass. We evaluated the effectiveness and costs of the recruitment strategies used in this trial.

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Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using in vivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8 tissue-resident memory T (T) cell development. T cells depended on mitochondrial translation and respiration.

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  • The study explores how a sensory support intervention (SSI) program impacts quality of life in individuals with mild-to-moderate dementia who also have hearing and vision difficulties.
  • Researchers conducted a randomized controlled trial across seven clinics in five European countries, evaluating the effectiveness of an 18-week program compared to standard care.
  • The primary outcome measured was changes in health-related quality of life, using the Dementia Quality of Life Instrument (DEMQoL), with a total of 252 participants randomly assigned to either the SSI group or a control group receiving usual care.
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Study Design: Review article.

Objective: To provide a comprehensive review and update on the evaluation and management of Hangman's fractures.

Summary Of Background Data: Hangman's fractures are the second most common fracture of the C2 vertebrae, and the prevalence is increasing with our aging population.

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  • This study reviews how physical function (PROMIS PF scores) changes over time after lumbar fusion surgery, particularly focusing on the impact of functional comorbidities like heart failure or COPD on recovery.
  • Researchers analyzed data from 1,893 patients who underwent lumbar fusion from 2014 to 2022, comparing outcomes between those with and without comorbidities at regular intervals over two years.
  • Findings suggest that patients with functional comorbidities had different recovery trends, potentially highlighting the need for tailored rehabilitation strategies in post-surgical care.
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Background: Low physical activity among older adults is related to adverse health outcomes such as depression and loneliness, poor physical function and increased risk of falls. This study was designed to increase physical activity through a digital, group-based, physical activity and music intervention and to examine its effectiveness on social, mental and physical health outcomes.

Methods: Participants were 34 older adults (65 years +) recruited across four care homes in Scotland to a pilot study.

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Unlabelled: ZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumors in mice. Despite ZFTA-RELA's potent oncogenic potential, gene fusions are observed exclusively in childhood EPN, with tumors located distinctly in the supratentorial region of the central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZFTA-RELA.

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Myxopapillary ependymomas (MPEs) are rare tumors of the central nervous system, and outcomes are generally worse with recurrent disease. These tumors can rarely metastasize outside the neuraxis. We present a case of a 35-year-old female with a history of MPEs who developed extraneural metastases 11 years after her initial gross total resection.

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  • The study investigates the role of oxytocin in the interactions between children and dogs, analyzing how these interactions affect oxytocin release in both species.
  • Results show that children had increased oxytocin levels during interactions with their pet dogs compared to a control condition, with visual engagement playing a significant role in this response.
  • Additionally, children with a specific gene methylation pattern (OXTRm) exhibited different oxytocin responses, and while pet dogs displayed increased oxytocin, unfamiliar dogs showed a decrease, suggesting varied effects of companionship on social interactions.
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Oxytocin (OXT) is a peptide hormone and a neuropeptide that regulates various peripheral physiological processes and modulates behavioral responses in the central nervous system. While the humoral release occurs from the axons arriving at the median eminence, the neuropeptide is also released from oxytocinergic cell axons in various brain structures that contain its receptor, and from their dendrites in hypothalamic nuclei and potentially into the cerebrospinal fluid (CSF). Understanding oxytocin's complex functions requires the knowledge on patterns of oxytocinergic projections in relationship to its receptor (OXTR).

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  • FOXN1 is a transcription factor crucial for thymus development and T cell maturation, with variants potentially leading to T cell deficiencies at birth.
  • A study examined fraternal twins with a specific FOXN1 variant, highlighting their immune development and changes over time, including effects seen in their father with the same variant.
  • The FOXN1 variant shows different impacts on gene regulation, indicating that the type of mutation can influence its pathogenic effects, which may help in guiding treatment options and understanding infection or autoimmunity risks.
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The oxytocin system plays a role in social stress adaptation, and this role is likely to be particularly important in adolescence. One method of regulating the oxytocin system is through DNA methylation in the promoter of the oxytocin receptor gene (OXTRm), which reduces the gene's expression. This multi-method, longitudinal study, using a diverse community sample of 184 adolescents followed from age 13-28, examined the links between OXTRm and exposure to over-controlling parenting in adolescence and conflict with romantic partners and internalizing symptoms in adulthood.

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  • - Diamond-Blackfan anemia syndrome (DBAS) is a genetic disorder affecting bone marrow, often seen in infants, leading to low red blood cell counts and growth issues in about half of those affected.
  • - The condition results from a deficiency in one of 24 ribosomal protein genes, with mutations in RPS19 responsible for about 25% of cases.
  • - Researchers created induced pluripotent stem cell (iPSC) lines from two patients with different RPS19 mutations and also developed isogenic lines by correcting the mutations using a gene-editing technique called Cas9-mediated homology directed repair.
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DNA base damage is a major source of oncogenic mutations. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair.

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Postpartum hemorrhage, or excessive bleeding after birth, is a leading cause of maternal morbidity. A major cause of postpartum hemorrhage is uterine atony, tiring of the uterus which leads to ineffective contractions. Uterine contractions depend on oxytocin signaling in the myometrium, which in turn depends on expression of the oxytocin receptor (OXTR).

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3D cellular-specific epigenetic and transcriptomic reprogramming is critical to organogenesis and tumorigenesis. Here we dissect the distinct cell fitness in 2D (normoxia vs. chronic hypoxia) vs 3D (normoxia) culture conditions for a MYC-driven murine liver cancer model.

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Background: The innate immune system serves as the first line of host defense. Transforming growth factor-β-activated kinase 1 (TAK1) is a key regulator of innate immunity, cell survival, and cellular homeostasis. Because of its importance in immunity, several pathogens have evolved to carry TAK1 inhibitors.

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