Publications by authors named "Leary J"

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

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Introduction: Despite continued improvement in post-sepsis survival, long term morbidity and mortality remain high. Chronic critical illness (CCI), defined as persistent inflammation and organ injury requiring prolonged intensive care, is a harbinger of poor long-term outcomes in sepsis survivors. Current dogma states that sepsis survivors are immunosuppressed, particularly in CCI.

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Elevation of depressed skull fractures in pediatric patients is indicated when the depression extends below the level of the inner table. Although open surgical reduction is an option for treatment, closed vacuum-assisted elevation has been found to have a high success rate and low complication rates when employed in children less than 6 months of age without disruption of the cortex. In this article, we describe two recent cases from our institution and summarize the reported cases in the literature including information about fracture specifics, device used, technical approach, and success rate of the procedure.

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Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI.

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A captive sand tiger shark () presented with progressive, hard, raised, miliary skin lesions localized to the lateral trunk and peduncle. Histopathologic evaluation of biopsy samples revealed dysplastic proliferation of odontogenic epithelium with the production of collagenous material. Inclusion bodies and viral particles were not observed with light or transmission electron microscopy, respectively.

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Article Synopsis
  • - The study investigated the relationship between Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status in patients with urothelial carcinoma (UC) receiving immune checkpoint inhibitors (ICI), focusing on overall survival (OS).
  • - Results showed that patients with a higher TMB (≥10 mut/Mb) generally experienced longer median OS compared to those with lower TMB, although these differences weren't always statistically significant.
  • - Notably, patients treated with maintenance avelumab had a significantly better OS when TMB was high (61 months vs. 17 months for low TMB), indicating potential benefits of ICI based on TMB and MSI status, warranting further investigation.
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Numerous aspects of cellular signaling are regulated by the kinome-the network of over 500 protein kinases that guides and modulates information transfer throughout the cell. The key role played by both individual kinases and assemblies of kinases organized into functional subnetworks leads to kinome dysregulation driving many diseases, particularly cancer. In the case of pancreatic ductal adenocarcinoma (PDAC), a variety of kinases and associated signaling pathways have been identified for their key role in the establishment of disease as well as its progression.

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Purpose: Rising rates of early-onset colon cancer (EOCC) present challenges in deciding how to optimally treat patients. Although standard of care for stage II CC is surgical resection, adding chemotherapy for high-risk disease, evidence suggests treatment selection may differ by age. We investigated whether adjuvant chemotherapy (AC) administration rates differ between patients with early- and later-onset stage II CC.

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Proliferative gill disease (PGD), caused by the myxozoan , has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, , was described in channel () × blue () hybrid catfish. Targeted metagenomic sequencing and hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive infections and PGD cases.

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Article Synopsis
  • Researchers have identified distinct subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma using single-cell RNA sequencing, but their clinical importance was uncertain.
  • They developed a classifier named DeCAF to classify CAF subtypes based on RNA sequencing data, which has been validated in various cancer types and shown to have unique histological features and prognostic value.
  • DeCAF provides a reliable method to understand CAF roles in cancer, assisting in the development of targeted therapies by distinguishing between permissive and restraining CAF subtypes.
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Single-cell RNA sequencing (scRNA-seq) experiments have become instrumental in developmental and differentiation studies, enabling the profiling of cells at a single or multiple time-points to uncover subtle variations in expression profiles reflecting underlying biological processes. Benchmarking studies have compared many of the computational methods used to reconstruct cellular dynamics; however, researchers still encounter challenges in their analysis due to uncertainty with respect to selecting the most appropriate methods and parameters. Even among universal data processing steps used by trajectory inference methods such as feature selection and dimension reduction, trajectory methods' performances are highly dataset-specific.

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Article Synopsis
  • Sepsis leads to specific immune system changes, particularly the increase of myeloid-derived suppressor cells (MDSCs), which help control inflammation but can linger in those with ongoing critical illness.
  • The study employs advanced techniques like Cellular Indexing of Transcriptomes and Epitopes by Sequencing to analyze MDSC types based on gene expression and biological functions.
  • Findings reveal a new lineage and differentiation pathway for MDSCs following sepsis, emphasizing their variable responses related to patient outcomes and demonstrating their ability to change, contradicting the previous belief of a fixed lineage.
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Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. As classical and nonclassical monocytes are key leukocytes in both the innate and adaptive immune systems, we sought to delineate the transcriptomic response of these cell types.

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Article Synopsis
  • - The study examines genomic alterations (GA) in patients with urothelial bladder cancer (UBC), focusing on those with ERBB2 mutations and amplifications, and comparing them to patients with wild-type ERBB2.
  • - Findings show that 6.3% of UBC cases have short variant GAs in the ERBB2 extracellular domain, 2.7% in the kinase domain, and 9.1% show ERBB2 amplification, while 81.9% are ERBB2 wild-type.
  • - The analysis indicates that ERBB2-altered cases exhibit higher tumor mutational burden and specific genetic changes compared to wild-type ERBB2 cases, with notable associations found between various genetic markers
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Article Synopsis
  • The study aimed to assess how a new social risk screening and referral system affected a community hospital's pediatric unit after its implementation in April 2022.
  • Data was collected from patients aged 0 to 17 during a year before and after the program's launch, analyzing changes in identifying social risks and consulting with social work.
  • Results showed a significant increase in the identification of social risks, more frequent and quicker social work consultations, and improved communication about these risks in discharge summaries after the implementation.
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Shallow lakes are typically dominated by macrophytes, which have important functional roles regulating trophic conditions and creating biological habitat. Macrophytes have been shown to strongly influence water chemistry and shape microbial communities in shallow lakes. In Florida, many large, shallow lakes are dominated by alien invasive, submersed macrophytes, such as hydrilla (Hydrilla verticillata [L.

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Single-cell RNA sequencing (scRNA-seq) experiments have become instrumental in developmental and differentiation studies, enabling the profiling of cells at a single or multiple time-points to uncover subtle variations in expression profiles reflecting underlying biological processes. Benchmarking studies have compared many of the computational methods used to reconstruct cellular dynamics, however researchers still encounter challenges in their analysis due to uncertainties in selecting the most appropriate methods and parameters. Even among universal data processing steps used by trajectory inference methods such as feature selection and dimension reduction, trajectory methods' performances are highly dataset-specific.

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The rapid proliferation of trajectory inference methods for single-cell RNA-seq data has allowed researchers to investigate complex biological processes by examining underlying gene expression dynamics. After estimating a latent cell ordering, statistical models are used to determine which genes exhibit changes in expression that are significantly associated with progression through the biological trajectory. While a few techniques for performing trajectory differential expression exist, most rely on the flexibility of generalized additive models in order to account for the inherent nonlinearity of changes in gene expression.

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Treatment of large dysplastic middle cerebral artery (MCA) aneurysms can be challenging.1 2 Catheterization of M2 branches at hyperacute angles often requires an 'around the world' approach/microcatheter reduction, which can be accomplished with rapid pull,3 balloon anchor,4 and stent anchor5 techniques. In this video video 1, Atlas stents (Stryker) are used for double microcatheter reduction along with Y stent assisted coil embolization (Video 1).

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Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration.

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Objectives: In response to evidence linking social risk factors and adverse health outcomes, new incentives have emerged for hospitals to screen for adverse social determinants of health (SDOH). However, little information is available about the current state of social risk-related care practices among children's hospitals. To address outstanding knowledge gaps, we sought to describe social risk-related care practices among a national sample of children's hospitals.

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Motivation: Single-cell RNA-sequencing (scRNA-seq) has enabled the molecular profiling of thousands to millions of cells simultaneously in biologically heterogenous samples. Currently, the common practice in scRNA-seq is to determine cell type labels through unsupervised clustering and the examination of cluster-specific genes. However, even small differences in analysis and parameter choosing can greatly alter clustering results and thus impose great influence on which cell types are identified.

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