481 research outputs found

    Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

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    Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

    The Helping Networks of Transgender Women Living with HIV

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    Transgender women living with HIV face significant barriers to healthcare that may be best addressed through community-centered interventions holistically focused on their HIV-related, gender-related, and other important needs. Community health ambassador (CHA) interventions (education and training programs designed to engage communities and community leaders in health promotion) may be an effective option, though information about the natural helping networks of this vulnerable population is too limited to inform the implementation of this approach. This study uses social network analysis to describe the natural helping networks of transgender women living with HIV, their help-seeking patterns for HIV-related, gender-related, and ancillary resources, and the characteristics of potential network ambassadors. From February to August 2019, transgender women living with HIV in the US (N = 231) participated a 30-min online survey asking them to describe their natural helping networks (N = 1054). On average, participants were embedded within natural helping networks consisting of 4-5 people. They were more likely to seek help from informal network members vs. formal service providers (p < .01), and from chosen family and partners/spouses (p < .05) above other social connections. Older network members (p < .01), other transgender women (p < .05), and those with whom they regularly engaged face-to-face (p < .01) (vs. social technology) were identified as potential network ambassadors for HIV-, gender-related, and other important issues. These findings suggest an opportunity to develop CHA interventions that leverage existing help networks and potential network ambassadors to promote equitable access to HIV, gender-affirming, and other crucial resources among this medically underserved group

    Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

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    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

    The disruption of proteostasis in neurodegenerative diseases

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    Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

    A separated vortex ring underlies the flight of the dandelion

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    Wind-dispersed plants have evolved ingenious ways to lift their seeds1,2. The common dandelion uses a bundle of drag-enhancing bristles (the pappus) that helps to keep their seeds aloft. This passive flight mechanism is highly effective, enabling seed dispersal over formidable distances3,4; however, the physics underpinning pappus-mediated flight remains unresolved. Here we visualized the flow around dandelion seeds, uncovering an extraordinary type of vortex. This vortex is a ring of recirculating fluid, which is detached owing to the flow passing through the pappus. We hypothesized that the circular disk-like geometry and the porosity of the pappus are the key design features that enable the formation of the separated vortex ring. The porosity gradient was surveyed using microfabricated disks, and a disk with a similar porosity was found to be able to recapitulate the flow behaviour of the pappus. The porosity of the dandelion pappus appears to be tuned precisely to stabilize the vortex, while maximizing aerodynamic loading and minimizing material requirements. The discovery of the separated vortex ring provides evidence of the existence of a new class of fluid behaviour around fluid-immersed bodies that may underlie locomotion, weight reduction and particle retention in biological and manmade structures

    Ocean Surface Winds Drive Dynamics of Transoceanic Aerial Movements

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    Global wind patterns influence dispersal and migration processes of aerial organisms, propagules and particles, which ultimately could determine the dynamics of colonizations, invasions or spread of pathogens. However, studying how wind-mediated movements actually happen has been hampered so far by the lack of high resolution global wind data as well as the impossibility to track aerial movements. Using concurrent data on winds and actual pathways of a tracked seabird, here we show that oceanic winds define spatiotemporal pathways and barriers for large-scale aerial movements. We obtained wind data from NASA SeaWinds scatterometer to calculate wind cost (impedance) models reflecting the resistance to the aerial movement near the ocean surface. We also tracked the movements of a model organism, the Cory's shearwater (Calonectris diomedea), a pelagic bird known to perform long distance migrations. Cost models revealed that distant areas can be connected through “wind highways” that do not match the shortest great circle routes. Bird routes closely followed the low-cost “wind-highways” linking breeding and wintering areas. In addition, we found that a potential barrier, the near surface westerlies in the Atlantic sector of the Intertropical Convergence Zone (ITCZ), temporally hindered meridional trans-equatorial movements. Once the westerlies vanished, birds crossed the ITCZ to their winter quarters. This study provides a novel approach to investigate wind-mediated movements in oceanic environments and shows that large-scale migration and dispersal processes over the oceans can be largely driven by spatiotemporal wind patterns
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