Publications by authors named "McKinley E"

Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data.

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Rapidly changing ocean conditions are resulting in changes in marine species and across entire ecosystems that, in turn, affect communities and individuals who rely on these resources for their livelihoods, culture, and sustenance. Marine social science, an emerging field that embraces diverse methods to understand human-ocean relationships, is increasingly called on to contribute to transdisciplinary ocean science that can inform the evidence-based policy and management needed to address these changes. Here, we review the state of marine social science as a growing field of study.

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Motivation: Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data.

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This work explored whether supplementing selective members of the interleukin-6 (IL6) cytokine family during in vitro bovine oocyte maturation affects maturation success, cumulus-oocyte complex (COC) gene expression, fertilization success, and embryo development potential. Human recombinant proteins for IL6, IL11, and leukemia inhibitory factor (LIF) were supplemented to COCs during the maturation period, then fertilization and embryo culture commenced without further cytokine supplementation. The first study determined that none of these cytokines influenced the rate that oocytes achieved arrest at meiosis II.

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Purpose/objective: Higher levels of resilience is associated with improved pain outcomes in chronic pain and other neurological populations, but the role of resilience in pain following spinal cord injury (SCI) remains unclear. This study examined resilience as a moderator in the relationship between perceived stress and both pain intensity and interference during acute rehabilitation for SCI.

Research Method/design: Individuals admitted to inpatient rehabilitation acutely following SCI ( = 57) completed measures of perceived stress, resilience, pain intensity, and interference.

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Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data from 31 human colorectal specimens enabled phylogeographic mapping of tumor evolution that revealed individualized progression trajectories and accompanying microenvironmental and clonal alterations. Phylogeographic mapping ordered genetic events, classified tumors by their evolutionary dynamics, and placed clonal regions along global pseudotemporal progression trajectories encompassing the chromosomal instability (CIN+) and hypermutated (HM) pathways.

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Article Synopsis
  • The current strategies for tackling issues at the ocean-climate intersection fail to fully consider the complex interactions between human, social, and ecological systems, hindering effective and equitable decision-making.
  • There is a call to adopt systems-informed decision-making that prioritizes interdisciplinary approaches and comprehensive impact assessments.
  • This shift aims to enhance collaboration among decision-makers and create fair solutions that recognize the diverse needs of all stakeholders involved in sustainable development.
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Motivation: Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data.

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Coastal saltmarshes provide globally important ecosystem services including 'blue carbon' sequestration, flood protection, pollutant remediation, habitat provision and cultural value. Large portions of marshes have been lost or fragmented as a result of land reclamation, embankment construction, and pollution. Sea level rise threatens marsh survival by blocking landward migration where coastlines have been developed.

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Background: Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination.

Purpose: To use MRI-measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer.

Study Type: Longitudinal; animal model.

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Thousands of oil and gas structures have been installed in the world's oceans over the past 70 years to meet the population's reliance on hydrocarbons. Over the last decade, there has been increased concern over how to handle decommissioning of this infrastructure when it reaches the end of its operational life. Complete or partial removal may or may not present the best option when considering potential impacts on the environment, society, technical feasibility, economy, and future asset liability.

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Background Elevated nonfasting triglycerides were associated with non-Alzheimer dementia in a recent study. However, this study neither evaluated the association of fasting triglycerides with incident cognitive impairment (ICI) nor adjusted for high-density lipoprotein cholesterol or hs-CRP (high-sensitivity C-reactive protein), known risk markers for ICI and dementia. Methods and Results We examined the association between fasting triglycerides and ICI among 16 170 participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study without cognitive impairment or a history of stroke at baseline in 2003 to 2007 and who had no stroke events during follow-up through September 2018.

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First introduced in the early 2000s, the concept of ocean literacy has evolved in recent years, not least since its inclusion as a mechanism for change within the United Nations Ocean Decade's goals. Building on early definitions of ocean literacy, there has been increasing recognition of a range of additional dimensions which contribute to an individual or collective sense of 'ocean literacy'. Drawing on existing research, and parallel and supporting concepts, e.

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Background: The clinicopathological significance of spatial tumor-infiltrating lymphocytes (TILs) subpopulations is not well studied due to lack of high-throughput scalable methodology for studies with large human sample sizes.

Objective: Establishing a cyclic fluorescent multiplex immunohistochemistry (mIHC/IF) method coupled with computer-assisted high-throughput quantitative analysis to evaluate associations of six TIL markers (CD3, CD8, CD20, CD56, FOXP3, and PD-L1) with clinicopathological factors of breast cancer.

Methods: Our 5-plex mIHC/IF staining was shown to be reliable and highly sensitive for labeling three biomarkers per tissue section.

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The importance of understanding the complexities of societal relationships with our global ocean, and how these influence sustainable management and effective, equitable governance, is crucial to addressing ocean challenges. Using established horizon scanning method, this paper explores current trends in marine social sciences through a survey of the global marine social science research and practitioner community (n = 106). We find that marine social sciences research is broad, covering themes relating to governance and decision-making, stakeholder participation and engagement, the socio-cultural dimensions of marine systems, ocean literacy, community-based and area-specific management, and the blue economy, and identify future research priorities highlighted by the community.

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In 2019, sands in nearby runoff streams from public beach showers were sampled on three islands in the State of Hawaii and tested for over 18 different petrochemical UV filters. Beach sands that are directly in the plume discharge of beach showers on three of the islands of Hawaii (Maui, Oahu, Hawai'i) were found to be contaminated with a wide array of petrochemical-based UV-filters that are found in sunscreens. Sands from beach showers across all three islands had a mean concentration of 5619 ng/g of oxybenzone with the highest concentration of 34,518 ng/g of oxybenzone at a beach shower in the Waikiki area of Honolulu.

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Unlabelled: Brain metastasis is a common characteristic of late-stage lung cancers. High doses of targeted radiotherapy can control tumor growth in the brain but can also result in radiotherapy-induced necrosis. Current methods are limited for distinguishing whether new parenchymal lesions following radiotherapy are recurrent tumors or radiotherapy-induced necrosis, but the clinical management of these two classes of lesions differs significantly.

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The biodiversity of marine and coastal habitats is experiencing unprecedented change. While there are well-known drivers of these changes, such as overexploitation, climate change and pollution, there are also relatively unknown emerging issues that are poorly understood or recognized that have potentially positive or negative impacts on marine and coastal ecosystems. In this inaugural Marine and Coastal Horizon Scan, we brought together 30 scientists, policymakers and practitioners with transdisciplinary expertise in marine and coastal systems to identify new issues that are likely to have a significant impact on the functioning and conservation of marine and coastal biodiversity over the next 5-10 years.

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Article Synopsis
  • The tumor microenvironment in colorectal tumors consists of diverse cell types, and understanding their interactions is crucial for grasping tumor complexity.
  • This study utilized single-cell RNA sequencing and other advanced imaging techniques to compare microenvironments in two mouse models of colorectal tumors — one sporadic and one driven by inflammation.
  • Results showed distinct differences between the tumor types, particularly in the abundance of cancer-associated fibroblasts and the presence of unique squamous cells, highlighting their roles in tumor progression, especially in inflammation-driven cancer models.
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Necrotic enteritis (NE), caused by Clostridium perfringens, is an intestinal disease with devastating economic losses to the poultry industry. NE is a complex disease and predisposing factors that compromise gut integrity are required to facilitate C. perfringens proliferation and toxin production.

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Study Objective: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for atherosclerotic cardiovascular disease (ASCVD) events in patients with diabetes and ASCVD. We assessed factors associated with initiating either medication among patients with diabetes and a prior myocardial infarction (MI).

Setting/participants: US adults ≥19 years old with private health insurance (MarketScan) or government health insurance (Medicare) who had diabetes and a prior MI and initiated a PCSK9i or an SGLT2i in 2017 or 2018.

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Increasingly, highly multiplexed tissue imaging methods are used to profile protein expression at the single-cell level. However, a critical limitation is the lack of robust cell segmentation tools for tissue sections. We present Multiplexed Image Resegmentation of Internal Aberrant Membranes (MIRIAM) that combines (a) a pipeline for cell segmentation and quantification that incorporates machine learning-based pixel classification to define cellular compartments, (b) a novel method for extending incomplete cell membranes, and (c) a deep learning-based cell shape descriptor.

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Motivation: Multiplexed imaging is a nascent single-cell assay with a complex data structure susceptible to technical variability that disrupts inference. These in situ methods are valuable in understanding cell-cell interactions, but few standardized processing steps or normalization techniques of multiplexed imaging data are available.

Results: We implement and compare data transformations and normalization algorithms in multiplexed imaging data.

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Article Synopsis
  • Colorectal cancers develop from polyps, and this study creates a detailed single-cell atlas of conventional adenomas and serrated polyps to understand their origins and characteristics.
  • The research reveals that adenomas stem from the growth of stem cells driven by WNT signaling, while serrated polyps emerge from differentiated cells undergoing gastric metaplasia, which leads to a damaged immune environment.
  • The findings highlight how changes in tumor cell differentiation affect immune responses and contribute to cancer progression, offering valuable insights for more targeted monitoring and prevention strategies for colorectal cancer.
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Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres.

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