| 221. |
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| 222. |
- Jackson, Chelsea L., et al.
(författare)
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Diagnostic and prognostic implications of a three-antibody molecular subtyping algorithm for non-muscle invasive bladder cancer
- 2022
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 8:2, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- Intrinsic molecular subtypes may explain marked variation between bladder cancer patients in prognosis and response to therapy. Complex testing algorithms and little attention to more prevalent, early-stage (non-muscle invasive) bladder cancers (NMIBCs) have hindered implementation of subtyping in clinical practice. Here, using a three-antibody immunohistochemistry (IHC) algorithm, we identify the diagnostic and prognostic associations of well-validated proteomic features of basal and luminal subtypes in NMIBC. By IHC, we divided 481 NMIBCs into basal (GATA3−/KRT5+) and luminal (GATA3+/KRT5 variable) subtypes. We further divided the luminal subtype into URO (p16 low), URO-KRT5+ (KRT5+), and genomically unstable (GU) (p16 high) subtypes. Expression thresholds were confirmed using unsupervised hierarchical clustering. Subtypes were correlated with pathology and outcomes. All NMIBC cases clustered into the basal/squamous (basal) or one of the three luminal (URO, URO-KRT5+, and GU) subtypes. Although uncommon in this NMIBC cohort, basal tumors (3%, n = 16) had dramatically higher grade (100%, n = 16, odds ratio [OR] = 13, relative risk = 3.25) and stage, and rapid progression to muscle invasion (median progression-free survival = 35.4 months, p = 0.0001). URO, the most common subtype (46%, n = 220), showed rapid recurrence (median recurrence-free survival [RFS] = 11.5 months, p = 0.039) compared to its GU counterpart (29%, n = 137, median RFS = 16.9 months), even in patients who received intravesical immunotherapy (p = 0.049). URO-KRT5+ tumors (22%, n = 108) were typically low grade (66%, n = 71, OR = 3.7) and recurred slowly (median RFS = 38.7 months). Therefore, a simple immunohistochemical algorithm can identify clinically relevant molecular subtypes of NMIBC. In routine clinical practice, this three-antibody algorithm may help clarify diagnostic dilemmas and optimize surveillance and treatment strategies for patients.
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| 223. |
- Jacquemin, Benedicte, et al.
(författare)
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Ambient Air Pollution and Adult Asthma Incidence in Six European Cohorts (ESCAPE)
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 613-621
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE: We aimed to investigate the association between air pollution and adult onset asthma. METHODS: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. RESULTS: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 mu g/m(3); p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 mu g/m(3); p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 mu g/m(3)), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 mu g/m(3)), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10(-5)/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles x meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 mu g/m(3)). CONCLUSIONS: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.
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| 224. |
- Jeliazkova, N, et al.
(författare)
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The eNanoMapper database for nanomaterial safety information
- 2015
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Ingår i: Beilstein journal of nanotechnology. - : Beilstein Institut. - 2190-4286. ; 6, s. 1609-1634
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NanoSafety Cluster, a cluster of projects funded by the European Commision, identified the need for a computational infrastructure for toxicological data management of engineered nanomaterials (ENMs). Ontologies, open standards, and interoperable designs were envisioned to empower a harmonized approach to European research in nanotechnology. This setting provides a number of opportunities and challenges in the representation of nanomaterials data and the integration of ENM information originating from diverse systems. Within this cluster, eNanoMapper works towards supporting the collaborative safety assessment for ENMs by creating a modular and extensible infrastructure for data sharing, data analysis, and building computational toxicology models for ENMs.Results: The eNanoMapper database solution builds on the previous experience of the consortium partners in supporting diverse data through flexible data storage, open source components and web services. We have recently described the design of the eNanoMapper prototype database along with a summary of challenges in the representation of ENM data and an extensive review of existing nano-related data models, databases, and nanomaterials-related entries in chemical and toxicogenomic databases. This paper continues with a focus on the database functionality exposed through its application programming interface (API), and its use in visualisation and modelling. Considering the preferred community practice of using spreadsheet templates, we developed a configurable spreadsheet parser facilitating user friendly data preparation and data upload. We further present a web application able to retrieve the experimental data via the API and analyze it with multiple data preprocessing and machine learning algorithms.Conclusion: We demonstrate how the eNanoMapper database is used to import and publish online ENM and assay data from several data sources, how the “representational state transfer” (REST) API enables building user friendly interfaces and graphical summaries of the data, and how these resources facilitate the modelling of reproducible quantitative structure–activity relationships for nanomaterials (NanoQSAR).
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| 225. |
- Jiang, Y. B., et al.
(författare)
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Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 88-102
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. Methods We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. Results We identified 429 proteins that were dysregulated in AD plasma. We selected 19 "hub proteins" representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690-0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. Discussion This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.
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| 226. |
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| 227. |
- Johnson, Candice, et al.
(författare)
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Skin sensitization in silico protocol
- 2020
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducing a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.
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| 228. |
- Kacmarcik, J., et al.
(författare)
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Unusual Interplay between Superconductivity and Field-Induced Charge Order in YBa2Cu3Oy
- 2018
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 121:16
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed study of the temperature (T) and magnetic field (H) dependence of the electronic density of states (DOS) at the Fermi level, as deduced from specific heat and Knight shift measurements in underdoped YBa2Cu3Oy. We find that the DOS becomes field independent above a characteristic field H-DOS, and that the H-DOS (T) line displays an unusual inflection near the onset of the long-range 3D charge-density wave order. The unusual S shape of H-DOS (T) is suggestive of two mutually exclusive orders that eventually establish a form of cooperation in order to coexist at low T. On theoretical grounds, such a collaboration could result from the stabilization of a pair-density wave state, which calls for further investigation in this region of the phase diagram.
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| 229. |
- Kall, M., et al.
(författare)
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Resonance Raman scattering as a probe of oxygen dynamics in YBa2Cu3Ox
- 1998
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Ingår i: Journal of Physics and Chemistry of Solids. - 0022-3697 .- 1879-2553. ; 59, s. 1988-1990
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Tidskriftsartikel (refereegranskat)abstract
- We report on the metastable photo-bleaching of the 2.15 eV yellow Raman resonance in oxygen deficient YBa2Cu3Ox (x = 6.35-6.87), extending investigations by Wake ct al. (Phys. Rev. Lett., 1991,67, 3728) for x approximate to 7. Polarization, x dependence and phonon spectra indicate that the resonance is localized at oxygen vacancies in long CuO-chains. The resonance is thermally reactivated from the metastable bleached state with a relaxation time tau similar to exp[Delta/k(B)T] with Delta approximate to 1 eV. The resulting temperature dependent equilibrium resonance intensity essentially miners the oxygen superstructure disordering around T* approximate to 100 degrees C observed in the same crystals by hard X-ray diffraction, thus offering a new effective probe of chain-oxygen dynamics in YBa2Cu3Ox. (C) 1998 Elsevier Science Ltd. All rights reserved.
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| 230. |
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