Publications by authors named "Scott M Palisoul"

Article Synopsis
  • Deep learning applied to spatial transcriptomics (ST) helps understand how gene expression relates to tissue structure, allowing for large-scale studies that are more cost-effective compared to traditional methods.
  • Most research has focused on improving algorithms, but there’s a lack of understanding about how tissue preparation and imaging quality impact model training, which is crucial for clinical use.
  • A new enhanced tissue processing and imaging protocol was developed to improve model performance in predicting gene expression, showing promising results when compared to traditional methods using a study involving colorectal cancer patients.
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Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events.

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Nearly all cervical cancers are caused by persistent high-risk human papillomavirus (hrHPV) infection. There are 14 recognized hrHPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), and hrHPV genotypes 16 and 18 comprise approximately 66% of all cases worldwide. An additional 15% of cervical cancers are caused by hrHPV genotypes 31, 33, 45, 52, and 58.

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Article Synopsis
  • Spatial transcriptomics technologies are revolutionizing research by enabling the study of cellular and molecular dynamics within tissues, enhancing our understanding of development, disease, and tumor environments.
  • Photoaging, caused by sun exposure, affects skin health and is linked to skin cancer, and spatial transcriptomics can provide a reliable method for evaluating its impact and developing new treatments.
  • Despite challenges like high costs and patient variability in current technologies, using routine H&E-stained slides in combination with spatial transcriptomics can help analyze gene expression in skin specimens, potentially revealing valuable insights into photoaging and therapeutic efficacy.
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Graph-based deep learning has shown great promise in cancer histopathology image analysis by contextualizing complex morphology and structure across whole slide images to make high quality downstream outcome predictions (ex: prognostication). These methods rely on informative representations (i.e.

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Article Synopsis
  • Deep learning methods applied to spatial transcriptomics help uncover relationships between gene expression and tissue architecture, especially in diseases, but face challenges due to variability in tissue preparation and small study cohorts.
  • This research explores an improved tissue processing workflow using the Visium CytAssist assay to automate staining and optimize imaging, enabling better spatial transcriptomics profiling.
  • Results show that the enhanced workflow significantly improves the performance of deep learning models in predicting gene expression compared to traditional manual methods.
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Background: Spatial transcriptomics involves studying the spatial organization of gene expression within tissues, offering insights into the molecular diversity of tumors. While spatial gene expression is commonly amalgamated from 1-10 cells across 50-micron spots, recent methods have demonstrated the capability to disaggregate this information at subspot resolution by leveraging both expression and histological patterns. However, elucidating such information from histology alone presents a significant challenge but if solved can better permit spatial molecular analysis at cellular resolution for instances where Visium data is not available, reducing study costs.

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Over 150 000 Americans are diagnosed with colorectal cancer (CRC) every year, and annually over 50 000 individuals will die from CRC, necessitating improvements in screening, prognostication, disease management, and therapeutic options. Tumor metastasis is the primary factor related to the risk of recurrence and mortality. Yet, screening for nodal and distant metastasis is costly, and invasive and incomplete resection may hamper adequate assessment.

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Over 150,000 Americans are diagnosed with colorectal cancer (CRC) every year, and annually >50,000 individuals are estimated to die of CRC, necessitating improvements in screening, prognostication, disease management, and therapeutic options. CRC tumors are removed en bloc with surrounding vasculature and lymphatics. Examination of regional lymph nodes at the time of surgical resection is essential for prognostication.

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Spatially resolved characterization of the transcriptome and proteome promises to provide further clarity on cancer pathogenesis and etiology, which may inform future clinical practice through classifier development for clinical outcomes. However, batch effects may potentially obscure the ability of machine learning methods to derive complex associations within spatial omics data. Profiling thirty-five stage three colon cancer patients using the GeoMX Digital Spatial Profiler, we found that mixed-effects machine learning (MEML) methods† may provide utility for overcoming significant batch effects to communicate key and complex disease associations from spatial information.

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Significance: The study has confirmed the feasibility of using ultraviolet (UV) excitation to visualize and quantify desmoplasia in fresh tumor tissue of pancreatic adenocarcinoma (PDAC) in an orthotopic xenograft mouse model, which provides a useful imaging platform to evaluate acute therapeutic responses.

Aim: Stromal network of collagen prominent in PDAC tumors is examined by imaging fresh tissue samples stained with histological dyes. Fluorescence signals are color-transferred to mimic Masson's trichrome staining.

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