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  1. Article ; Online: Defining a universal measurement unit and scale for gross motor development

    Bryant A. Seamon / Cynthia L. Sears / Emily Anderson / Craig A. Velozo

    Frontiers in Rehabilitation Sciences, Vol

    2024  Volume 5

    Abstract: IntroductionThe ability of children to accomplish progressively more difficult gross motor tasks follows a predictable sequence that has been well documented as part of development. Current existing instruments were developed independently using ... ...

    Abstract IntroductionThe ability of children to accomplish progressively more difficult gross motor tasks follows a predictable sequence that has been well documented as part of development. Current existing instruments were developed independently using classical test theory methods which led to the lack of a universal measurement scale and unit. The purpose of this study was to test a specification equation, anchored to commonly accepted and reproducible tasks in gross motor development, to generate a universal measurement scale and unit of measurement, called the Gross Motor (GM) unit.MethodsWe rated component measures for each of the gross motor development tasks on the Gross Motor Function Measure-66 (GMFM). The GMFM is a gross motor development measure created with Rasch measurement theory to quantify observed difficulty levels measured on an interval scale. Component measures for body position, movement, and support were based on hypothesized contributions to gross motor development based on theory. Forward stepwise linear regression was used to test a specification equation. The specification equation was anchored to reference points to fix a unit size.ResultsOur specification equation explained 87% of the variance in observed gross motor task difficulty. Predicted difficulty for gross motor tasks was strongly associated with observed task difficulty (r = 0.94, p < 0.0001). Our specification equation was anchored to 1) lying supine (0 GM units) and 2) walking unsupported (100 GM units) setting the size of the GM unit to 1/100 of the distance between lying supine and unsupported walking.DiscussionOur specification equation allows for experimental testing of gross motor development theories. This approach provides a framework for refining our understanding and measurement of gross motor development and creates a universal scale and unit. We expect that this will facilitate placing many, if not all, current gross motor development instruments on the same measurement scale.
    Keywords measures ; pediatrics ; growth ; child development ; motor skills ; Other systems of medicine ; RZ201-999 ; Medical technology ; R855-855.5
    Subject code 796
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The who, where and how of fusobacteria and colon cancer

    Cynthia L Sears

    eLife, Vol

    2018  Volume 7

    Abstract: The association between the bacterium Fusobacterium nucleatum and human colon cancer is more complicated than it first appeared. ...

    Abstract The association between the bacterium Fusobacterium nucleatum and human colon cancer is more complicated than it first appeared.
    Keywords Reproducibility Project: Cancer Biology ; replication ; metascience ; reproducibility ; Fusobacterium nucleatum ; colorectal carcinoma ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Impact of the gut microbiome on the genome and epigenome of colon epithelial cells

    Jawara Allen / Cynthia L. Sears

    Genome Medicine, Vol 11, Iss 1, Pp 1-

    contributions to colorectal cancer development

    2019  Volume 18

    Abstract: Abstract In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool ...

    Abstract Abstract In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Subject code 306
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Next-generation sequencing

    Caroline R. Wensel / Jennifer L. Pluznick / Steven L. Salzberg / Cynthia L. Sears

    The Journal of Clinical Investigation, Vol 132, Iss

    insights to advance clinical investigations of the microbiome

    2022  Volume 7

    Abstract: Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene ... ...

    Abstract Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years.
    Keywords Medicine ; R
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Impact of the microbiome on checkpoint inhibitor treatment in patients with non-small cell lung cancer and melanoma

    Fyza Y. Shaikh / Joell J. Gills / Cynthia L. Sears

    EBioMedicine, Vol 48, Iss , Pp 642-

    2019  Volume 647

    Abstract: The microbiome is increasingly recognized for its role in multiple aspects of cancer development and treatment, specifically in response to checkpoint inhibitors. While checkpoint inhibitors have revolutionized cancer treatment by producing durable anti- ... ...

    Abstract The microbiome is increasingly recognized for its role in multiple aspects of cancer development and treatment, specifically in response to checkpoint inhibitors. While checkpoint inhibitors have revolutionized cancer treatment by producing durable anti-tumor responses, only a minority of patients respond to the available immunotherapy drugs and accurate, sensitive and specific microbiome predictors of response to treatment remain elusive. Additionally, the specific mechanisms linking the microbiome and host immunological responses remain unclear. In this review, we examine the evidence for the gut microbiome's association with anti-tumor responses to checkpoint inhibitors in the treatment of melanoma, non-small cell lung cancer, and renal cell carcinoma. Furthermore, we discuss the current evidence available from murine models seeking to explain the immunological mechanisms that may drive this process. While this work is promising in defining the impact of gut microbiota in cancer treatment, many unanswered questions indicate the need for additional human and experimental studies. Keywords: Microbiome, Immunotherapy, Checkpoint inhibitors, NSCLC, Melanoma
    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

    Annemarie Boleij / Payam Fathi / William Dalton / Ben Park / Xinqun Wu / David Huso / Jawara Allen / Sepideh Besharati / Robert A. Anders / Franck Housseau / Amanda E. Mackenzie / Laura Jenkins / Graeme. Milligan / Shaoguang Wu / Cynthia L. Sears

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Boleij et al. show that G protein-coupled receptor 35 (GPR35) regulates the responses to enterotoxigenic Bacteroides fragilis (ETBF) in colonic epithelial cells. They find that GPR35-deficiency nearly protected mice from ETBF-induced death, suggesting ... ...

    Abstract Boleij et al. show that G protein-coupled receptor 35 (GPR35) regulates the responses to enterotoxigenic Bacteroides fragilis (ETBF) in colonic epithelial cells. They find that GPR35-deficiency nearly protected mice from ETBF-induced death, suggesting the importance of GPR35 in sensing ETBF in the colon.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Clinically adaptable polymer enables simultaneous spatial analysis of colonic tissues and biofilms

    Mary C. Macedonia / Julia L. Drewes / Nicholas O. Markham / Alan J. Simmons / Joseph T. Roland / Paige N. Vega / Cherie’ R. Scurrah / Robert J. Coffey / Martha J. Shrubsole / Cynthia L. Sears / Ken S. Lau

    npj Biofilms and Microbiomes, Vol 6, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: Abstract Microbial influences on host cells depend upon the identities of the microbes, their spatial localization, and the responses they invoke on specific host cell populations. Multimodal analyses of both microbes and host cells in a spatially ... ...

    Abstract Abstract Microbial influences on host cells depend upon the identities of the microbes, their spatial localization, and the responses they invoke on specific host cell populations. Multimodal analyses of both microbes and host cells in a spatially resolved fashion would enable studies into these complex interactions in native tissue environments, potentially in clinical specimens. While techniques to preserve each of the microbial and host cell compartments have been used to examine tissues and microbes separately, we endeavored to develop approaches to simultaneously analyze both compartments. Herein, we established an original method for mucus preservation using Poloxamer 407 (also known as Pluronic F-127), a thermoreversible polymer with mucus-adhesive characteristics. We demonstrate that this approach can preserve spatially-defined compartments of the mucus bi-layer in the colon and the bacterial communities within, compared with their marked absence when tissues were processed with traditional formalin-fixed paraffin-embedded (FFPE) pipelines. Additionally, antigens for antibody staining of host cells were preserved and signal intensity for 16S rRNA fluorescence in situ hybridization (FISH) was enhanced in poloxamer-fixed samples. This in turn enabled us to integrate multimodal analysis using a modified multiplex immunofluorescence (MxIF) protocol. Importantly, we have formulated Poloxamer 407 to polymerize and cross-link at room temperature for use in clinical workflows. These results suggest that the fixative formulation of Poloxamer 407 can be integrated into biospecimen collection pipelines for simultaneous analysis of microbes and host cells.
    Keywords Microbial ecology ; QR100-130
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation

    Kai Fu / Xin Sun / Eric M Wier / Andrea Hodgson / Yue Liu / Cynthia L Sears / Fengyi Wan

    eLife, Vol

    2016  Volume 5

    Abstract: Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade ... ...

    Abstract Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade linking DNA damage and NF-κB activation is poorly understood. Here we report that Src-associated-substrate-during-mitosis-of-68kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-κB regulator in genotoxic stress-initiated signaling pathway. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells are hypersensitive to genotoxicity caused by DNA damaging agents. Upregulated Sam68 coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription in human and mouse colon cancer. Knockdown of Sam68 sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and genetic deletion of Sam68 dampens colon tumor burden in mice. Together our data reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is crucial for colon tumorigenesis.
    Keywords NF-kB ; colon cancer ; signal transduction ; DNA damage responses ; Sam68 ; KHDRBS1 ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2016-07-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Author Correction

    Julia L. Drewes / James R. White / Christine M. Dejea / Payam Fathi / Thevambiga Iyadorai / Jamuna Vadivelu / April C. Roslani / Elizabeth C. Wick / Emmanuel F. Mongodin / Mun Fai Loke / Kumar Thulasi / Han Ming Gan / Khean Lee Goh / Hoong Yin Chong / Sandip Kumar / Jane W. Wanyiri / Cynthia L. Sears

    npj Biofilms and Microbiomes, Vol 5, Iss 1, Pp 1-

    High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

    2019  Volume 1

    Abstract: In this Article, in the section entitled ‘Quantitative real-time PCR’ within the Supplementary Methods, the probe for the Bacteroides fragilis 16S real-time PCR reaction was listed incorrectly as 5ʹHEX-AGGGACTGGAAGGCTTTACTGCTTC-3ʹBHQ1. The correct probe ... ...

    Abstract In this Article, in the section entitled ‘Quantitative real-time PCR’ within the Supplementary Methods, the probe for the Bacteroides fragilis 16S real-time PCR reaction was listed incorrectly as 5ʹHEX-AGGGACTGGAAGGCTTTACTGCTTC-3ʹBHQ1. The correct probe for Bacteroides fragilis 16S should be listed as 5ʹHEX-ACACGTATCCAACCTGCCCTTTACTCG-3ʹBHQ1. The mistake was a result of a copy and paste error with a different primer set targeting a B. fragilis toxin gene. All qPCR reactions were performed using the correct probe, and therefore no data were affected.
    Keywords Microbial ecology ; QR100-130
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

    Julia L. Drewes / James R. White / Christine M. Dejea / Payam Fathi / Thevambiga Iyadorai / Jamuna Vadivelu / April C. Roslani / Elizabeth C. Wick / Emmanuel F. Mongodin / Mun Fai Loke / Kumar Thulasi / Han Ming Gan / Khean Lee Goh / Hoong Yin Chong / Sandip Kumar / Jane W. Wanyiri / Cynthia L. Sears

    npj Biofilms and Microbiomes, Vol 3, Iss 1, Pp 1-

    2017  Volume 12

    Abstract: Bowel cancer: Spotlight of suspicion on bacteria Many studies have found a link between gut microbes and bowel cancer, the third most common cancer worldwide. The details of the association, however, have remained elusive. Researchers in the USA and ... ...

    Abstract Bowel cancer: Spotlight of suspicion on bacteria Many studies have found a link between gut microbes and bowel cancer, the third most common cancer worldwide. The details of the association, however, have remained elusive. Researchers in the USA and Malaysia, led by Dr. Cynthia Sears at John Hopkins School of Medicine in Maryland, examined mucosal biofilm status by fluorescence microscopy and performed a meta-analysis of bacterial genetic associations in stool and colon tissues to clarify the connection. They found that bowel cancers were enriched in invasive bacterial biofilms as well as several specific gut and oral species, including one - Fusobacterium nucleatum - known to promote tumorigenesis in mouse models. Analyzing gut microbial populations might help assess bowel cancer risk. Further research is needed, however, to determine if these bacteria directly contribute to disease causality.
    Keywords Microbial ecology ; QR100-130
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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