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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Roy Otten; Chung Jung Mun; Daniel S. Shaw; Melvin N. Wilson; +1 Authors

    AbstractBackgrounds and aimsDespite the link between stress and addictive behavior in adulthood, little is known about how early life stress in families predicts the early emergence of substance use in adolescence. This study tested a developmental cascade model, proposing that early stressful life events and negative parent–child interaction covary, and both disrupt the refinement of inhibitory control, which evolves into problem behavior in middle/late childhood and subsequent substance use exploration in early adolescence.MethodsData came from the Early Steps Multisite study, a community sample of at‐risk families in the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon) and Charlottesville (Virginia) with children aged 2 years at the start of the study and 14 years at the last measurement (n = 364). Structural equation modeling was used to test the proposed model.ResultsEarly stressful life events and negative parent–child interaction assessed at ages 2–5 were negatively related to inhibitory control at ages 7 and 8. Low levels of inhibitory control were prognostic of childhood problem behavior at ages 9 and 10. Finally, late childhood problem behavior was associated with substance use at age 14. Parental drug use was directly related to substance use at age 14.ConclusionsEarly life stress may disrupt child inhibitory control, which can cascade into behavioral and peer problem behavior in childhood and, in turn, heighten the risk for early adolescent substance use.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    NARCIS
    Article . 2019
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    Article . 2019 . 2018
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    Radboud Repository
    Article . 2019
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    Article . 2018
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    Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2018
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      NARCIS
      Article . 2019
      Data sources: NARCIS
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2019 . 2018
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      Radboud Repository
      Article . 2019
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      Article . 2018
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      Article . 2018
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fabrice J. F. Laroche; Sheng Li; Ning Shen; Soo Kyung Hwang; +10 Authors

    Hyperactive sphingosine 1-phosphate (S1P) signaling is associated with a poor prognosis of triple-negative breast cancer (TNBC). Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses of human TNBC cells with zebrafish xenografts, we found that phosphorylation of S1P receptor 1 (S1P1) at threonine 236 (T236) is critical for TNBC dissemination. Compared to luminal breast cancer cells, TNBC cells exhibit a significant increase of phospho-S1P1 T236 but not the total S1P1 levels. Misexpression of phosphorylation-defective S1P1 T236A (alanine) decreases TNBC cell migration in vitro and disease invasion in zebrafish xenografts. Pharmacologic disruption of S1P1 T236 phosphorylation, using either a pan-AKT inhibitor (MK2206) or an S1P1 functional antagonist (FTY720, an FDA-approved drug for treating multiple sclerosis), suppresses TNBC cell migration in vitro and tumor invasion in vivo. Finally, we show that human TNBC cells with AKT activation and elevated phospho-S1P1 T236 are sensitive to FTY720-induced cytotoxic effects. These findings indicate that the AKT-enhanced phosphorylation of S1P1 T236 mediates much of the TNBC invasiveness, providing a potential biomarker to select TNBC patients for the clinical application of FTY720.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Cellsarrow_drop_down
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    Cells
    Other literature type . Article . 2023
    License: CC BY
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    Cells
    Article . 2023
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Cellsarrow_drop_down
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      Cells
      Other literature type . Article . 2023
      License: CC BY
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      Cells
      Article . 2023
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Spyros Papapetropoulos; Spyros Papapetropoulos; Angela Pontius; Elizabeth Finger; +16 Authors

    A comprehensive review of published literature was conducted to elucidate the genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, debilitating, and life-threatening neurodegenerative disorder for which disease-modifying therapies are not currently available. Details on potential efficacy endpoints for future interventional clinical trials in patients with ALSP and data related to the burden of the disease on patients and caregivers were also reviewed. The information in this position paper lays a foundation to establish an effective clinical rationale and address the clinical gaps for creation of a robust strategy to develop therapeutic agents for ALSP, as well as design future clinical trials, that have clinically meaningful and convergent endpoints.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Neurolo...arrow_drop_down
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    Frontiers in Neurology
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    Frontiers in Neurology
    Article . 2022
    Data sources: DOAJ-Articles
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    Frontiers in Neurology
    Article . 2022
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    Scholarship@Western
    Other literature type . 2022
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Frontiers in Neurolo...arrow_drop_down
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      Frontiers in Neurology
      Article
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      Frontiers in Neurology
      Article . 2022
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      Frontiers in Neurology
      Article . 2022
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      Scholarship@Western
      Other literature type . 2022
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    Authors: B. Ogan Mancarci; Lilah Toker; Shreejoy J. Tripathy; Brenna Li; +3 Authors

    Establishing the molecular diversity of cell types is crucial for the study of the nervous system. We compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single-cell RNA-sequencing (RNA-seq) studies. We used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. We further demonstrate that summarized expression of marker gene sets (MGSs) in bulk tissue data can be used to estimate the relative cell type abundance across samples. To facilitate use of this expanding resource, we provide a user-friendly web interface at www.neuroexpresso.org. Visual Abstract

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2017
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    bioRxiv
    Preprint . 2016
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    eNeuro
    Article . Preprint
    License: CC BY
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    eNeuro
    Article . 2017
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      Europe PubMed Central
      Article . 2017
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      bioRxiv
      Preprint . 2016
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      eNeuro
      Article . Preprint
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      eNeuro
      Article . 2017
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    Authors: Ryan M. Jones; Lulu Deng; Kogee Leung; Dallan McMahon; +2 Authors

    Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening recently entered clinical testing for targeted drug delivery to the brain. Sources of variability exist in the current procedures, motivating the development of real-time monitoring and control techniques to improve treatment safety and efficacy. Here we used three-dimensional (3D) transcranial microbubble imaging to calibrate FUS exposure levels for volumetric BBB opening. Methods: Using a sparse hemispherical transmit/receive ultrasound phased array, pulsed ultrasound was focused transcranially into the thalamus of rabbits during microbubble infusion and multi-channel 3D beamforming was performed online with receiver signals captured at the subharmonic frequency. Pressures were increased pulse-by-pulse until subharmonic activity was detected on acoustic imaging (psub), and tissue volumes surrounding the calibration point were exposed at 50-100%psub via rapid electronic beam steering. Results: Spatially-coherent subharmonic microbubble activity was successfully reconstructed transcranially in vivo during calibration sonications. Multi-point exposures induced volumetric regions of elevated BBB permeability assessed via contrast-enhanced magnetic resonance imaging (MRI). At exposure levels ≥75%psub, MRI and histological examination occasionally revealed tissue damage, whereas sonications at 50%psub were performed safely. Substantial intra-grid variability of FUS-induced bioeffects was observed via MRI, prompting future development of multi-point calibration schemes for improved treatment consistency. Receiver array sparsity and sensor configuration had substantial impacts on subharmonic detection sensitivity, and are factors that should be considered when designing next-generation clinical FUS brain therapy systems. Conclusion: Our findings suggest that 3D subharmonic imaging can be used to calibrate exposure levels for safe FUS-induced volumetric BBB opening, and should be explored further as a method for cavitation-mediated treatment guidance.

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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Europe PubMed Central
    Article . 2018
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    Theranostics
    Article . 2018
    Data sources: Crossref
    https://pubmed.ncbi.nlm.nih.go...
    Other literature type . 2018
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      Europe PubMed Central
      Article . 2018
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      Europe PubMed Central
      Article . 2018
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      Theranostics
      Article . 2018
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      Other literature type . 2018
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    Authors: Selena Ahmed; Shauna Downs; Jessica Fanzo;

    The food system is responsible for some of society's most pressing sustainability challenges. Dietary guidelines are one policy tool to help address the multiple sustainability challenges associated with food systems through dietary recommendations that better support environmental and human well-being. This article develops and applies a sustainability framework scoring tool comprised of four key dimensions (environmental, economic, human health, and sociocultural and political) and 32 sub-dimensions of sustainable food systems for the analysis and modification of national dietary guidelines. Two coders pilot tested the framework to quantify the occurrence of sustainability dimensions and sub-dimensions in national and regional dietary guidelines of 12 randomly selected high-income and upper-middle income countries including Albania, Australia, Brazil, the Grenadines, Grenada, Qatar, Netherlands, Nordic Countries, St. Vincent, Sweden, Thailand, the United Kingdom, and the United States. Sustainability Dimension Scores (SDS) were calculated as a percentage of the occurrence of the eight sub-dimensions comprising each sustainability dimension and Total Sustainability Scores (TSS) were calculated as a percentage of the occurrence of the 32 sub-dimensions in each guideline. Inter-rater reliability of TSS and SDS indicated high validity of applying the sustainability framework for dietary guidelines. SDS varied between the four sustainability dimensions with human health being the most represented in the dietary guidelines examined, as hypothesized (average SDS score of 83%; range from 50 to 100%). Significant differences (p < 0.0001) were found in mean SDS between the four sustainability dimensions. Overall, results indicate that the ecological (average SDS score of 31%; range from 0 to 100%) economic (average SDS score of 29%; range from 0 to 100%), and socio-cultural and political (average SDS score of 44%; range of 0–100%) dimensions of sustainability are underrepresented in the examined national dietary guidelines with significant differences in SDS between guidelines (p < 0.0001). TSS varied by country between 12 and 74% with a mean score of 36% (± 20%). Brazil had the highest TSS (74%) followed by Australia (69%). The sustainability framework presented here can be applied by policy makers, researchers, and practitioners to identify gaps and opportunities to modify national dietary guidelines and associated programs for transforming food systems through diets that support planetary health.

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    Frontiers in Sustainable Food Systems
    Article . 2019
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    Frontiers in Sustainable Food Systems
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    DOAJ-Articles
    Article . 2019
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      Frontiers in Sustainable Food Systems
      Article . 2019
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      Frontiers in Sustainable Food Systems
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    Authors: Lawson, Christine; Schlaepfer, David D.;

    Cell migration requires the coordination of adhesion site assembly and turnover. Canonical models for nascent adhesion formation postulate that integrin binding to extracellular matrix (ECM) proteins results in the rapid recruitment of cytoskeletal proteins such as talin and paxillin to integrin cytoplasmic domains. It is thought that integrin-talin clusters recruit and activate tyrosine kinases such as focal adhesion kinase (FAK). However, the molecular connections of this linkage remain unresolved. Our recent findings support an alternative model whereby FAK recruits talin to new sites of β1 integrin-mediated adhesion in mouse embryonic fibroblasts and human ovarian carcinoma cells. This is dependent on a direct binding interaction between FAK and talin and occurs independently of direct talin binding to β1 integrin. Herein, we discuss differences between nascent and mature adhesions, interactions between FAK, talin and paxillin, possible mechanisms of FAK activation and how this FAK-talin complex may function to promote cell motility through increased adhesion turnover.

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    Europe PubMed Central
    Article . 2012
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      Europe PubMed Central
      Article . 2012
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    Authors: Eskildsen, S.F.; Coupe, P.; Fonov, V.; Manjon, J.V.; +8 Authors

    Brain extraction is an important step in the analysis of brain images. The variability in brain morphology and the difference in intensity characteristics due to imaging sequences make the development of a general purpose brain extraction algorithm challenging. To address this issue, we propose a new robust method (BEaST) dedicated to produce consistent and accurate brain extraction. This method is based on nonlocal segmentation embedded in a multi-resolution framework. A library of 80 priors is semi-automatically constructed from the NIH-sponsored MRI study of normal brain development, the International Consortium for Brain Mapping, and the Alzheimer's Disease Neuroimaging Initiative databases. In testing, a mean Dice similarity coefficient of 0.9834 ± 0.0053 was obtained when performing leave-one-out cross validation selecting only 20 priors from the library. Validation using the online Segmentation Validation Engine resulted in a top ranking position with a mean Dice coefficient of 0.9781 ± 0.0047. Robustness of BEaST is demonstrated on all baseline ADNI data, resulting in a very low failure rate. The segmentation accuracy of the method is better than two widely used publicly available methods and recent state-of-the-art hybrid approaches. BEaST provides results comparable to a recent label fusion approach, while being 40 times faster and requiring a much smaller library of priors. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30AG010129, K01 AG030514, and the Dana Foundation.

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    Article . 2011
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    Article . 2012
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    Authors: Simpson, I.J.A.; Cardoso, M.J.; Modat, M.; Cash, D.M.; +4 Authors

    This paper introduces a novel method for inferring spatially varying regularisa- tion in non-linear registration. This is achieved through full Bayesian inference on a probabilistic registration model, where the prior on the transformation parameters is parameterised as a weighted mixture of spatially localised com- ponents. Such an approach has the advantage of allowing the registration to be more flexibly driven by the data than a traditional globally defined regularisation penalty, such as bending energy. The proposed method adaptively determines the influence of the prior in a local region. The strength of the prior may be reduced in areas where the data better support deformations, or can enforce a stronger constraint in less informative areas. Consequently, the use of such a spatially adaptive prior may reduce unwanted impacts of regularisation on the inferred transformation. This is especially important for applications where the deformation field itself is of interest, such as tensor based morphometry. The proposed approach is demonstrated using synthetic images, and with application to tensor based morphometry analysis of subjects with Alzheimer’s disease and healthy controls. The results indicate that using the proposed spatially adap- tive prior leads to sparser deformations, which provide better localisation of regional volume change. Additionally, the proposed regularisation model leads to more data driven and localised maps of registration uncertainty. This paper also demonstrates for the first time the use of Bayesian model comparison for selecting different types of regularisation.

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    Medical Image Analysis
    Article . 2015
    License: CC BY
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      Medical Image Analysis
      Article . 2015
      License: CC BY
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    Authors: Pereira, Telma; Ferreira, Francisco; Cardoso, Sandra; Silva, Dina; +3 Authors

    Stability and classification performance of classification models learnt with an incremental number of (ranked) features and using NB, DT, LR, SVM Poly and SVM RBF, per time windows, using ADNI and CCC data. RPT thresholds with β set as 0.1, 1 and 10 are illustrated. (DOCX 2920 kb)

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10,906 Research products
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Roy Otten; Chung Jung Mun; Daniel S. Shaw; Melvin N. Wilson; +1 Authors

    AbstractBackgrounds and aimsDespite the link between stress and addictive behavior in adulthood, little is known about how early life stress in families predicts the early emergence of substance use in adolescence. This study tested a developmental cascade model, proposing that early stressful life events and negative parent–child interaction covary, and both disrupt the refinement of inhibitory control, which evolves into problem behavior in middle/late childhood and subsequent substance use exploration in early adolescence.MethodsData came from the Early Steps Multisite study, a community sample of at‐risk families in the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon) and Charlottesville (Virginia) with children aged 2 years at the start of the study and 14 years at the last measurement (n = 364). Structural equation modeling was used to test the proposed model.ResultsEarly stressful life events and negative parent–child interaction assessed at ages 2–5 were negatively related to inhibitory control at ages 7 and 8. Low levels of inhibitory control were prognostic of childhood problem behavior at ages 9 and 10. Finally, late childhood problem behavior was associated with substance use at age 14. Parental drug use was directly related to substance use at age 14.ConclusionsEarly life stress may disrupt child inhibitory control, which can cascade into behavioral and peer problem behavior in childhood and, in turn, heighten the risk for early adolescent substance use.

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    Europe PubMed Central
    Article . 2018
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    Radboud Repository
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    Authors: Fabrice J. F. Laroche; Sheng Li; Ning Shen; Soo Kyung Hwang; +10 Authors

    Hyperactive sphingosine 1-phosphate (S1P) signaling is associated with a poor prognosis of triple-negative breast cancer (TNBC). Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses of human TNBC cells with zebrafish xenografts, we found that phosphorylation of S1P receptor 1 (S1P1) at threonine 236 (T236) is critical for TNBC dissemination. Compared to luminal breast cancer cells, TNBC cells exhibit a significant increase of phospho-S1P1 T236 but not the total S1P1 levels. Misexpression of phosphorylation-defective S1P1 T236A (alanine) decreases TNBC cell migration in vitro and disease invasion in zebrafish xenografts. Pharmacologic disruption of S1P1 T236 phosphorylation, using either a pan-AKT inhibitor (MK2206) or an S1P1 functional antagonist (FTY720, an FDA-approved drug for treating multiple sclerosis), suppresses TNBC cell migration in vitro and tumor invasion in vivo. Finally, we show that human TNBC cells with AKT activation and elevated phospho-S1P1 T236 are sensitive to FTY720-induced cytotoxic effects. These findings indicate that the AKT-enhanced phosphorylation of S1P1 T236 mediates much of the TNBC invasiveness, providing a potential biomarker to select TNBC patients for the clinical application of FTY720.

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    Cells
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    Cells
    Article . 2023