| 581. |
- Razzaq, M., et al.
(författare)
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Explainable Artificial Neural Network for Recurrent Venous Thromboembolism Based on Plasma Proteomics
- 2021
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Ingår i: Computational Methods in Systems Biology19th International Conference, CMSB 2021, Bordeaux, France, September 22–24, 2021, Proceedings. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 108-121
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Konferensbidrag (refereegranskat)abstract
- Venous thromboembolism (VTE) is the third most common cardiovascular disease, affecting ∼ 1,000,000 individuals each year in Europe. VTE is characterized by an annual recurrent rate of ∼ 6%, and ∼ 30% of patients with unprovoked VTE will face a recurrent event after a six-month course of anticoagulant treatment. Even if guidelines recommend life-long treatment for these patients, about ∼ 70% of them will never experience a recurrence and will receive unnecessary lifelong anti-coagulation that is associated with increased risk of bleeding and is highly costly for the society. There is then urgent need to identify biomarkers that could distinguish VTE patients with high risk of recurrence from low-risk patients. Capitalizing on a sample of 913 patients followed up for the risk of VTE recurrence during a median of ∼ 10 years and profiled for 376 plasma proteomic antibodies, we here develop an artificial neural network (ANN) based strategy to identify a proteomic signature that helps discriminating patients at low and high risk of recurrence. In a first stage, we implemented a Repeated Editing Nearest Neighbors algorithm to select a homogeneous sub-sample of VTE patients. This sub-sample was then split in a training and a testing sets. The former was used for training our ANN, the latter for testing its discriminatory properties. In the testing dataset, our ANN led to an accuracy of 0.86 that compared to an accuracy of 0.79 as provided by a random forest classifier. We then applied a Deep Learning Important FeaTures (DeepLIFT) – based approach to identify the variables that contribute the most to the ANN predictions. In addition to sex, the proposed DeepLIFT strategy identified 6 important proteins (DDX1, HTRA3, LRG1, MAST2, NFATC4 and STXBP5) whose exact roles in the etiology of VTE recurrence now deserve further experimental validations.
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| 582. |
- Robertson, Lindsay B, et al.
(författare)
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Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation
- 2010
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 9:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.
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| 583. |
- Roth, Lynn, et al.
(författare)
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Pharmacological modulation of vascular ageing: a review from VascAgeNet
- 2023
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Ingår i: Ageing Research Reviews. - 1872-9649.
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Forskningsöversikt (refereegranskat)abstract
- Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.
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| 584. |
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| 585. |
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| 586. |
- Saigal, Trishna, et al.
(författare)
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Poly(ethylene oxide) star polymer adsorption at the silica/aqueous interface and displacement by linear poly(ethylene oxide)
- 2013
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 29:12, s. 3999-4007
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Tidskriftsartikel (refereegranskat)abstract
- Multiarm star copolymers with approximately 460 poly(ethylene oxide) (PEO) arms that have a degree of polymerization N = 45 were synthesized via atom transfer radical polymerization (ATRP) of PEO-methacrylate macromonomers in the presence of divinyl benzene cross-linkers. These are an example of molecular or nanoparticulate brushes that are of interest as steric stabilizers or boundary lubrication agents when adsorbed from solution to a solid/aqueous interface. We use ellipsometry to measure adsorption isotherms at the silica/aqueous interface for PEO star polymers and linear PEO chains having molecular weights comparable either to the star polymer or to the individual arms. The compactness of the PEO star polymers (molecular weight 1.2 × 106) yields a saturation surface excess concentration that is approximately 3.5 times greater than that of the high molecular weight (1 × 106) linear PEO. Adsorption of low molecular weight (6000) linear PEO was below the detection limit. Competitive adsorption experiments were conducted with ellipsometry, complemented by independent quartz crystal microbalance with dissipation (QCM-D) measurements. Linear PEO (high molecular weight) displaced preadsorbed PEO star polymers over the course of approximately 1.5 h, to form a mixed adsorbed layer having not only a significantly lower overall polymer surface excess concentration, but also a significantly greater amount of hydrodynamically entrapped water. Challenging a preadsorbed linear PEO (high molecular weight) layer with PEO star polymers produced no measurable change in the overall polymer surface excess concentration, but changes in the QCM-D energy dissipation and resonance frequency suggested that the introduction of PEO star polymers caused a slight swelling of the layer with a correspondingly small increase in entrapped water content.
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| 587. |
- Silber, H., et al.
(författare)
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Lack of Replication or Generalization? Cultural Values Explain a Question Wording Effect
- 2022
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Ingår i: Journal of Survey Statistics and Methodology. - : Oxford University Press (OUP). - 2325-0984 .- 2325-0992. ; 10:5, s. 1121-1147
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Tidskriftsartikel (refereegranskat)abstract
- In the context of the current "replication crisis" across the sciences, failures to reproduce a finding are often viewed as discrediting it. This paper shows how such a conclusion can be incorrect. In 1981, Schuman and Presser showed that including the word "freedom" in a survey question significantly increased approval of allowing a speech against religion in the USA. New experiments in probability sample surveys (n = 23,370) in the USA and 10 other countries showed that the wording effect replicated in the USA and appeared in four other countries (Canada, Germany, Taiwan, and the Netherlands) but not in the remaining countries. The effect appeared only in countries in which the value of freedom is especially salient and endorsed. Thus, public support for a proposition was enhanced by portraying it as embodying a salient principle of a nation's culture. Instead of questioning initial findings, inconsistent results across countries signal limits on generalizability and identify an important moderator.
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| 588. |
- Stacey, Glyn N, et al.
(författare)
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Stem cell culture conditions and stability : a joint workshop of the PluriMes Consortium and Pluripotent Stem Cell Platform
- 2019
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Ingår i: Regenerative Medicine. - : Future Medicine Ltd. - 1746-0751 .- 1746-076X. ; 14:3, s. 243-255
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Human stem cells have the potential to transform medicine. However, hurdles remain to ensure that manufacturing processes produce safe and effective products. A thorough understanding of the biological processes occurring during manufacture is fundamental to assuring these qualities and thus, their acceptability to regulators and clinicians. Leaders in both human pluripotent and somatic stem cells, were brought together with experts in clinical translation, biomanufacturing and regulation, to discuss key issues in assuring appropriate manufacturing conditions for delivery of effective and safe products from these cell types. This report summarizes the key issues discussed and records consensus reached by delegates and emphasizes the need for accurate language and nomenclature in the scientific discourse around stem cells.
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| 589. |
- Stark, T. H., et al.
(författare)
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Generalization of Classic Question Order Effects Across Cultures
- 2020
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Ingår i: Sociological Methods & Research. - : SAGE Publications. - 0049-1241 .- 1552-8294. ; 49:3, s. 567-602
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Tidskriftsartikel (refereegranskat)abstract
- Questionnaire design is routinely guided by classic experiments on question form, wording, and context conducted decades ago. This article explores whether two question order effects (one due to the norm of evenhandedness and the other due to subtraction or perceptual contrast) appear in surveys of probability samples in the United States and 11 other countries (Canada, Denmark, Germany, Iceland, Japan, the Netherlands, Norway, Portugal, Sweden, Taiwan, and the United Kingdom;N= 25,640). Advancing theory of question order effects, we propose necessary conditions for each effect to occur, and found that the effects occurred in the nations where these necessary conditions were met. Surprisingly, the abortion question order effect even appeared in some countries in which the necessary condition was not met, suggesting that the question order effect there (and perhaps elsewhere) was not due to subtraction or perceptual contrast. The question order effects were not moderated by education. The strength of the effect due to the norm of evenhandedness was correlated with various cultural characteristics of the nations. Strong support was observed for the form-resistant correlation hypothesis.
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| 590. |
- Stoustrup, Peter, et al.
(författare)
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Management of orofacial manifestations of juvenile idiopathic arthritis : Interdisciplinary consensus-based recommendations.
- 2023
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 75:1, s. 4-14
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, dysfunction and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management.OBJECTIVES: 1) To develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA. 2) To create a future research agenda related to management of TMJ arthritis in children with JIA.METHODS: The recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during two consensus-meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: Pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study.RESULTS: Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to: diagnosis (n=4), treatment of TMJ arthritis (active TMJ inflammation) (n=2), treatment of TMJ dysfunction and symptoms (n=3), treatment of arthritis-related dentofacial deformity (n=2), and other related aspects to JIA (n=1). Additionally, a future interdisciplinary research agenda was developed.CONCLUSIONS: These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA. This article is protected by copyright. All rights reserved.
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